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| Name | Class |
|---|---|
| Hospital de Clinicas de Porto Alegre | OTHER |
| Hospital Nossa Senhora da Conceicao | OTHER |
| Irmandade Santa Casa de Misericórdia de Porto Alegre | OTHER |
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Disseminated histoplasmosis (DH) is one of the major AIDS-defining infections responsible for high mortality rates in HIV-infected patients. Liposomal amphotericin B (L-AmB) is considered the therapy of choice for AIDS-associated histoplasmosis.However, many patients in Latin America are still treated with high doses of deoxycholate amphotericin B (d-AmB) for long periods. These regimens are associated with toxicity and thus reduced efficacy. Therefore, a better treatment strategy is necessary to improve the activity of this amphotericin B treatment. Treatment with a high dose of L-AmB for short periods (rather than standard doses for longer periods) is a promising approach considering that the antifungal effect of amphotericin B depends on peak concentrations. This randomized open-label Phase II study aims to determinate and to compare the activity and safety of three L-AmB regimens, as induction therapy for DH in AIDS patients.
This is a prospective randomized non-comparative multicenter open label trial of induction therapy with LAmB for DH in AIDS patients, followed by oral therapy with itraconazole.
The sample size planned is 99 patients of both sexes, older than 18 years (33 patients per study arm), infected with HIV and with confirmed diagnosis for DH. This sample size considers 10% of dropout.
The study will be conducted in accordance with the Helsinki Declaration, as well as the Standards national and international Guidelines for Good Clinical Practices.
Eight research centres in Brazil will competitively recruit patients: Santa Casa de Misericórdia de Porto Alegre (Porto Alegre; Dr Alessandro C. Pasqualotto), Hospital de ClÃnicas de Porto Alegre (Porto Alegre; Dr Diego R. Falci), Hospital Nossa Senhora da Conceição (Porto Alegre; Dr Marineide Melo), Hospital de Doenças Tropicais (Goiânia; Dr Cassia S. de Miranda Godoy), Hospital São José de Doenças Infecciosas (Fortaleza; Dr Terezinha M. J. Silva Leitão), and Hospital Giselda Trigueiro (Natal, Dr Monica B. Bay), Hospital Universitário Osvaldo Cruz (Recife, Dr. Filipe Prohaska Batista) e Instituto de Infectologia EmÃlia Ribas (São Paulo, Dr. José Ernesto Vidal Bermudez).
AIDS patients with DH will be randomized to one of three study arms:
(i) single IV dose of 10 mg/kg of L-AmB; (ii) single IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; (iii) IV dose of 3 mg/kg of L-AmB for 2 weeks.
Induction therapy will be followed in all patients by oral therapy with itraconazole capsules at 400 mg/daily for a year, azole drug which is already therapy of choice for consolidation of histoplasmosis, according to national and international Guidelines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| single dose of L-AmB | Experimental | single IV dose of 10 mg/kg of L-AmB on day 1; |
|
| 2 doses of L-AmB | Experimental | IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; |
|
| 2 weeks of L-AmB | Active Comparator | IV dose of 3 mg/kg of L-AmB for 2 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| single dose of L-AmB | Drug | (i) single IV dose of 10 mg/kg of L-AmB on day 1; |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Response | Maximum daily temperature lower than 37.8 °C | day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Mortality | Mortality rates attributed to the cause of death that is not directly and only related to histoplasmosis | day 14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daiane Dalla Lana, PhD | Federal University of Health Science of Porto Alegre | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Irmandade da Santa Casa de Misericórdia de Porto Alegre | Porto Alegre | Rio Grande do Sul | 90020-090 | Brazil |
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| ID | Title | Description |
|---|---|---|
| FG000 | Single Dose of L-AmB | single IV dose of 10 mg/kg of L-AmB on day 1; n=40 |
| FG001 | 2 Doses of L-AmB | IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; n=39 |
| FG002 | 2 Weeks of L-AmB | IV dose of 3 mg/kg of L-AmB for 2 weeks. n=39 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Single Dose of L-AmB | single IV dose of 10 mg/kg of L-AmB on day 1; N=40 |
| BG001 | 2 Doses of L-AmB | IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; N=39 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | Clinical Response | Maximum daily temperature lower than 37.8 °C | Clinical response on day 14 was 84.0% for the single-dose L-AmB arm-(32/38-1 patient was excluded due to concomitant tuberculosis, and another was lost to follow-up), 69.0% (25/36) for the 2-dose L-AmB arm, with 3 patients being excluded from efficacy analysis (1 individual with central nervous system histoplasmosis, 1 patient with concomitant tuberculosis, and another patient lost to follow-up); in the control group, response rate was 74.0% (28/38), with 1 patient being lost to follow-up. | Posted | Count of Participants | Participants | day 14 |
|
14 days
Kidney and liver toxicity - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573726/pdf/ciad313.pdf
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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 | Single Dose of L-AmB | single IV dose of 10 mg/kg of L-AmB on day 1; | 4 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| KDIGO | Renal and urinary disorders | Non-systematic Assessment | Renal toxicity stage 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infusion related toxicity | Blood and lymphatic system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Alessandro C. Pasqualotto | Universidade Federal de Ciências da Saúde de Porto Alegre | 5551999951614 | pasqualotto@ufcspa.edu.br |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 24, 2021 | Feb 21, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006660 | Histoplasmosis |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D015658 | HIV Infections |
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| 2 doses of L-AmB | Drug | (ii) IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; |
|
|
| 2 weeks of L-AmB | Drug | (iii) IV dose of 3 mg/kg of L-AmB for 2 weeks. |
|
|
| BG002 | 2 Weeks of L-AmB | IV dose of 3 mg/kg of L-AmB for 2 weeks. N=39 |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| 2 Doses of L-AmB |
IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573726/pdf/ciad313.pdf |
| OG002 | 2 Weeks of L-AmB | IV dose of 3 mg/kg of L-AmB for 2 weeks. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10573726/pdf/ciad313.pdf |
|
|
| Secondary | Overall Mortality | Mortality rates attributed to the cause of death that is not directly and only related to histoplasmosis | Overall survival on day 14 were, respectively: 89.0% (34/38) (single-dose L-AmB-with 2 patients being excluded from efficacy analysis); 78.0% (29/37) (2-dose L-AmB arm-2 patients excluded from efficacy analysis); and 89.7% (35/38) (control group-1 patient excluded from efficacy analysis). | Posted | Count of Participants | Participants | day 14 |
|
|
|
| 38 |
| 1 |
| 38 |
| 34 |
| 38 |
| EG001 | 2 Doses of L-AmB | IV dose of 10 mg/kg of L-AmB on day 1, followed by 5 mg/kg of L-AmB on day 3; | 8 | 37 | 6 | 37 | 27 | 37 |
| EG002 | 2 Weeks of L-AmB | IV dose of 3 mg/kg of L-AmB for 2 weeks. | 3 | 38 | 4 | 38 | 34 | 38 |
| Hypokalemia | Renal and urinary disorders | Non-systematic Assessment | Serum potassium levels of <3.5 mg/dL on day 14 |
|
| Hemoglobin drop | Blood and lymphatic system disorders | Non-systematic Assessment | Hemoglobin dropped >2 g/dL by day 14 |
|
| Hypomagnesemia | Renal and urinary disorders | Non-systematic Assessment | Serum magnesium levels of <1.8 mg/dL |
|
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| 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 |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |