Three Induction Treatments on Cryptococcal Meningitis

Study Overview
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Brief Summary
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Three induction treatment strategies [ voriconazole +5FC vs. amphotericin deoxycholate (0.4-0.5 mg/kg/d)+5FC vs. amphotericin deoxycholate (0.7-1.0 mg/kg/d)+5FC ] for HIV-infected patients with cryptococcal meningitis were compared.

Detailed Description
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HIV-associated cryptococcal meningitis were randomly allocated into three induction treatment as follow: 1) 14 days of voriconazole 200mg bid +5FC, 2) 28 days of amphotericin deoxycholate (0.4-0.5 mg/kg/d) +5FC ; 3）14 days of deoxycholate (0.7-1 mg/kg/d) +5FC). After induction treatment were finished, all groups switched into fluconazole(400mg/d) for two-month consolidation treatment. 14-day early fungicidal rate, 90-day mortality, side effects , and tolerances were compared between three groups.

Official Title
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The Effect and Safety of Three Initial Introduction Treatments on HIV-infected Patients With Cryptococcal Meningitis: A Multi-center, Random and Prospective Study

Conditions
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HIV/AIDS, Cryptococcal Meningitis

Intervention / Treatment
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* Drug: Voriconazole 200mg
* Drug: amphotericin B deoxycholate (0.4-0.5mg/kg/d)
* Drug: Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of HIV infection; newly diagnosed Cryptococcal Meningitis by positive India ink staining or culture result, or both in cerebrospinal fluid (CSF); Anti-viral treatment naïve patients anti-fungal treatment naïve patients Exclusion Criteria: hepatitis virus co-infection; liver cirrhosis; congestive heart failure; chronic renal disorders; chronic obstructive pulmonary disease (COPD); Tuberculosis co-infection; malignances severe mental and neurological diseases Women during pregnancy and lactation intraveneous drug user (IDU) patients with follow abnormal test results:hemoglobin < 6 g/dl, white blood cell count < 2000 / μl, neutrophil count < 1000 / μl, platelet count < 75000 / μl, blood amylase > 3 times normal level Upper limit, serum creatinine > 1.5 times normal upper limit, aspartate aminotransferase / alanine aminotransferase / alkaline phosphatase > 3 times normal upper limit, total bilirubin > 2 times normal upper limit patients who are unwilling to anticipate.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: voriconazole treatment<br>induction treatment with Voriconazole 200mg bid (IV) + 5FC (100mg/kg/d) for 14 days, consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d | Drug: Voriconazole 200mg<br>* Induction treatment with voriconazole( 400mg/d)+5FC (100mg/kg/d) for 14 days;<br>* Other names: Voriconazole for Cryptococcus;|
| Active Comparator: amphotericin treatment (0.7-1.0mg/kg/d)<br>Induction treatment with amphotericin B 0.7-1.0mg/kg/d + 5FC (100mg/kg/d) for 14 days,consolidation treatment wiht fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d | Drug: Amphotericin B-deoxycholate (0.7-1.0mg/kg/d)<br>* Induction treatment with 0.7-1.0mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 14 days<br>* Other names: standard Amphotericin B-deoxycholate for Cryptococcus;|
| Experimental: amphotericin B treatment (0.4-0.5mg/kg/d)<br>Induction treatment with amphotericin B 0.4-0.5mg/kg/d + 5FC (100mg/kg/d) for 28 days, consolidation treatment with fluconazole 400mg/d for two months, then maintenance treatment with fluconazole 200mg/d | Drug: amphotericin B deoxycholate (0.4-0.5mg/kg/d)<br>* Induction treatment with 0.4-0.5mg/kg/d of Amphotericin B-deoxycholate +5FC(100mg/kg/d) for 28 days<br>* Other names: low dose and long course of Amphotericin B-deoxycholate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day Cryptococcal Meningitis (CM) related mortality | analysis of 90-day CM-related mortality of patients in three induction treatments | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early fungicidal rate in Cerebrospinal fluid (CSF) | Comparison of 2-week CSF early fungicidal activity in three induction treatments | 2 weeks | 
| creatinine elevation | TO observe the numbers of patients whose creatinine > 110 mmol/L during antifungal therapy | 0-90 days | 
| Hypokalemia | To observe the rate of hypokalemia in three groups during antifungal therapy | 0-90 days | 
| anemia | Comparison of the numbers of patients with hemoglobin <120g/L for male or <110g/L for female. | 0-90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Voriconazole;amphotericin ;cryptococcal meningitis