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| ID | Type | Description | Link |
|---|---|---|---|
| 10149 | Registry Identifier | DAIDS-ES | |
| ACTG A5225 | |||
| HiFLAC | |||
| A5225/HiFLAC | |||
| A5225 |
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Cryptococcal meningitis (CM) is an infection of the membranes covering the brain and spinal cord, caused by the fungus Cryptococcus neoformans. CM most often affects people with compromised immune systems, like those with advanced HIV infection. This study explored the safety, tolerability, and therapeutic effect of a new treatment regimen with high-dose fluconazole for management of CM in HIV-infected patients.
CM is the most common central nervous system (CNS) complication of AIDS worldwide and accounts for up to a third of all deaths from AIDS in many developing countries. Current treatments for CM are lacking in both effectiveness and accessibility, particularly in limited-resources settings. Conventional therapies utilizing an amphotericin B deoxycholate (ampho B)-based regimen require maintaining intravenous access (IV) and monitoring and treating any associated complications. The price to acquire ampho B can also be prohibitive to successful treatment. Cumulatively, a treatment course with ampho B is neither cost effective nor administratively efficient, leaving patients either untreated or inadequately treated with low-dose regimens of fluconazole alone.
Fluconazole is widely available, inexpensive, can be given orally, has a demonstrated safety profile over a broad range of doses, and has proven activity against the fungus that causes CM, Cryptococcus neoformans. All of these factors make fluconazole a potential treatment option for a wide range of people. However, at its present recommended dosage, fluconazole is only expected to be successful in 34% to 42% of patients. This rate is lower than regimens combining fluconazole with other treatments including flucytosine or ampho B.
The purpose of this study was to evaluate whether high-dose fluconazole is safe and effective for the treatment of CM for up to 10 weeks. This study also collected information about treating CM with ampho B (either alone or with another drug, either flucytosine or fluconazole).
For this study, 168 HIV-infected people with CM participated for a duration of 24 weeks. This study proceeded with 2 stages and each stage consisted of up to 4 steps. Participants could take part in only one stage of the study. Stage 1 measured the maximum tolerated dose (MTD) of fluconazole in participants. Stage 2 consisted of dose validation and safety monitoring.
In Stage 1, participants were randomly assigned to receive either fluconazole only or an ampho B-based regimen (a regimen that is either ampho B alone or ampho B in combination with 5-fluorocytosine or fluconazole, according to the local standard of care).Three doses of fluconazole were tested, and the MTD was found to be 2000 mg/day. The two higher doses of fluconazole tested in Stage 1 (1600 mg/day and 2000 mg/day doses) were tested further in Stage 2 of the study.
Participants enrolled in Stage 2 were randomly assigned to receive treatment with either fluconazole only (at one of the 2 doses (1600 mg/day or 2000 mg/day) found to be safe in Stage 1) or an ampho B-based regimen.
After randomization in Step 1, participants in both Stage 1 and Stage 2 could be enrolled in up to three additional steps. In Step 2, participants who were randomly assigned to receive the ampho B-based regimen and who were intolerant to the regimen (experienced a treatment limiting toxicity [TLT]) received fluconazole (400-800mg daily). Participants who received study-provided fluconazole in Step 1 or in Step 2 could be enrolled in Step 3 if they had a negative cerebrospinal fluid (CSF) culture. Participants in Step 3 received fluconazole (400mg daily) until Week 10. At Week 10, all participants were enrolled in Step 4 and received a daily dose of fluconazole of 200mg until the end of the study (Week 24). Participants in both stages beginning treatment with ampho B received daily ampho B intravenously for up to 2 weeks.
Before entering the study, potential participants attended a screening visit where they had CSF collected via lumbar puncture. HIV testing was also conducted, along with clinical assessments, and a health and medical history questionnaire. Participants had blood collection, an electrocardiogram (ECG), and a pregnancy test (if applicable) at that visit. Once accepted into the study, participants again answered questions about their health and medication history; had a complete physical exam, blood collection, HIV testing, neurological exam, lumbar puncture, and ECG; and may have had a pregnancy test (if applicable).
