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:
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
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
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Purpose
The aim of the trial is to demonstrate that in a sub-Saharan African country, Burundi, the association of:
- Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy
- lumbar punctures to control intracranial pressure
- 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:
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:
No publications provided
Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 10, 2013
Additional Information:
Sponsor web page 
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