Cryptococcal Meningitis, HIV
Conditions
Keywords
Cryptococcal meningitis, HIV Infections, Oral treatment, High dose of fluconazole, Flucytosine, Burundi, Ivory Coast
Brief summary
The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association of: 1. Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy 2. lumbar punctures to control intracranial pressure can decrease mortality rate below 35% at 10 weeks. This is a non-randomized open label pilot study, with standardized management of cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients will be enrolled.
Interventions
DRUGFluconazole
Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
DRUGFlucytosine
Flucytosine (100 mg/kg/j) for 2 weeks
PROCEDURElumbar punctures
lumbar punctures to control intracranial pressure
Sponsors
CHU Kamenge, BURUNDI
Hospital Avicenne
Institut Pasteur
Hôpital Necker-Enfants Malades
Institut de Médecine et Epidémiologie Appliquée (IMEA)
Hôpital de Treichville
Hôpital Cocody
ANRS, Emerging Infectious Diseases
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* \> 18 years * HIV Infection * First episode of cryptococcal meningitis on basis CSF India ink and/or CSF cryptococcal antigen. * Glasgow \> 9 after lumbar punctures * Absence of peripheral focal deficit in the limbs * informed consent signed
Exclusion criteria
* Hemoglobin \<7.5 g / dl; * neutrophils count \<500/mm3; * Platelets count \<50 000/mm3; * transaminases \> 5 times upper limit of normal; * Troubles with severe mental alertness Glasgow \<9 after the initial lumbar puncture; * focal neurological deficit in the limbs; * Pregnancy or lactation on going; * Ongoing systemic antifungal treatment; * History of cryptococcal meningitis; * Ongoing rifampicin and ritonavir treatment; * Subject participating in another study with a risk of mutual interference on the interpretation of results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mortality rate | 10 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of fluconazole in plasma | 28 days or 10 weeks | — |
| Concentration of fluconazole in cerebrospinal fluid | 28 days or 10 weeks | — |
| Concentration of flucytosine in plasma | 28 days or 10 weeks | — |
| Mortality rate | 14 days and 24 weeks | — |
| Percentage of patients with negative cerebrospinal fluid (CSF) cultures | 14 days and 10 weeks | — |
| Number of relapses of cryptococcal throughout the monitoring period | up to 24 weeks | — |
| Number of Immune Reconstitution Inflammatory Syndrome (IRIS) throughout the monitoring period | up to 24 weeks | The IRIS diagnosis criteria will be those given in: Bicanic T, et al. Immune Reconstitution Inflammatory Syndrome in HIV-associated cryptococcal meningitis: a prospective study, J Acquir Immune Defic Syndr 2009; 51:130-134. |
| Number of lumbar punctures performed | up to 24 weeks | — |
| Cerebrospinal fluid pressure evolution | up to 24 weeks | — |
| Percentage of patients with undetectable viral load | 24 weeks | — |
| CD4 count | 24 weeks | — |
| Concentration of flucytosine in cerebrospinal fluid | 28 days or 10 weeks | — |
| Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay) | at study entry | on urines, plasma, CSF and whole blood fingerstick |
| CSF total volume discharged | up to 24 weeks | — |
| MICs of fluconazole | 28 days | MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse |
| Number and severity of adverse events | up to 24 weeks | — |
Countries
Burundi, Côte d’Ivoire
Outcome results
None listed