Study visits occurred during Weeks 1 (at Days 1, 4, and 7), 2, 4, 6, 8, 10, and 24, and extra visits could occur for individualized reasons. Total study duration was 24 weeks. Plasma, urine, serum, and CSF samples were collected from all participants and stored for possible future use.
Note on efficacy population versus safety population: After entering the study, participants had their CM diagnosis confirmed by testing of the CSF collected via lumbar puncture. Confirmation could take up to 2 weeks after study entry. Due to the mortality rate of CM, participants received treatment before CM diagnosis confirmation. Post-entry 12 participants either reported non-confirmatory baseline results making them ineligible. An additional 2 participants were found to be ineligible for the study but died prior to being found ineligible (one had non-confirmatory baseline results, one was on a disallowed medication) All participants (n=168) are included in the safety population. Participants who were ineligible after study entry were excluded from the efficacy population (n=16). The efficacy population had 154 participants. Outcomes will specify if the efficacy population is used instead of the safety population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Stage 1, Fluconazole 1200mg | Experimental | Participants receive Fluconazole 1200mg induction dose in Stage 1 |
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| Stage 1, Fluconazole 1600mg | Experimental | Participants receive Fluconazole 1600mg induction dose in Stage 1 |
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| Stage 1, Fluconazole 2000mg | Experimental | Participants receive Fluconazole 2000mg induction dose in Stage 1 |
|
| Stage 1, Ampho B | Active Comparator | Participants receive Amphotericin B followed by Fluconazole in Stage 1 |
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| Stage 2, Fluconazole 1600mg | Experimental | Participants receive Fluconazole 1600mg induction dose in Stage 2 |
|
| Stage 2, Fluconazole 2000mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fluconazole | Drug | Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Discontinued Study-provided High Dose Fluconazole or Ampho B | Discontinuation of study-provided high dose fluconazole at or by week 10 Discontinuation of study-provided ampho B at or by week 2 Discontinuation includes discontinuing for any reason, including progression of symptoms, death, etc. | Measured from study entry through Week10 |
| Categorized Quantitative Culture Results | Count of participants who were CM negative (had no cryptococcal growth), CM negative after switching treatment (switched from Fluconazole to Ampho B or vice versa and later became CM negative), CM positive, Died, Lost to follow-up. Note: CM positive means continued to have cryptococcal growth. | At entry, Week 2, and Week 10 |
| Change in Log10 Quantitative CSF Culture Results | Change in quantitative CSF (cerebrospinal fluid) cultures. Note: No further CSF specimens are drawn following a negative culture. Thus, only week 2 CSF cultures are considered in this analysis. | Entry and Week 2 |
| Kaplan Meier (KM) Proportion of Participant Mortality | Kaplan Meier Proportion of participants who died over study with 90% Confidence Intervals. | Measured from study entry through Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Results of the Neurological Examination | Results from Glasgow Coma Score, which provides assessment of impairment of conscious level in response to defined stimuli. Min score of 0 and max score of 15 (no mental impairment). | Measured at study entry, Week 2, and Week 10 |
| Results of Functional Status Evaluation |
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Inclusion Criteria - Step 1
Exclusion Criteria - Step 1
Inclusion Criteria - Step 2
Exclusion Criteria - Step 2
Inclusion Criteria - Step 3
Exclusion Criteria - Step 3
Inclusion Criteria - Step 4
- On study treatment at Week 10 (Days 63-77) with no plans to discontinue study treatment
Exclusion Criteria - Step 4
- Currently off study treatment
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| Name | Affiliation | Role |
|---|---|---|
| Umesh G. Lalloo, MD, FRCP | Nelson R. Mandela School of Medicine | Study Chair |
| Robert A. Larsen, MD | USC School of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California CRS | Los Angeles | California | 90033-1079 | United States | ||
| Byramjee Jeejeebhoy Medical College (BJMC) CRS |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19365271 | Background | Bicanic T, Meintjes G, Rebe K, Williams A, Loyse A, Wood R, Hayes M, Jaffar S, Harrison T. Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study. J Acquir Immune Defic Syndr. 2009 Jun 1;51(2):130-4. doi: 10.1097/QAI.0b013e3181a56f2e. | |
| 19345042 | Background |
| Label | URL |
|---|---|
| DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004; Clarification, August 2009 | View source |
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The study opened on February 19, 2010. The first participant enrolled on April 16, 2010. Stage 1 closed on September 5, 2013. A5225 Stage 2 opened on September 15, 2014 and the first participant enrolled on February 2, 2015. Stage 2 closed on August 19, 2016. Ten sites enrolled participants (1 domestic, 9 international).
