Text Size

Study Evaluating Efficiency and Tolerance of High-dose Fluconazole Associated With Flucytosine as Induction Therapy for Cryptococcal Meningitis Associated With HIV in Burundi

This study is currently recruiting participants.
Verified October 2012 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Collaborators:
CHU Kamenge, BURUNDI
Hospital Avicenne
Institut Pasteur
Hôpital Necker-Enfants Malades
Institut de Médecine et Epidémiologie Appliquée (IMEA)
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: October 25, 2012
Last verified: October 2012
History of Changes
  Purpose

The aim of the trial is to demonstrate that in a sub-Saharan African country, Burundi, 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
  3. early introduction of HAART (highly active antiretroviral therapy ) (at day 15 after anti-cryptococcoses initiation).

can decrease mortality rate below 40% at 10 weeks.

This is a non randomized open label pilot study, with standardized management of cryptococcoses meningitis and follow-up in Burundi. A total of 61 patients will be enrolled.


Condition Intervention Phase
Cryptococcal Meningitis
 Drug: Fluconazole
Drug: Flucytosine
Procedure: lumbar punctures
Drug: Anti-HIV Agents
 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 Burundi, Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Achieving Lumbar Punctures Meet the Guidelines and an Introduction 15 Days of Antiretroviral Therapy

Resource links provided by NLM:

U.S. FDA Resources

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 rates [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 61
Study Start Date: May 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (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 early introduction of HAART 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
Drug: Anti-HIV Agents
Early introduction of HAART

  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.
  • Patient naive to antiretroviral treatment. A history of PMTCT (prevention of mother-to-child transmission )is tolerated.
  • 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;
  • Antiretroviral therapy on going;
  • Antifungal systemically on going;
  • History of cryptococcal meningitis;
  • Subject participating in another study with a risk of mutual interference on the interpretation of results.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01715922

Contacts
Contact: Olivier Bouchaud, Ph.D 0033 1 48 95 54 21 olivier.bouchaud@avc.aphp.fr
Contact: Théodore Niyongabo, Ph.D thniyongabo@yahoo.fr

Locations
Burundi
CHU Kamenge Recruiting
Bujumbura, Burundi
Contact: Sylvain SN Nzeyimana, Dr     79 953 588     dr_nzeyimana@yahoo.fr    
Hôpital Prince Régent Charles Recruiting
Bujumbura, Burundi
Contact: Eliane Musaninyange, Dr     77 731 561     museliane@yahoo.fr    
Hôpital général Recruiting
Bururi, Burundi
Contact: Audace Akimana, Dr     77 895 247     akiaudace@yahoo.fr    
Hôpital général Recruiting
Kayanza, Burundi
Contact: Adonis Ndayizeye, Dr     79 983 744     adonis-nday@yahoo.fr    
Hôpital général Recruiting
Muyinga, Burundi
Contact: Alexis Niyonzima, Dr     79 536 401     niyalexis@yahoo.fr    
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)
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
  More Information

Additional Information:
Sponsor web page  This link exits the ClinicalTrials.gov site

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: October 25, 2012
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

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
 Anti-HIV Agents
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Anti-Retroviral Agents
Antiviral Agents

ClinicalTrials.gov processed this record on March 10, 2013