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

NCT01715922 | Unknown Phase 2 DMC

• 1 other identifier: ANRS 12257 Flucocrypto
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 7

Brief Summary

The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association of:

1. 1.Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy
2. 2.lumbar punctures to control intracranial pressure

Conditions

Cryptococcal Meningitis; HIV

Keywords

Cryptococcal meningitis; HIV Infections; Oral treatment; High dose of fluconazole; Flucytosine; Burundi; Ivory Coast

Outcome Measures

Primary Outcomes (1)

• Mortality rate

  10 weeks

Secondary Outcomes (16)

• 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

• Number and severity of adverse events

  up to 24 weeks

Study Arms (1)

oral treatment

OTHER

Drug: Fluconazole and flucytosine Induction treatment for 2 weeks: Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)

Drug: Fluconazole; Drug: Flucytosine; Procedure: lumbar punctures

Interventions

Fluconazole DRUG

Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)

oral treatment

Flucytosine DRUG

Flucytosine (100 mg/kg/j) for 2 weeks

oral treatment

lumbar punctures PROCEDURE

lumbar punctures to control intracranial pressure

oral treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \> 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• CHU Kamenge, BURUNDI: collaborator
• Hospital Avicenne: collaborator
• Institut Pasteur: collaborator
• Hôpital Necker-Enfants Malades: collaborator
• Institut de Médecine et Epidémiologie Appliquée (IMEA): collaborator
• Hôpital de Treichville: collaborator
• Hôpital Cocody: collaborator

Study Sites (7)

CHU Kamenge

Bujumbura, Burundi

Location

Hôpital Prince Régent Charles

Bujumbura, Burundi

Location

Hôpital général

Bururi, Burundi

Location

Hôpital général

Kayanza, Burundi

Location

Hôpital général

Muyinga, Burundi

Location

Service de Maladies Infectieuses & Tropicales - Hôpital Triechville

Abidjan, Côte d’Ivoire

Location

Service de Neurologie - Hôpital Cocody

Abidjan, Côte d’Ivoire

Location

Related Links

• Sponsor web page

MeSH Terms

Conditions

Meningitis, Cryptococcal; HIV Infections

Interventions

Fluconazole; Flucytosine; Spinal Puncture

Condition Hierarchy (Ancestors)

Meningitis, Fungal; Central Nervous System Fungal Infections; Mycoses; Bacterial Infections and Mycoses; Infections; Cryptococcosis; Central Nervous System Infections; Central Nervous System Diseases; Nervous System Diseases; Meningitis; Neuroinflammatory Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cytosine; Pyrimidinones; Pyrimidines; Biopsy; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Olivier Bouchaud, PhD

  Hopital Avicenne, Service des maladies infectieuses, Paris, france

  STUDY CHAIR

• Théodore Niyangobo, PhD

  CHU Kamenge, Bujumbura, Burundi

  STUDY CHAIR

• Amélie Chabrol, MD

  Hopital Avicenne, Service des maladies infectieuses, Paris, france

  PRINCIPAL INVESTIGATOR

• Kakou AKA, Professor

  CHU Triechville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2012
• First Posted: October 29, 2012
• Study Start: May 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2016
• Last Updated: July 12, 2016

Record last verified: 2016-07

Locations

BU (5); CÔ (2)