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| ID | Title | Description |
|---|---|---|
| FG000 | Stage 1, Fluconazole 1200mg | Participants receive Fluconazole 1200mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Phase 1 was the dose escalation phase which used a sequential model. Phase 2 was the dose validation phase which used a parallel model. Analyses combine arms from Phase 1 and Phase 2, as appropriate, for validation.
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Participants receive Fluconazole 2000mg induction dose in Stage 2
|
| Stage 2, Ampho B | Active Comparator | Participants receive Amphotericin B followed by Fluconazole in Stage 2 |
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| Amphotericin B | Drug | Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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Functional assessment of work status and ability. Consists of 2 measures: 1) Does participants have full time work status 2) Does participant have functional ability to work. The measure from 6 week before enrollment will be referred to as 'baseline'. |
| Measured 6 weeks before enrollment, at study entry, at Week 10, and at Week 24 |
| Length of Hospitalization | Duration of first hospitalization in days starting at entry in safety population. | Measured from study entry through Week 10 |
| Number of Hospital Admissions | Count of number of times a participant was admitted to the hospital. | Measured from study entry through Week 24 |
| Number of Participants With Progression of Symptoms | Progression of symptoms is defined as:
| Measured from study entry through Week 24 |
| Number of Participants With CNS IRIS | Number of participants who were diagnosed with CNS immune reconstitution inflammatory syndrome (IRIS) | Measured from study entry through Week 24 |
| Number of Participants With Grade 3 and 4 Adverse Events | Occurrence of grade 3 (severe) and 4 (life-threatening) sign and symptoms events (as defined by FSTRF Appendix 29) Occurrence of grade 3 (severe) and 4 (life-threatening) laboratory events (as defined by FSTRF Appendix 76) See DAIDS AE Grading table V1.0 | Measured from study entry through Week 24 |
| Pune |
| Maharashtra |
| 411001 |
| India |
| Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS | Kericho | Rift Valley | 20200 | Kenya |
| Moi University Clinical Research Center (MUCRC) CRS | Eldoret | 30100 | Kenya |
| San Miguel CRS | Lima | 32 | Peru |
| Wits Helen Joseph Hospital CRS (Wits HJH CRS) | Johannesburg | Gauteng | 2092 | South Africa |
| Durban International Clinical Research Site CRS | Durban | KwaZulu-Natal | 4013 | South Africa |
| Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS | Chiang Mai | 50200 | Thailand |
| Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site | Kampala | Uganda |
| Parirenyatwa CRS | Harare | Zimbabwe |
| Pappalardo MC, Szeszs MW, Martins MA, Baceti LB, Bonfietti LX, Purisco SU, Baez AA, Melhem MS. Susceptibility of clinical isolates of Cryptococcus neoformans to amphotericin B using time-kill methodology. Diagn Microbiol Infect Dis. 2009 Jun;64(2):146-51. doi: 10.1016/j.diagmicrobio.2009.02.007. Epub 2009 Apr 2. |
| 19304977 | Background | Seddon J, Mangeya N, Miller RF, Corbett EL, Ferrand RA. Recurrence of cryptococcal meningitis in HIV-infected patients following immune reconstitution. Int J STD AIDS. 2009 Apr;20(4):274-5. doi: 10.1258/ijsa.2008.008312. |
| 36780493 | Derived | Lalloo UG, Komarow L, Aberg JA, Clifford DB, Hogg E, McKhann A, Bukuru A, Lagat D, Pillay S, Mave V, Supparatpinyo K, Samaneka W, Langat D, Ticona E, Badal-Faesen S, Larsen RA; ACTG A5225 Team. Higher Dose Oral Fluconazole for the Treatment of AIDS-related Cryptococcal Meningitis (HIFLAC)-report of A5225, a multicentre, phase I/II, two-stage, dose-finding, safety, tolerability and efficacy randomised, amphotericin B-controlled trial of the AIDS Clinical Trials Group. PLoS One. 2023 Feb 13;18(2):e0281580. doi: 10.1371/journal.pone.0281580. eCollection 2023. |
| Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010 | View source |
| FG001 | Stage 1, Fluconazole 1600mg | Participants receive Fluconazole 1600mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| FG002 | Stage 1, Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| FG003 | Stage 1, Ampho B | Participants receive Amphotericin B followed by Fluconazole in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
