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| ID | Type | Description | Link |
|---|---|---|---|
| U01AI125003 | U.S. NIH Grant/Contract | View source | |
| 33238 | Other Identifier | DAIDS-ES ID |
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SAEs with n=1 serotonin syndrome, n=2 SAEs after sertraline interruption.
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| Name | Class |
|---|---|
| Infectious Diseases Institute, Uganda | OTHER |
| National Institute of Allergy and Infectious Diseases (NIAID) | NIH |
| Mbarara University of Science and Technology | OTHER |
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Cryptococcal meningitis or "Crypto" is a life threatening fungal infection around the brain that requires hospitalization for treatment for 14 days and then continued therapy. Crypto causes 15-20% of HIV/AIDS-related deaths worldwide. However, this infection can be detected before one develops symptoms and becomes ill. People can be screened for infection by a blood test to detect "cryptococcal antigen," (called CrAg), which is part of the fungus, in blood. The World Health Organization and over 22 countries worldwide recommend CrAg screening of all persons with advanced AIDS entering or re-entering into HIV care.
However, it is not known how best to treat people with cryptococcal antigen in their blood, who don't otherwise yet have symptoms of infection around their brain. If no treatment is given, almost all people will develop infection of the brain and/or die. International guidelines suggest using both HIV medicines and an anti-fungal medicine, called fluconazole, to treat this early infection. However, despite this treatment approximately 1 in 4 people may get sick and/or die.
Researchers have recently discovered another medicine that may work against the Cryptococcus fungus. This medicine is called Sertraline, and it is actually a medicine that has been used for more than 25 years to treat depression (sadness). Sertraline is one of the most commonly used medicines worldwide.
The purpose of this research clinical trial is to determine if standard fluconazole antifungal therapy plus a high dose of Sertraline, will be better than standard fluconazole therapy alone for treating early disseminated cryptococcal infection in persons who are asymptomatic and do not yet have infection of the brain (i.e. meningitis).
This study seeks to test if Sertraline will improve survival through 6-months. Prior studies have shown that >90% of those who survive 6-months will survive >5 years.
This is a double-blind, randomized placebo-controlled clinical trial testing sertraline as an antifungal medicine in combination with fluconazole for treatment of HIV-infected persons with AIDS and asymptomatic cryptococcal antigenemia (CrAg+).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sertraline | Experimental | Fluconazole Standard of Care + Sertraline |
|
| Control | Placebo Comparator | Fluconazole Standard of Care + Placebo Oral Tablet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sertraline | Drug | sertraline 400mg/day |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 6 Month Meningitis-free Survival | Cryptococcal meningitis free survival with retention-in-care through 6 months
| 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 6-month Survival | Survival through 6 months | 6 months |
| Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis | Cumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Adherence to Study Drug | Participants' percent adherence to study drug regiment by pharmacy medication counts, representing the percent of the total prescribed medication taken by participants. | 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth K Nalintya, MBChB MPH | Infectious Disease Institute | Study Director |
| Radha Rajasingham, MD | University of Minnesota | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Infectious Disease Institute, Makerere University | Kampala | 22418 | Uganda |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32415846 | Result | Boulware DR, Nalintya E, Rajasingham R, Kirumira P, Naluyima R, Turya F, Namanda S, Rutakingirwa MK, Skipper CP, Nikweri Y, Hullsiek KH, Bangdiwala AS, Meya DB. Adjunctive sertraline for asymptomatic cryptococcal antigenemia: A randomized clinical trial. Med Mycol. 2020 Nov 10;58(8):1037-1043. doi: 10.1093/mmy/myaa033. |
| Label | URL |
|---|---|
| PreventCrypto.org has information and training materials for cryptococcal antigen screening and treatment | View source |
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A formal written data sharing plan exists. Protocol and trial documents can be shared. De-identified data can be shared after trial completion.
