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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)

Primary Purpose

Cryptococcal Meningitis, HIV

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fluconazole
Flucytosine
lumbar punctures
Sponsored by
ANRS, Emerging Infectious Diseases
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryptococcal Meningitis focused on measuring Cryptococcal meningitis, HIV Infections, Oral treatment, High dose of fluconazole, Flucytosine, Burundi, Ivory Coast

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • CHU Kamenge
  • Hôpital Prince Régent Charles
  • Hôpital général
  • Hôpital général
  • Hôpital général
  • Service de Maladies Infectieuses & Tropicales - Hôpital Triechville
  • Service de Neurologie - Hôpital Cocody

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

oral treatment

Arm Description

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)

Outcomes

Primary Outcome Measures

Mortality rate

Secondary Outcome Measures

Mortality rate
Percentage of patients with negative cerebrospinal fluid (CSF) cultures
Number of relapses of cryptococcal throughout the monitoring period
Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period
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
Cerebrospinal fluid pressure evolution
Percentage of patients with undetectable viral load
CD4 count
Concentration of flucytosine in cerebrospinal fluid
Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)
on urines, plasma, CSF and whole blood fingerstick
CSF total volume discharged
Number of lumbar punctures performed
Concentration of fluconazole in plasma
Concentration of fluconazole in cerebrospinal fluid
Concentration of flucytosine in plasma
MICs of fluconazole
MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse

Full Information

First Posted
October 19, 2012
Last Updated
July 11, 2016
Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
CHU Kamenge, BURUNDI, Hospital Avicenne, Institut Pasteur, Hôpital Necker-Enfants Malades, Institut de Médecine et Epidémiologie Appliquée (IMEA), Hôpital de Treichville, Hôpital Cocody
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1. Study Identification

Unique Protocol Identification Number
NCT01715922
Brief Title
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
Acronym
Flucocrypto
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Unknown status
Study Start Date
May 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ANRS, Emerging Infectious Diseases
Collaborators
CHU Kamenge, BURUNDI, Hospital Avicenne, Institut Pasteur, Hôpital Necker-Enfants Malades, Institut de Médecine et Epidémiologie Appliquée (IMEA), Hôpital de Treichville, Hôpital Cocody

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of the trial is to demonstrate that in a sub-Saharan African setting, 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryptococcal Meningitis, HIV
Keywords
Cryptococcal meningitis, HIV Infections, Oral treatment, High dose of fluconazole, Flucytosine, Burundi, Ivory Coast

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
oral treatment
Arm Type
Other
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Fluconazole
Intervention Description
Induction treatment for 2 weeks: Fluconazole (1600mg/j) Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
Intervention Type
Drug
Intervention Name(s)
Flucytosine
Intervention Description
Flucytosine (100 mg/kg/j) for 2 weeks
Intervention Type
Procedure
Intervention Name(s)
lumbar punctures
Intervention Description
lumbar punctures to control intracranial pressure
Primary Outcome Measure Information:
Title
Mortality rate
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Mortality rate
Time Frame
14 days and 24 weeks
Title
Percentage of patients with negative cerebrospinal fluid (CSF) cultures
Time Frame
14 days and 10 weeks
Title
Number of relapses of cryptococcal throughout the monitoring period
Time Frame
up to 24 weeks
Title
Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period
Description
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.
Time Frame
up to 24 weeks
Title
Number and severity of adverse events
Time Frame
up to 24 weeks
Title
Cerebrospinal fluid pressure evolution
Time Frame
up to 24 weeks
Title
Percentage of patients with undetectable viral load
Time Frame
24 weeks
Title
CD4 count
Time Frame
24 weeks
Title
Concentration of flucytosine in cerebrospinal fluid
Time Frame
28 days or 10 weeks
Title
Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)
Description
on urines, plasma, CSF and whole blood fingerstick
Time Frame
at study entry
Title
CSF total volume discharged
Time Frame
up to 24 weeks
Title
Number of lumbar punctures performed
Time Frame
up to 24 weeks
Title
Concentration of fluconazole in plasma
Time Frame
28 days or 10 weeks
Title
Concentration of fluconazole in cerebrospinal fluid
Time Frame
28 days or 10 weeks
Title
Concentration of flucytosine in plasma
Time Frame
28 days or 10 weeks
Title
MICs of fluconazole
Description
MICs of fluconazole for cryptococcus strains, if CSF cultures ar positive at 28 days or 10 weeks or in case of relapse
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Bouchaud, PhD
Organizational Affiliation
Hopital Avicenne, Service des maladies infectieuses, Paris, france
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Théodore Niyangobo, PhD
Organizational Affiliation
CHU Kamenge, Bujumbura, Burundi
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Amélie Chabrol, MD
Organizational Affiliation
Hopital Avicenne, Service des maladies infectieuses, Paris, france
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Kakou AKA, Professor
Organizational Affiliation
CHU Triechville
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Kamenge
City
Bujumbura
Country
Burundi
Facility Name
Hôpital Prince Régent Charles
City
Bujumbura
Country
Burundi
Facility Name
Hôpital général
City
Bururi
Country
Burundi
Facility Name
Hôpital général
City
Kayanza
Country
Burundi
Facility Name
Hôpital général
City
Muyinga
Country
Burundi
Facility Name
Service de Maladies Infectieuses & Tropicales - Hôpital Triechville
City
Abidjan
Country
Côte D'Ivoire
Facility Name
Service de Neurologie - Hôpital Cocody
City
Abidjan
Country
Côte D'Ivoire

12. IPD Sharing Statement

Links:
URL
http://www.anrs.fr
Description
Sponsor web page

Learn more about this trial

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

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