| FG004 | Stage 2, Fluconazole 1600mg | Participants receive Fluconazole 1600mg induction dose in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| FG005 | Stage 2, Fulconazole 2000mg | Participants receive Fluconazole 2000mg induction dose in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| FG006 | Stage 2, Ampho B | Participants receive Amphotericin B followed by Fluconazole in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Stage 1, Fluconazole 1200mg | Participants receive Fluconazole 1200mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| BG001 | Stage 1, Fluconazole 1600mg | Participants receive Fluconazole 1600mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| BG002 | Stage 1, Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| BG003 | Stage 1, Ampho B | Participants receive Amphotericin B followed by Fluconazole in Stage 1 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
| BG004 | Stage 2, Fluconazole 1600mg | Participants receive Fluconazole 1600mg induction dose in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| BG005 | Stage 2, Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| BG006 | Stage 2, Ampho B | Participants receive Amphotericin B followed by Fluconazole in Stage 2 Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Weight | Median | Inter-Quartile Range | kilograms |
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| BMI (Body Mass Index) | Median | Inter-Quartile Range | kg/m^2 |
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| CD4+ | Count of Participants | Participants |
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| HIV-1 RNA | Median | Inter-Quartile Range | log10(copies/mL) |
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| Glasgow Coma Score | The Glasgow Coma Score provides an assessment of impairment of conscious level in response to defined stimuli. The GCS is on a scale from 0=worst to 15=best. | One participant missing baseline Glasgow Coma Score. | Count of Participants | Participants |
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| Quantitative Cryptococcal Meningitis Culture | Median | Inter-Quartile Range | Log10 CFU/mL |
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| Anti-Retroviral Therapy (ART) Status | Count of Participants | Participants |
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| Opportunistic Infections | Count of Participants | Participants |
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| Mini Mental Status | The Mini Mental Status is a 26-point questionnaire that is used to measure cognitive impairment. Scale is 0=worst to 26=best. | Not all participants were able to complete a Mini Mental Status at baseline. | Median | Inter-Quartile Range | Scores on a scale |
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| Opening Pressure (from Lumbar Pucture) | Not all participants were able to have a lumbar puncture at entry. | Median | Inter-Quartile Range | mm H20 |
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| White Blood Cell count (from CSF) | Not all participants were able to have a lumbar puncture. Of those that did, not all were able to have enough fluid collected for WBC count. | Median | Inter-Quartile Range | cells/mm^3 |
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| Albumin | Not all participants had an albumin measurement. | Median | Inter-Quartile Range | g/dL |
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| ALT (Alanine Aminotransferase) | Median | Inter-Quartile Range | U/L |
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| Creatinine Clearance | Mean | Inter-Quartile Range | mL/min |
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| Cryptococcal Antigen (CrAG) Titer | Not all participants had a CrAG titer observed at baseline. | Median | Inter-Quartile Range | titers |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Discontinued Study-provided High Dose Fluconazole or Ampho B | Discontinuation of study-provided high dose fluconazole at or by week 10 Discontinuation of study-provided ampho B at or by week 2 Discontinuation includes discontinuing for any reason, including progression of symptoms, death, etc. | Analysis in safety population (see study detailed description for details) | Posted | Count of Participants | Participants | Measured from study entry through Week10 |
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| Primary | Categorized Quantitative Culture Results | Count of participants who were CM negative (had no cryptococcal growth), CM negative after switching treatment (switched from Fluconazole to Ampho B or vice versa and later became CM negative), CM positive, Died, Lost to follow-up. Note: CM positive means continued to have cryptococcal growth. | Arms pooled by dose. Analysis in efficacy population (see study detailed description for details). | Posted | Count of Participants | Participants | At entry, Week 2, and Week 10 |