Available for at least 5 years
Upon request to the Principal Investigator
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| ID | Title | Description |
|---|---|---|
| FG000 | Sertraline | Fluconazole Standard of Care + Sertraline Sertraline: sertraline 400mg/day Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
| FG001 | Control | Fluconazole Standard of Care + Placebo Oral Tablet Placebo Oral Tablet: matched placebo tablet Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Sertraline | Fluconazole Standard of Care + Sertraline Sertraline: sertraline 400mg/day Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
| BG001 | Control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | 6 Month Meningitis-free Survival | Cryptococcal meningitis free survival with retention-in-care through 6 months
| Posted | Count of Participants | Participants | 6 months |
|
Through week 24
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sertraline | Fluconazole Standard of Care + Sertraline Sertraline: sertraline 400mg/day Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Gastrointestinal bleeding | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
Trial was terminated early by the NIAID DSMB for excess harm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Boulware | University of Minnesota | 612-624-1966 | boulw001@umn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 10, 2017 | Jul 24, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 6, 2017 | Jul 24, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003453 | Cryptococcosis |
| D017088 | AIDS-Related Opportunistic Infections |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D015658 | HIV Infections |
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| ID | Term |
|---|---|
| D020280 | Sertraline |
| D015725 | Fluconazole |
| ID | Term |
|---|---|
| D015057 | 1-Naphthylamine |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009281 | Naphthalenes |
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| Placebo Oral Tablet | Drug | matched placebo tablet |
|
|
| Fluconazole | Drug | Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
|
|
| 6 months |
| Number of Clinical Adverse Events (Grade 3-5) | Number of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months | 6 months |
| Number of Laboratory Grade 3-5 Adverse Events | Number of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale | 6 months |
| All-Cause Premature Study Drug/Placebo Discontinuation | Number of participants whose study drug/placebo use was halted prematurely due to any cause through 6 months | 6 months |
| Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time | Prevalence of depression by Patient Health Questionnaire (PHQ-9) over 6 months as measured at baseline, 4 weeks, 8 weeks, and 12 weeks. The PHQ-9 is a 9-item instrument for screening, diagnosing, monitoring, and measuring the severity of depression. Items are rated on a scale from 0 (not at all) to 3 (nearly every day). Total score is a sum of 9 item scores (Range 0-27). Greater scores indicate greater depressive symptoms. PHQ-9 scores of: 0-4 Minimal/No depression; 5-9 Mild depression; 10-14 Moderate depression; 15-19 Moderate severe depression; 20-27 Severe depression. This endpoint reports the median (interquartile range) of the PHQ-9 scores over time. | 12 weeks |
Fluconazole Standard of Care + Placebo Oral Tablet Placebo Oral Tablet: matched placebo tablet Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| On Antiretroviral Therapy (ART) at Radomization | Count of Participants | Participants |
|
| CD4 Cell Count | Median | Full Range | cells/mm3 |
|
|
|
| Secondary | 6-month Survival | Survival through 6 months | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Cumulative Incidence of Symptomatic Cryptococcal Meningoencephalitis | Cumulative incidence of symptomatic cryptococcal meningoencephalitis through 6 months | Posted | Number | meningitis events | 6 months |
|
|
|
| Secondary | Number of Clinical Adverse Events (Grade 3-5) | Number of Clinical Adverse Events by Division of AIDS (DAIDS) Scale for Grade 3-5 events through 6 months | Posted | Number | number of grade 3-5 adverse events | 6 months |
|
|
|
| Secondary | Number of Laboratory Grade 3-5 Adverse Events | Number of Laboratory Grade 3-5 Adverse Events through 6 months as per the Division of AIDS (DAIDS) grading scale | Posted | Number | number of grade 3-5 adverse events | 6 months |
|
|
|
| Secondary | All-Cause Premature Study Drug/Placebo Discontinuation | Number of participants whose study drug/placebo use was halted prematurely due to any cause through 6 months | Posted | Count of Participants | Participants | 6 months |
|
|
|
| Secondary | Prevalence of Depression by Patient Health Questionnaire (PHQ-9) Over Time | Prevalence of depression by Patient Health Questionnaire (PHQ-9) over 6 months as measured at baseline, 4 weeks, 8 weeks, and 12 weeks. The PHQ-9 is a 9-item instrument for screening, diagnosing, monitoring, and measuring the severity of depression. Items are rated on a scale from 0 (not at all) to 3 (nearly every day). Total score is a sum of 9 item scores (Range 0-27). Greater scores indicate greater depressive symptoms. PHQ-9 scores of: 0-4 Minimal/No depression; 5-9 Mild depression; 10-14 Moderate depression; 15-19 Moderate severe depression; 20-27 Severe depression. This endpoint reports the median (interquartile range) of the PHQ-9 scores over time. | Posted | Median | Inter-Quartile Range | score on a scale | 12 weeks |
|
|
|
| Other Pre-specified | Adherence to Study Drug | Participants' percent adherence to study drug regiment by pharmacy medication counts, representing the percent of the total prescribed medication taken by participants. | Posted | Median | Inter-Quartile Range | Percent of total prescribed medication t | 12 weeks |
|
|
|
| 0 |
| 11 |
| 4 |
| 11 |
| 4 |
| 11 |
| EG001 | Control | Fluconazole Standard of Care + Placebo Oral Tablet Placebo Oral Tablet: matched placebo tablet Fluconazole: Standard of Care Fluconazole per World Health Organization and Ugandan Guidelines (800mg/day x 2 weeks, 400mg/day x10 weeks, 200mg through 6 months). | 1 | 11 | 3 | 11 | 1 | 11 |
| Mania with Psychotic Disorder | Psychiatric disorders | Systematic Assessment |
|
| Pulmonary Embolism | Vascular disorders | Systematic Assessment |
|
| Meningitis | Nervous system disorders | Systematic Assessment | Meningitis complicated by CSF leak |
|
| Psychosis with Serotonin Syndrome | Nervous system disorders | Systematic Assessment |
|
| Death | Infections and infestations | Systematic Assessment | Death due to probable meningitis |
|
| Leukopenia | Immune system disorders | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
|
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| D000086982 |
| Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D009894 | Opportunistic Infections |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D011084 |
| Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Week 12 |
|
| Week 8 |
|
| Week 12 |
|