Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST)

This study has been completed.
Sponsor:
Collaborators:
Kilimanjaro Christian Medical Centre, Tanzania
Kibongoto National Tuberculosis Hospital, Tanzania
GlaxoSmithKline
Information provided by:
Duke University
ClinicalTrials.gov Identifier:
NCT00851630
First received: February 25, 2009
Last updated: May 2, 2010
Last verified: May 2010
Results First Received: March 15, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: HIV
Tuberculosis
Intervention: Drug: Fixed dose combination zidovudine/lamivudine/abacavir

  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
Enrollment began in June 2004 and was completed in September 2005. Patients were enrolled at one of two hospitals in the Kilimanjaro Region of Tanzania.

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
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy

Participant Flow:   Overall Study
    Early     Delayed  
STARTED     35     35  
COMPLETED     33     33  
NOT COMPLETED     2     2  
Death                 2                 1  
Clinical failure                 0                 1  



  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.
No text entered.

Reporting Groups
  Description
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy
Total Total of all reporting groups

Baseline Measures
    Early     Delayed     Total  
Number of Participants  
[units: participants]
  35     35     70  
Age  
[units: participants]
     
<=18 years     1     0     1  
Between 18 and 65 years     34     35     69  
>=65 years     0     0     0  
Age  
[units: years]
Median ( Inter-Quartile Range )
  36.0  
  ( 32.4 to 43.6 )  
  36.7  
  ( 32.4 to 44.3 )  
  36.2  
  ( 32.4 to 43.6 )  
Gender  
[units: participants]
     
Female     12     17     29  
Male     23     18     41  
Region of Enrollment  
[units: participants]
     
Tanzania     35     35     70  



  Outcome Measures
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1.  Primary:   Number of Serious Adverse Events (SAEs)   [ Time Frame: 104 weeks ]

Measure Type Primary
Measure Title Number of Serious Adverse Events (SAEs)
Measure Description Feasibility and safety of fixed dose combination zidovudine/lamivudine/abacavir in HIV-infected subjects with tuberculosis in a resource-limited setting as assessed by the number of serious adverse events. Serious adverse events included any untoward medical occurrence that resulted in death, was considered life-threatening, required inpatient hospitalization or prolongation of existing hospitalization beyond what was required in the study, or resulted in persistent or resulted in significant disability/incapacity.
Time Frame 104 weeks  
Safety Issue Yes  

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.
Intention to treat.

Reporting Groups
  Description
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy

Measured Values
    Early     Delayed  
Number of Participants Analyzed  
[units: participants]
  35     35  
Number of Serious Adverse Events (SAEs)  
[units: Events]
  12     7  

No statistical analysis provided for Number of Serious Adverse Events (SAEs)



2.  Primary:   Tuberculosis-immune Reconstitution Inflammatory Syndrome Events   [ Time Frame: 104 weeks ]

Measure Type Primary
Measure Title Tuberculosis-immune Reconstitution Inflammatory Syndrome Events
Measure Description Tuberculosis-immune reconstitution inflammatory syndrome was defined by the protocol as: a) new persistent fevers (temperature >101.5 degrees Fahrenheit) developing after the initiation of antiretroviral therapy, and not believed to be associated with antiretroviral therapy and without an identifiable source, b) marked worsening or emergence of intrathoracic lymphadenopathy, pulmonary infiltrates or pleural effusions on radiologic examination, or c) worsening or emergence of lymphadenopathy on serial examinations or worsening of other tuberculous lesions.
Time Frame 104 weeks  
Safety Issue Yes  

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.
Intention to treat.

Reporting Groups
  Description
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy

Measured Values
    Early     Delayed  
Number of Participants Analyzed  
[units: participants]
  35     35  
Tuberculosis-immune Reconstitution Inflammatory Syndrome Events  
[units: Events]
  0     0  

No statistical analysis provided for Tuberculosis-immune Reconstitution Inflammatory Syndrome Events



3.  Secondary:   Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml   [ Time Frame: 104 Weeks ]

Measure Type Secondary
Measure Title Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml
Measure Description The number of subjects with plasma HIV RNA level <400 copies/ml.
Time Frame 104 Weeks  
Safety Issue No  

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.
Intention to Treat Analysis, missing = failure.

Reporting Groups
  Description
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy

Measured Values
    Early     Delayed  
Number of Participants Analyzed  
[units: participants]
  35     35  
Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml  
[units: Participants]
  26     31  

No statistical analysis provided for Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml



4.  Secondary:   HIV RNA Level < 50 Copies/ml   [ Time Frame: 104 Weeks ]

Measure Type Secondary
Measure Title HIV RNA Level < 50 Copies/ml
Measure Description The number of subjects with plasma HIV RNA level <50 copies/ml.
Time Frame 104 Weeks  
Safety Issue No  

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.
Intent to Treat, missing = failure.

Reporting Groups
  Description
Early Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 2 weeks after commencing antituberculous therapy
Delayed Initiation of fixed dose combination zidovudine (300 mg)/lamivudine (150 mg)/abacavir (300 mg) administered orally twice daily, beginning 8 weeks after commencing antituberculous therapy

Measured Values
    Early     Delayed  
Number of Participants Analyzed  
[units: participants]
  35     35  
HIV RNA Level < 50 Copies/ml  
[units: Participants]
  23     26  

No statistical analysis provided for HIV RNA Level < 50 Copies/ml




  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
No text entered.


  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. Nathan Thielman
Organization: Duke University Medical Center
phone: 919-6687174
e-mail: n.thielman@duke.edu


Publications of Results:

Responsible Party: Nathan Thielman, MD, MPH, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00851630     History of Changes
Other Study ID Numbers: Pro00013131
Study First Received: February 25, 2009
Results First Received: March 15, 2009
Last Updated: May 2, 2010
Health Authority: United States: Institutional Review Board
Tanzania: National Institute for Medical Research
Tanzania: Food & Drug Administration