Clinical trial NCT01715922: Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Sub-saharan Africa
Official title: Prospective Pilot Study to Evaluate a Standardized Management of Cryptococcal Meningitis in Patients Infected With HIV in Sub-Saharan Africa Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Complemented by Repeat Lumbar Punctures
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Cryptococcal Meningitis
HIV
Keywords: Cryptococcal meningitis
HIV Infections
Oral treatment
High dose of fluconazole
Flucytosine
Burundi
Ivory Coast
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: CHU Kamenge, BURUNDI
name: Hospital Avicenne
name: Institut Pasteur
name: Hôpital Necker-Enfants Malades
name: Institut de Médecine et Epidémiologie Appliquée (IMEA)
name: Hôpital de Treichville
name: Hôpital Cocody
First posted: 2012-10-29
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mortality rate
timeFrame: 10 weeks
Secondary outcomes:
measure: Mortality rate
timeFrame: 14 days and 24 weeks
measure: Percentage of patients with negative cerebrospinal fluid (CSF) cultures
timeFrame: 14 days and 10 weeks
measure: Number of relapses of cryptococcal throughout the monitoring period
timeFrame: up to 24 weeks
measure: Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period
timeFrame: up to 24 weeks
measure: Number and severity of adverse events
timeFrame: up to 24 weeks
measure: Cerebrospinal fluid pressure evolution
timeFrame: up to 24 weeks
measure: Percentage of patients with undetectable viral load
timeFrame: 24 weeks
measure: CD4 count
timeFrame: 24 weeks
measure: Concentration of flucytosine in cerebrospinal fluid
timeFrame: 28 days or 10 weeks
measure: Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)
timeFrame: at study entry
measure: CSF total volume discharged
timeFrame: up to 24 weeks
measure: Number of lumbar punctures performed
timeFrame: up to 24 weeks
measure: Concentration of fluconazole in plasma
timeFrame: 28 days or 10 weeks
measure: Concentration of fluconazole in cerebrospinal fluid
timeFrame: 28 days or 10 weeks
measure: Concentration of flucytosine in plasma
timeFrame: 28 days or 10 weeks
measure: MICs of fluconazole
timeFrame: 28 days
Other outcomes:
Locations:
city: Bujumbura
country: Burundi
facility: CHU Kamenge
city: Bujumbura
country: Burundi
facility: Hôpital Prince Régent Charles
city: Bururi
country: Burundi
facility: Hôpital général
city: Kayanza
country: Burundi
facility: Hôpital général
city: Muyinga
country: Burundi
facility: Hôpital général
city: Abidjan
country: Côte D'Ivoire
facility: Service de Maladies Infectieuses & Tropicales - Hôpital Triechville
city: Abidjan
country: Côte D'Ivoire
facility: Service de Neurologie - Hôpital Cocody
Study officials:
affiliation: Hopital Avicenne, Service des maladies infectieuses, Paris, france
name: Olivier Bouchaud, PhD
role: STUDY_CHAIR
affiliation: CHU Kamenge, Bujumbura, Burundi
name: Théodore Niyangobo, PhD
role: STUDY_CHAIR
affiliation: Hopital Avicenne, Service des maladies infectieuses, Paris, france
name: Amélie Chabrol, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Triechville
name: Kakou AKA, Professor
role: PRINCIPAL_INVESTIGATOR
References: