Cryptococcal Optimal ART Timing Trial (COAT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01075152
Recruitment Status : Completed
First Posted : February 24, 2010
Results First Posted : August 20, 2014
Last Update Posted : August 26, 2015
Mbarara University of Science and Technology
Makerere University
National Institute of Allergy and Infectious Diseases (NIAID)
University of Cape Town
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Conditions: Cryptococcal Meningitis
HIV Infections
Interventions: Drug: efavirenz
Biological: nucleoside

  Participant Flow

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
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 
Withdrawal by Subject                1                0 
[1] randomized

  Baseline Characteristics

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
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 
Overall Participants Analyzed 
[Units: Participants]
 88   89   177 
[Units: Years]
Median (Inter-Quartile Range)
 (28 to 40) 
 (30 to 40) 
 (29 to 40) 
[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)
 (9 to 69) 
 (11 to 76) 
 (10 to 73) 
CSF Quantitative Culture, baseline 
[Units: Log10 colony forming units/mL of CSF]
Median (Inter-Quartile Range)
 (4.2 to 5.7) 
 (3.8 to 5.5) 
 (4.0 to 5.6) 
CSF Cryptococcal Antigen titer, 1:xxxx [1] 
[Units: Titers]
Median (Inter-Quartile Range)
 (2000 to 16000) 
 (1000 to 14400) 
 (2000 to 16000) 
[1] as performed by serial dilutions with lateral flow assay (LFA)
HIV-1 Viral Load 
[Units: Log10 copies/mL]
Median (Inter-Quartile Range)
 (5.2 to 5.8) 
 (5.3 to 5.8) 
 (5.2 to 5.8) 

  Outcome Measures

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

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

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

Publications of Results:
Other Publications:

Responsible Party: University of Minnesota - Clinical and Translational Science Institute Identifier: NCT01075152     History of Changes
Other Study ID Numbers: DAIDS-ES ID 10795
U01AI089244 ( U.S. NIH Grant/Contract )
First Submitted: February 23, 2010
First Posted: February 24, 2010
Results First Submitted: June 27, 2014
Results First Posted: August 20, 2014
Last Update Posted: August 26, 2015