Trial Outcomes & Findings for Study of Limited Versus Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana (NCT NCT00164281)
NCT ID: NCT00164281
Last Updated: 2026-05-27
Results Overview
Incident tuberculosis during follow-up. Tuberculosis cases were categorized as: Definite: ≥1 positive culture for M. tuberculosis or ≥2 sputum smears positive for acid-fast bacilli; Probable: 1 sputum smear or biopsy specimen positive for acid-fast bacilli; Possible: clinical diagnosis with negative or unavailable smear/culture results. Outcome data include definite, probable, and possible tuberculosis cases combined, consistent with the published analysis.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1995 participants
Primary outcome timeframe
During follow-up (36 months)
Results posted on
2026-05-27
Participant Flow
The planned sample size was 2000 participants; however, 1995 participants were ultimately enrolled and randomized.
Participant milestones
| Measure |
Continuous Isoniazid Arm
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
|---|---|---|
|
Overall Study
STARTED
|
1006
|
989
|
|
Overall Study
COMPLETED
|
851
|
827
|
|
Overall Study
NOT COMPLETED
|
155
|
162
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study of Limited Versus Continuous Isoniazid Tuberculosis Preventive Therapy in HIV-infected Persons in Botswana
Baseline characteristics by cohort
| Measure |
Continuous Isoniazid Arm
n=1006 Participants
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid) for an additional 30 months.
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
n=989 Participants
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
Total
n=1995 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1006 Participants
n=51 Participants
|
989 Participants
n=14 Participants
|
1995 Participants
n=65 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Sex: Female, Male
Female
|
715 Participants
n=51 Participants
|
721 Participants
n=14 Participants
|
1436 Participants
n=65 Participants
|
|
Sex: Female, Male
Male
|
291 Participants
n=51 Participants
|
268 Participants
n=14 Participants
|
559 Participants
n=65 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1006 Participants
n=51 Participants
|
989 Participants
n=14 Participants
|
1995 Participants
n=65 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=51 Participants
|
0 Participants
n=14 Participants
|
0 Participants
n=65 Participants
|
|
Region of Enrollment
Botswana
|
1006 Participants
n=51 Participants
|
989 Participants
n=14 Participants
|
1995 Participants
n=65 Participants
|
PRIMARY outcome
Timeframe: During follow-up (36 months)Incident tuberculosis during follow-up. Tuberculosis cases were categorized as: Definite: ≥1 positive culture for M. tuberculosis or ≥2 sputum smears positive for acid-fast bacilli; Probable: 1 sputum smear or biopsy specimen positive for acid-fast bacilli; Possible: clinical diagnosis with negative or unavailable smear/culture results. Outcome data include definite, probable, and possible tuberculosis cases combined, consistent with the published analysis.
Outcome measures
| Measure |
Continuous Isoniazid Arm
n=1006 Participants
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
n=989 Participants
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
|---|---|---|
|
Number of Participants With Incident Tuberculosis
|
20 Participants
|
34 Participants
|
SECONDARY outcome
Timeframe: During follow-up (36 months)Population: All randomized participants were included in the mortality analysis (Continuous isoniazid arm: N=1006; placebo arm: N=989).
All-cause mortality during the 36-month follow-up period.
Outcome measures
| Measure |
Continuous Isoniazid Arm
n=1006 Participants
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
n=989 Participants
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
|---|---|---|
|
Number of Participants Who Died
|
39 Participants
|
38 Participants
|
SECONDARY outcome
Timeframe: During follow-up (36 months)Population: All randomized participants were included in the composite tuberculosis and death analysis.
Composite of incident tuberculosis and all deaths during the 36-month follow-up period. The paper presents this as "Tuberculosis and all deaths."
Outcome measures
| Measure |
Continuous Isoniazid Arm
n=1006 Participants
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
n=989 Participants
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
|---|---|---|
|
Tuberculosis and Death Composite Outcome
|
59 Participants
|
72 Participants
|
Adverse Events
Continuous Isoniazid Arm
Serious events: 9 serious events
Other events: 0 other events
Deaths: 39 deaths
Limited (Placebo) Isoniazid Arm
Serious events: 6 serious events
Other events: 0 other events
Deaths: 38 deaths
Serious adverse events
| Measure |
Continuous Isoniazid Arm
n=1006 participants at risk
The treatment (experimental arm or continuous arm) will receive 6 months of open label isoniazid before beginning coded medication (isoniazid).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 36 months.
|
Limited (Placebo) Isoniazid Arm
n=989 participants at risk
The placebo arm will receive 6 months of open label isoniazid before beginning placebo (as a coded medication).
Isoniazid: Daily 300 mg isoniazid supplemented with 25 mg pyridoxine for 6 months.
|
|---|---|---|
|
Hepatobiliary disorders
Hepatitis
|
0.89%
9/1006 • Number of events 9 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
0.61%
6/989 • Number of events 989 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.10%
1/1006 • Number of events 1 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
0.10%
1/989 • Number of events 1 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
|
Nervous system disorders
Seizure
|
0.10%
1/1006 • Number of events 1 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
0.00%
0/989 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
|
Nervous system disorders
Peripheral Neuropathy
|
0.10%
1/1006 • Number of events 1 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
0.00%
0/989 • From initiation of study medication through 36 months of follow-up
Serious and non-serious adverse events were monitored throughout treatment and follow-up and classified by severity and relationship to study medication.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place