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Safety Study of Fluconazole in Combination With Flucytosine for the Treatment of Early Cryptococcal Infection (SToP-Crypto)

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ClinicalTrials.gov Identifier: NCT01562132
Recruitment Status : Terminated (Stopped in accordance with pre-specified stopping rules for poor recruitment.)
First Posted : March 23, 2012
Results First Posted : August 31, 2015
Last Update Posted : August 31, 2015
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Kenya Medical Research Institute
Valeant Pharmaceuticals International, Inc.
University of Nairobi
Information provided by (Responsible Party):
Ana-Claire Meyer, Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cryptococcal Infection Disseminated
Interventions Drug: Flucytosine and fluconazole
Drug: Fluconazole
Enrollment 6
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 5FC Plus Fluconazole Fluconazole Alone
Hide Arm/Group Description

Combination therapy with oral fluconazole and flucytosine

Flucytosine and fluconazole: Flucytosine 100mg/kg/day in 4 divided doses orally for 14 days given in combination with fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Fluconazole monotherapy

Fluconazole: fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Period Title: Overall Study
Started 3 3
Completed 3 3
Not Completed 0 0
Arm/Group Title 5FC Plus Fluconazole Fluconazole Alone Total
Hide Arm/Group Description

Combination therapy with oral fluconazole and flucytosine

Flucytosine and fluconazole: Flucytosine 100mg/kg/day in 4 divided doses orally for 14 days given in combination with fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Fluconazole monotherapy

Fluconazole: fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Total of all reporting groups
Overall Number of Baseline Participants 3 3 6
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 6 participants
36
(28 to 49)
31
(26 to 58)
33.5
(26 to 58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 6 participants
Female
1
  33.3%
1
  33.3%
2
  33.3%
Male
2
  66.7%
2
  66.7%
4
  66.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Kenya Number Analyzed 3 participants 3 participants 6 participants
3 3 6
CD4+ T-cell Count  
Median (Full Range)
Unit of measure:  Cells/microliter
Number Analyzed 3 participants 3 participants 6 participants
22
(18 to 56)
13
(3 to 16)
17
(3 to 56)
1.Primary Outcome
Title Survival at 12 Weeks
Hide Description [Not Specified]
Time Frame 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 5FC Plus Fluconazole Fluconazole Alone
Hide Arm/Group Description:

Combination therapy with oral fluconazole and flucytosine

Flucytosine and fluconazole: Flucytosine 100mg/kg/day in 4 divided doses orally for 14 days given in combination with fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Fluconazole monotherapy

Fluconazole: fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Overall Number of Participants Analyzed 3 3
Measure Type: Number
Unit of Measure: participants
2 2
2.Secondary Outcome
Title Survival at 2 Weeks
Hide Description [Not Specified]
Time Frame 2 weeks
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Survival at 24 Weeks
Hide Description [Not Specified]
Time Frame 24 weeks
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Number of Individuals Who Develop Cryptococcal Meningitis
Hide Description

Clinical meningitis AND at least one of the following: cryptococcal antigen in the cerebrospinal fluid (CSF), cryptococcal organisms on India Ink stain, or fungal culture of CSF.

Clinical meningitis will be defined as:

  • fever>39.0°C, AND
  • severe headache, AND

At least one of the following:

  • meningismus,
  • photophobia,
  • new onset seizure,
  • focal neurological deficit localizable to the central nervous system
  • papilledema
  • confusion, delirium, or decreased level of consciousness.
Time Frame 24 weeks
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Number of Individuals Who Develop Immune Reconstitution Inflammatory Syndrome Due to Cryptococcus
Hide Description

Individuals who develop clinical meningitis without evidence of fungal, bacterial, or parasitic (e.g. malaria) organisms in the cerebrospinal fluid. Clinical meningitis will be defined as:

  • fever>39.0°C, AND
  • severe headache, AND
  • At least one of the following:
  • meningismus,
  • photophobia,
  • new onset seizure,
  • focal neurological deficit localizable to the central nervous system
  • papilledema
  • confusion, delirium, or decreased level of consciousness.
Time Frame 24 weeks
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Achieve Targeted Recruitment, Retention and Adherence Rates
Hide Description [Not Specified]
Time Frame 24 weeks
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Proportion of Individuals Requiring Treatment Discontinuation
Hide Description [Not Specified]
Time Frame 4 weeks
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Proportion of Individuals Requiring Dose Reduction
Hide Description [Not Specified]
Time Frame 24 weeks
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Number of Individuals With Treatment Related Adverse Events
Hide Description [Not Specified]
Time Frame 24 weeks
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Number of Individuals With Treatment Related Serious Adverse Events
Hide Description [Not Specified]
Time Frame 24 weeks
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Cryptococcal Meningitis-free Survival at 24 Weeks
Hide Description

Clinical meningitis AND at least one of the following: cryptococcal antigen in the cerebrospinal fluid (CSF), cryptococcal organisms on India Ink stain, or fungal culture of CSF.

Clinical meningitis will be defined as:

  • fever>39.0°C, AND
  • severe headache, AND

At least one of the following:

  • meningismus,
  • photophobia,
  • new onset seizure,
  • focal neurological deficit localizable to the central nervous system
  • papilledema
  • confusion, delirium, or decreased level of consciousness.
Time Frame 24 weeks
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 5FC Plus Fluconazole Fluconazole Alone
Hide Arm/Group Description

Combination therapy with oral fluconazole and flucytosine

Flucytosine and fluconazole: Flucytosine 100mg/kg/day in 4 divided doses orally for 14 days given in combination with fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

Fluconazole monotherapy

Fluconazole: fluconazole 1200mg orally once daily for 14 days, followed by 800mg orally once daily for 8 weeks, followed by 200mg orally once daily

All-Cause Mortality
5FC Plus Fluconazole Fluconazole Alone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
5FC Plus Fluconazole Fluconazole Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      0/3 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
5FC Plus Fluconazole Fluconazole Alone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      2/3 (66.67%)    
Blood and lymphatic system disorders     
Neutropenia  [1]  2/3 (66.67%)  2 1/3 (33.33%)  1
Gastrointestinal disorders     
Nausea  [1]  0/3 (0.00%)  0 1/3 (33.33%)  1
Vomiting  [2]  0/3 (0.00%)  0 1/3 (33.33%)  1
General disorders     
Unintentional Weight Loss  [2]  1/3 (33.33%)  1 0/3 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Grade 1
[2]
Grade 2
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Ana-Claire Meyer
Organization: Yale University
Phone: 203-737-8372
Responsible Party: Ana-Claire Meyer, Yale University
ClinicalTrials.gov Identifier: NCT01562132     History of Changes
Other Study ID Numbers: R21NS077858-01 ( U.S. NIH Grant/Contract )
R21NS077858-01 ( U.S. NIH Grant/Contract )
First Submitted: March 21, 2012
First Posted: March 23, 2012
Results First Submitted: July 31, 2015
Results First Posted: August 31, 2015
Last Update Posted: August 31, 2015