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| Primary | Change in Log10 Quantitative CSF Culture Results | Change in quantitative CSF (cerebrospinal fluid) cultures. Note: No further CSF specimens are drawn following a negative culture. Thus, only week 2 CSF cultures are considered in this analysis. | Arms pooled by dose. Analysis done in efficacy population (see study detailed description for details). Excludes participants who did not have a week 2 observation. | Posted | Median | Inter-Quartile Range | Log10 CFU/mL | Entry and Week 2 |
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| Primary | Kaplan Meier (KM) Proportion of Participant Mortality | Kaplan Meier Proportion of participants who died over study with 90% Confidence Intervals. | Arms pooled by dose in the safety population (see study detailed description for details). | Posted | Number | 90% Confidence Interval | proportion of participants | Measured from study entry through Week 24 |
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| Secondary | Results of the Neurological Examination | Results from Glasgow Coma Score, which provides assessment of impairment of conscious level in response to defined stimuli. Min score of 0 and max score of 15 (no mental impairment). | Arms pooled by dose. Safety population (see study detailed description for details). | Posted | Count of Participants | Participants | Measured at study entry, Week 2, and Week 10 |
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| Secondary | Results of Functional Status Evaluation | Functional assessment of work status and ability. Consists of 2 measures: 1) Does participants have full time work status 2) Does participant have functional ability to work. The measure from 6 week before enrollment will be referred to as 'baseline'. | Arms pooled by dose. Safety population (see study detailed description for details). | Posted | Count of Participants | Participants | Measured 6 weeks before enrollment, at study entry, at Week 10, and at Week 24 |
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| Secondary | Length of Hospitalization | Duration of first hospitalization in days starting at entry in safety population. | Arms pooled by dose in safety population (see study detailed description for details). Fluconazole 2000mg arm had one participant data missing (was not admitted to hospital at study entry). | Posted | Median | Inter-Quartile Range | Days | Measured from study entry through Week 10 |
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| Secondary | Number of Hospital Admissions | Count of number of times a participant was admitted to the hospital. | Arms pooled by dose in safety population (see study detailed description for details). | Posted | Count of Participants | Participants | Measured from study entry through Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Progression of Symptoms | Progression of symptoms is defined as:
| Arms pooled by dose. Analysis done in efficacy population (see detailed study description for details). | Posted | Count of Participants | Participants | Measured from study entry through Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With CNS IRIS | Number of participants who were diagnosed with CNS immune reconstitution inflammatory syndrome (IRIS) | Arms pooled by dose in study population (see study detailed description for details). | Posted | Count of Participants | Participants | Measured from study entry through Week 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Grade 3 and 4 Adverse Events | Occurrence of grade 3 (severe) and 4 (life-threatening) sign and symptoms events (as defined by FSTRF Appendix 29) Occurrence of grade 3 (severe) and 4 (life-threatening) laboratory events (as defined by FSTRF Appendix 76) See DAIDS AE Grading table V1.0 | Arms pooled by dose in safety population (see study detailed description for details). | Posted | Count of Participants | Participants | Measured from study entry through Week 24 |
|
Adverse event data were collected from study entry until end of study (24 weeks).
The protocol required reporting of all Grade >= 3 signs/symptoms, all Grade >= 2 laboratory toxicities, all estimated creatinine clearance values, and all signs/symptoms or laboratory toxicities that lead to a change in treatment, regardless of grade, were recorded. All diagnoses were recorded.
