Cryptococcal Optimal ART Timing Trial (COAT)

This study has been completed.
Sponsor:
Collaborators:
Mbarara University of Science and Technology
Makerere University
University of Cape Town
Information provided by (Responsible Party):
David Boulware, University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT01075152
First received: February 23, 2010
Last updated: July 31, 2014
Last verified: July 2014
Results First Received: June 27, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Single Blind (Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Cryptococcal Meningitis
HIV Infections
AIDS
Interventions: Drug: efavirenz
Biological: nucleoside backbone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Earlier HIV Therapy HIV therapy initiated at 7-13 days after cryptococcal diagnosis
Deferred HIV Therapy HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/1 week)

Participant Flow:   Overall Study
    Earlier HIV Therapy     Deferred HIV Therapy  
STARTED     88 [1]   89 [1]
COMPLETED     87     89  
NOT COMPLETED     1     0  
Withdrawal by Subject                 1                 0  
[1] randomized



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
HIV-infected persons not previously receiving HIV therapy with first episode of cryptococcal meningitis diagnosed by CSF culture and/or CSF cryptococcal antigen testing.

Reporting Groups
  Description
Earlier HIV Therapy HIV therapy initiated at 7-13 days after cryptococcal meningitis diagnosis.
Deferred HIV Therapy HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week)
Total Total of all reporting groups

Baseline Measures
    Earlier HIV Therapy     Deferred HIV Therapy     Total  
Number of Participants  
[units: participants]
  88     89     177  
Age  
[units: years]
Median ( Inter-Quartile Range )
  35  
  ( 28 to 40 )  
  36  
  ( 30 to 40 )  
  35  
  ( 29 to 40 )  
Gender  
[units: participants]
     
Female     42     42     84  
Male     46     47     93  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     88     89     177  
White     0     0     0  
More than one race     0     0     0  
Unknown or Not Reported     0     0     0  
Region of Enrollment  
[units: participants]
     
Uganda     75     77     152  
South Africa     13     12     25  
CD4 Count, baseline  
[units: cells/mcL]
Median ( Inter-Quartile Range )
  19  
  ( 9 to 69 )  
  28  
  ( 11 to 76 )  
  23  
  ( 10 to 73 )  
CSF Quantitative Culture, baseline  
[units: log10 colony forming units/mL of CSF]
Median ( Inter-Quartile Range )
  5.3  
  ( 4.2 to 5.7 )  
  4.8  
  ( 3.8 to 5.5 )  
  5.1  
  ( 4.0 to 5.6 )  
CSF Cryptococcal Antigen titer, 1:xxxx [1]
[units: titers]
Median ( Inter-Quartile Range )
  8000  
  ( 2000 to 16000 )  
  4000  
  ( 1000 to 14400 )  
  6400  
  ( 2000 to 16000 )  
HIV-1 Viral Load  
[units: log10 copies/mL]
Median ( Inter-Quartile Range )
  5.5  
  ( 5.2 to 5.8 )  
  5.5  
  ( 5.3 to 5.8 )  
  5.5  
  ( 5.2 to 5.8 )  
[1] as performed by serial dilutions with lateral flow assay (LFA)



  Outcome Measures
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1.  Primary:   Mortality   [ Time Frame: 26 weeks from study entry ]

2.  Secondary:   Incidence of Immune Reconstitution Inflammatory Syndrome   [ Time Frame: 46 weeks ]

3.  Secondary:   Incidence of Cryptococcal-relapse   [ Time Frame: 46 weeks ]

4.  Secondary:   Safety of ART Initiation   [ Time Frame: 46 weeks ]

5.  Secondary:   46-week Survival   [ Time Frame: 46 weeks ]

6.  Secondary:   HIV-1 Viral Suppression   [ Time Frame: 26 weeks ]

7.  Secondary:   Antiretroviral Therapy Tolerability   [ Time Frame: 26 weeks ]

8.  Secondary:   Karnofsky Functional Status   [ Time Frame: 46 weeks ]

9.  Secondary:   Microbiologic Clearance   [ Time Frame: 4 weeks ]

10.  Other Pre-specified:   Percentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26   [ Time Frame: 26 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The differences in mortality in the two arms were of sufficient magnitude that trial enrollment was stopped early by the Data and Safety Monitoring Board. Historically, trials stopped early routinely over-estimate the magnitude of benefit or harm.


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Results Point of Contact:  
Name/Title: Dr. David R Boulware
Organization: University of Minnesota
phone: 6126249996
e-mail: boulw001@umn.edu


Publications of Results:
Other Publications:


Responsible Party: David Boulware, University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT01075152     History of Changes
Other Study ID Numbers: DAIDS-ES ID 10795, U01AI089244
Study First Received: February 23, 2010
Results First Received: June 27, 2014
Last Updated: July 31, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government
Uganda: National Council for Science and Technology
South Africa: Human Research Ethics Committee