AmB Dose for Cryptococcal Meningitis

Study Overview
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Brief Summary
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Cryptococcal meningitis (CM) is one of the leading opportunistic infections and one of the most common causes of death in AIDS patients. Amphotericin B (AmB) is the corner stone in CM treatment. The effect of AmB was dose-dependent. Recent retrospective study indicated that longer duration rather than higher dose of AmB is necessary to reduce the mortality of CM. We aimed to explore the efficacy and safety of small dose but longer duration of AmB for the treatment of HIV-associated CM.

Official Title
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Antifungal Treatment of Cryptococcal Meningitis

Conditions
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Cryptococcal Meningitis, HIV Infections

Intervention / Treatment
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* Drug: Amphotericin B
* Drug: Flucytosine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV infection Naive to antiretroviral therapy Cryptococcal antigen, smear or culture positive in cerebrospinal fluid Agree to participate the study Exclusion Criteria: Having receiving antifungal treatment for ≥3 days ALT or AST > 5* upper limit of detection (ULD), or neutrophil< 0.5*10E9 cells/L, or hemoglobin < 90g/L or platelet <50*10E9/L or serum creatinine > ULD Pregnancy or breastfeeding Concomitant medications that are contraindicated with any research drug Any other contraindications for using amphotericin B or 5FC Inability to follow-up as accessed by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trial<br>Amphotericin B 0.5 mg/kg IVGTT QD + Flucytosine 100mg/kg PO QD for 4 weeks | Drug: Amphotericin B<br>* The trial group and the control group received AmB 0.5mg/kg for 4 weeks and 0.7mg/kg for 2 weeks respectively.<br>* Other names: Antiretroviral therapy;Drug: Flucytosine<br>* The trial group and the control group received 100mg/kg for 4 weeks and for 2 weeks respectively.<br>|
| Active Comparator: Control<br>Amphotericin B 0.7 mg/kg IVGTT QD + Flucytosine 100mg/kg PO QD for 2 weeks | Drug: Amphotericin B<br>* The trial group and the control group received AmB 0.5mg/kg for 4 weeks and 0.7mg/kg for 2 weeks respectively.<br>* Other names: Antiretroviral therapy;Drug: Flucytosine<br>* The trial group and the control group received 100mg/kg for 4 weeks and for 2 weeks respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects died at weeks 48 | Mortality in intent to treat population | 48 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with CSF culture positive for Cryptococcus at weeks 2 | Antifungal Activity | 2 weeks after randomization | 
| Number of subjects with disability at weeks 48 | Disability rate in intent to treat population | 48 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infection, Cryptococcal Meningitis, Amphotericin B