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (http://rsc.tech-res.com/safetyandpharmacovigilance/)
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stage 1: 1200mg Fluconazole | Participants receive Fluconazole 1200mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. | 9 | 22 | 14 | 22 | 22 | 22 |
| EG001 | Stage 1: 1600mg Fluconazole | Participants receive Fluconazole 1600mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. | 7 | 26 | 13 | 26 | 26 | 26 |
| EG002 | Stage 1: 2000mg Fluconazole | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. | 8 | 24 | 13 | 24 | 24 | 24 |
| EG003 | Stage 1: Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight | 7 | 24 | 11 | 24 | 24 | 24 |
| EG004 | Stage 2: 1600mg Fluconazole | Participants receive Fluconazole 1600mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. | 7 | 24 | 10 | 24 | 24 | 24 |
| EG005 | Stage 2: 2000mg Fluconazole | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. | 8 | 24 | 12 | 24 | 24 | 24 |
| EG006 | Stage 2: Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight | 4 | 24 | 6 | 24 | 24 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Peptic ulcer | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Death | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Immune reconstitution inflammatory syndrome | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cerebral toxoplasmosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Disseminated cryptococcosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Disseminated tuberculosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Malaria | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Meningitis bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Meningitis cryptococcal | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Immune reconstitution inflammatory syndrome associated Kaposi's sarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Kaposi's sarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Intracranial pressure increased | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Superior sagittal sinus thrombosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Conjunctival hyperaemia | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Anorectal swelling | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Oral disorder | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Cerebral toxoplasmosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Encephalitis cytomegalovirus | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Malaria | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Meningitis cryptococcal | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Meningitis tuberculous | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Pulmonary tuberculosis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Tuberculosis gastrointestinal | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood glucose decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood magnesium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood phosphorus decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood potassium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Blood sodium decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Micturition urgency | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rales | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Prurigo | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| ACTG Clinicaltrials.gov Coordinator | ACTG Network Coordinating Center, Social and Scientific Systems, Inc. | (301) 628-3313 | ACTGCT.Gov@s-3.com |
| ID | Term |
|---|---|
| D016919 | Meningitis, Cryptococcal |
| D015658 | HIV Infections |
| D008581 | Meningitis |
| ID | Term |
|---|---|
| D016921 | Meningitis, Fungal |
| D020314 | Central Nervous System Fungal Infections |
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D003453 | Cryptococcosis |
| D002494 | Central Nervous System Infections |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D000090862 | Neuroinflammatory Diseases |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D015725 | Fluconazole |
| D000666 | Amphotericin B |
| C059765 | amphotericin B, deoxycholate drug combination |
| C068538 | liposomal amphotericin B |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
Not provided
Not provided
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| Hispanic (regardless of Race) |
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| Asian, Pacific Islander |
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| South Africa |
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| Uganda |
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| Zimbabwe |
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| Kenya |
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| Thailand |
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| Peru |
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| India |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
|
|
|
| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
|
|
|
| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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Participants receive Fluconazole 1600mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| OG002 | Fluconazole 2000mg | Participants receive Fluconazole 2000mg induction dose Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. |
| OG003 | Ampho B | Participants receive Amphotericin B followed by Fluconazole Fluconazole: Step 1: [For participants randomized to Fluconazole] Induction dose of daily treatment of fluconazole given orally (adjusted according to weight). Step 2: [For participants randomized to Ampho B only] If participant is intolerant to Ampho B, participant transitions to fluconazole dosage of 400-800mg daily given orally. Step 3: If participant has a negative culture before week 10, participant transitions to consolidation therapy at dosage of 400mg daily given orally. Step 4: At week 10, participant transitions to maintenance therapy at dosage of 200mg daily given orally. Amphotericin B: Step 1: [For participants randomized to Ampho B] Ampho B given intravenously for approximately 2 weeks at a dosage of 0.7 to 1.0 mg/kg, dependent on a participant's weight |
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| CM Negative |
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| CM Negative after switching treatment |
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| Died |
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| Lost to Follow-up |
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| CM Negative |
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| CM Negative after switching treatment |
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| Died |
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| Lost to Follow-up |
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| Score = 15 |
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| Title | Measurements |
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| Score < 15 |
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| Score = 15 |
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| Title | Measurements |
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| Score < 15 |
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| Score = 15 |
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