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Trial Outcomes & Findings for Tuberculosis and Human Immunodeficiency Virus (HIV) Immune Reconstitution Syndrome Trial (THIRST) (NCT NCT00851630)

NCT ID: NCT00851630

Last Updated: 2010-05-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

70 participants

Primary outcome timeframe

104 weeks

Results posted on

2010-05-04

Participant Flow

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.

Participant milestones

Participant milestones
Measure
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
Overall Study
STARTED
35
35
Overall Study
COMPLETED
33
33
Overall Study
NOT COMPLETED
2
2

Reasons for withdrawal

Reasons for withdrawal
Measure
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
Overall Study
Death
2
1
Overall Study
Clinical failure
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Early
n=35 Participants
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
n=35 Participants
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
n=70 Participants
Total of all reporting groups
Age, Categorical
<=18 years
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1.0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
34 Participants
n=5 Participants
35 Participants
n=7 Participants
69.0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0.0 Participants
n=5 Participants
Age Continuous
36.0 years
n=5 Participants
36.7 years
n=7 Participants
36.2 years
n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
17 Participants
n=7 Participants
29.0 Participants
n=5 Participants
Sex: Female, Male
Male
23 Participants
n=5 Participants
18 Participants
n=7 Participants
41.0 Participants
n=5 Participants
Region of Enrollment
Tanzania
35 participants
n=5 Participants
35 participants
n=7 Participants
70.0 participants
n=5 Participants

PRIMARY outcome

Timeframe: 104 weeks

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Early
n=35 Participants
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
n=35 Participants
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
Number of Serious Adverse Events (SAEs)
12 Events
7 Events

PRIMARY outcome

Timeframe: 104 weeks

Population: Intention to treat.

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.

Outcome measures

Outcome measures
Measure
Early
n=35 Participants
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
n=35 Participants
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
Tuberculosis-immune Reconstitution Inflammatory Syndrome Events
0 Events
0 Events

SECONDARY outcome

Timeframe: 104 Weeks

Population: Intention to Treat Analysis, missing = failure.

The number of subjects with plasma HIV RNA level \<400 copies/ml.

Outcome measures

Outcome measures
Measure
Early
n=35 Participants
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
n=35 Participants
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
Plasma HIV Ribonucleic Acid (RNA) Level < 400 Copies/ml
26 Participants
31 Participants

SECONDARY outcome

Timeframe: 104 Weeks

Population: Intent to Treat, missing = failure.

The number of subjects with plasma HIV RNA level \<50 copies/ml.

Outcome measures

Outcome measures
Measure
Early
n=35 Participants
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
n=35 Participants
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
HIV RNA Level < 50 Copies/ml
23 Participants
26 Participants

Adverse Events

Early

Serious events: 12 serious events
Other events: 0 other events
Deaths: 0 deaths

Delayed

Serious events: 7 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Early
n=35 participants at risk
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
n=35 participants at risk
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
Gastrointestinal disorders
Acute intestinal obstruction
2.9%
1/35 • Number of events 1
0.00%
0/35
Immune system disorders
Allergic reaction to suphalene-pyrimethamine
0.00%
0/35
2.9%
1/35 • Number of events 1
Infections and infestations
Amebiasis
2.9%
1/35 • Number of events 1
0.00%
0/35
Blood and lymphatic system disorders
Anemia
5.7%
2/35 • Number of events 2
0.00%
0/35
Infections and infestations
Cryptococcal meningitis
2.9%
1/35 • Number of events 1
0.00%
0/35
Skin and subcutaneous tissue disorders
Disseminated kaposi's sarcoma
0.00%
0/35
2.9%
1/35 • Number of events 1
Gastrointestinal disorders
Esophageal variceal bleeding
0.00%
0/35
2.9%
1/35 • Number of events 1
Nervous system disorders
Head trauma, grand mal seizure
0.00%
0/35
2.9%
1/35 • Number of events 1
Infections and infestations
Malaria
5.7%
2/35 • Number of events 2
2.9%
1/35 • Number of events 1
Infections and infestations
Mycobacteremia with M. sherrisii
0.00%
0/35
2.9%
1/35 • Number of events 1
Immune system disorders
Suspected abacavir hypersensitivity reaction
8.6%
3/35 • Number of events 3
2.9%
1/35 • Number of events 1
Infections and infestations
Syphilis
2.9%
1/35 • Number of events 1
0.00%
0/35
Respiratory, thoracic and mediastinal disorders
Tension pneumothorax
2.9%
1/35 • Number of events 1
0.00%
0/35

Other adverse events

Adverse event data not reported

Additional Information

Dr. Nathan Thielman

Duke University Medical Center

Phone: 919-6687174

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place