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

October 19, 2012
May 7, 2014
May 2012
August 2015   (final data collection date for primary outcome measure)
Mortality rate [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
mortality rates [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01715922 on ClinicalTrials.gov Archive Site
  • 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
  • mortality rates [ Time Frame: 14 days and 24 weeks ] [ Designated as safety issue: Yes ]
  • Percentage of patients with culture negative cerebrospinal fluid (CSF) [ Time Frame: 14 days and 10 weeks ] [ Designated as safety issue: No ]
  • Number of relapse 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 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: 24weeks ] [ 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
  • Severity of adverse events [ Time Frame: up to 24 weeks ] [ Designated as safety issue: Yes ]
  • 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 ]
Not Provided
Not Provided
 
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
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

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.

Not Provided
Interventional
Phase 2
Phase 3
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cryptococcal Meningitis
  • HIV
  • 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
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)

Interventions:
  • Drug: Fluconazole
  • Drug: Flucytosine
  • Procedure: lumbar punctures
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
61
December 2015
August 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Burundi,   Côte D'Ivoire
 
NCT01715922
ANRS 12257 Flucocrypto
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
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
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
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP