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 (Flucocrypto)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
CHU Kamenge, BURUNDI
Hospital Avicenne
Institut Pasteur
Hôpital Necker-Enfants Malades
Institut de Médecine et Epidémiologie Appliquée (IMEA)
Hôpital de Treichville
Hôpital Cocody
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01715922
First received: October 19, 2012
Last updated: May 7, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Cryptococcal Meningitis
HIV
Drug: Fluconazole
Drug: Flucytosine
Procedure: lumbar punctures
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Mortality rate [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mortality rate [ Time Frame: 14 days and 24 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients with negative cerebrospinal fluid (CSF) cultures [ Time Frame: 14 days and 10 weeks ] [ Designated as safety issue: No ]
  • Number of relapses of cryptococcal throughout the monitoring period [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
  • Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    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 and severity of adverse events [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Cerebrospinal fluid pressure evolution [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with undetectable viral load [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • CD4 count [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Concentration of flucytosine in cerebrospinal fluid [ Time Frame: 28 days or 10 weeks ] [ Designated as safety issue: No ]
  • Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay) [ Time Frame: at study entry ] [ Designated as safety issue: No ]
    on urines, plasma, CSF and whole blood fingerstick

  • CSF total volume discharged [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
  • Number of lumbar punctures performed [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
  • Concentration of fluconazole in plasma [ Time Frame: 28 days or 10 weeks ] [ Designated as safety issue: No ]
  • Concentration of fluconazole in cerebrospinal fluid [ Time Frame: 28 days or 10 weeks ] [ Designated as safety issue: No ]
  • Concentration of flucytosine in plasma [ Time Frame: 28 days or 10 weeks ] [ Designated as safety issue: No ]
  • MICs of fluconazole [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse


Estimated Enrollment: 61
Study Start Date: May 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
oral treatment

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01715922

Locations
Burundi
CHU Kamenge
Bujumbura, Burundi
Hôpital Prince Régent Charles
Bujumbura, Burundi
Hôpital général
Bururi, Burundi
Hôpital général
Kayanza, Burundi
Hôpital général
Muyinga, Burundi
Côte D'Ivoire
Service de Maladies Infectieuses & Tropicales - Hôpital Triechville
Abidjan, Côte D'Ivoire
Service de Neurologie - Hôpital Cocody
Abidjan, Côte D'Ivoire
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
CHU Kamenge, BURUNDI
Hospital Avicenne
Institut Pasteur
Hôpital Necker-Enfants Malades
Institut de Médecine et Epidémiologie Appliquée (IMEA)
Hôpital de Treichville
Hôpital Cocody
Investigators
Study Chair: Olivier Bouchaud, PhD Hopital Avicenne, Service des maladies infectieuses, Paris, france
Study Chair: Théodore Niyangobo, PhD CHU Kamenge, Bujumbura, Burundi
Principal Investigator: Amélie Chabrol, MD Hopital Avicenne, Service des maladies infectieuses, Paris, france
Principal Investigator: Kakou AKA, Professor CHU Triechville
  More Information

Additional Information:
No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01715922     History of Changes
Other Study ID Numbers: ANRS 12257 Flucocrypto
Study First Received: October 19, 2012
Last Updated: May 7, 2014
Health Authority: Burundi: Ministry of Health

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
Cryptococcal meningitis
HIV Infections
Oral treatment
High dose of fluconazole
Flucytosine
Burundi
Ivory Coast

Additional relevant MeSH terms:
Meningitis
Meningitis, Cryptococcal
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Fluconazole
Flucytosine
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites

ClinicalTrials.gov processed this record on August 20, 2014