Trial Outcomes & Findings for Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection (NCT NCT00023452)
NCT ID: NCT00023452
Last Updated: 2024-08-27
Results Overview
Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis \[MTB\]) and those \<18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, computed tomography \[CT\] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli \[AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach).
COMPLETED
PHASE3
8053 participants
Baseline up to Month 33
2024-08-27
Participant Flow
The protocol design allowed enrollment of participants identified as members of the same household or group setting (such as group homes, settings) in clusters. The same treatment regimen to which a first participant was randomized could be assigned to other cluster members. All other participants enrolled were randomized individually.
Participant milestones
| Measure |
9INH
Participants who were high-risk tuberculin skin test (TST) reactors (household and other close contacts of active tuberculosis \[TB\] cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on chest x-ray \[CXR\], human immunodeficiency virus \[HIV\] infected participants) self-administered oral isoniazid (INH) tablets (aged greater than or equal to \[≥12\] years of age received 5 milligrams per kilogram \[mg/kg\] and participants 2-11 years of age received 10-15 mg/kg) once daily for 9 months (240 to 270 total doses).
|
3RPT/INH
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV-infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral rifapentine (RPT) tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by Directly Observed Therapy (DOT), defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Overall Study
STARTED
|
3908
|
4145
|
|
Overall Study
Randomized
|
3190
|
3174
|
|
Overall Study
Enrolled as Part of a Cluster
|
718
|
971
|
|
Overall Study
Completed Treatment
|
2585
|
3273
|
|
Overall Study
Not Treated
|
149
|
105
|
|
Overall Study
Completed Study
|
3174
|
3475
|
|
Overall Study
COMPLETED
|
2585
|
3273
|
|
Overall Study
NOT COMPLETED
|
1323
|
872
|
Reasons for withdrawal
| Measure |
9INH
Participants who were high-risk tuberculin skin test (TST) reactors (household and other close contacts of active tuberculosis \[TB\] cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on chest x-ray \[CXR\], human immunodeficiency virus \[HIV\] infected participants) self-administered oral isoniazid (INH) tablets (aged greater than or equal to \[≥12\] years of age received 5 milligrams per kilogram \[mg/kg\] and participants 2-11 years of age received 10-15 mg/kg) once daily for 9 months (240 to 270 total doses).
|
3RPT/INH
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV-infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral rifapentine (RPT) tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by Directly Observed Therapy (DOT), defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Overall Study
Ineligible for Study
|
163
|
159
|
|
Overall Study
Out of Window
|
129
|
69
|
|
Overall Study
Death
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
66
|
54
|
|
Overall Study
Adverse Event
|
139
|
196
|
|
Overall Study
Lost to Follow-up
|
293
|
60
|
|
Overall Study
Physician Decision
|
49
|
21
|
|
Overall Study
Refused Treatment (continued follow-up)
|
225
|
224
|
|
Overall Study
Pregnant
|
53
|
20
|
|
Overall Study
Other
|
204
|
69
|
Baseline Characteristics
Three Months of Weekly Rifapentine and Isoniazid for M. Tuberculosis Infection
Baseline characteristics by cohort
| Measure |
9INH
n=3908 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) once daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4145 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
Total
n=8053 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
35 years
n=5 Participants
|
36 years
n=7 Participants
|
35 years
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
1812 participants
n=5 Participants
|
1847 participants
n=7 Participants
|
3659 participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
2096 participants
n=5 Participants
|
2297 participants
n=7 Participants
|
4393 participants
n=5 Participants
|
|
Sex/Gender, Customized
Missing
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Month 33Population: Modified Intention-to-Treat (MITT) Population: all participants who enrolled in study and were eligible (Ineligible=source TB case resistant to INH or rifampin; source TB case culture-negative for MTB; positive TST not confirmed; MTB drug susceptibility test results not available for source TB case; or TB disease at enrollment).
Cumulative TB disease rate defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for Mycobacterium tuberculosis \[MTB\]) and those \<18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, computed tomography \[CT\] scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for acid-fast bacilli \[AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants with (w/)33 months of follow-up calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=3745 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3986 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants Less Than [<]18 Years of Age at 33 Months After Enrollment
|
0.43 TB cases per 100 participants w/followup
|
0.19 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)Population: MITT Population
Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and those \<18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and 24 months after completion of study therapy per 100 participants with up to 33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=3651 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3914 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture-Confirmed or Probable (Clinical) TB Disease in Participants <18 Years of Age at 24 Months Following Completion of Study Therapy
|
0.37 TB cases per 100 participants w/followup
|
0.16 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to 33 MonthsCumulative TB disease rate was defined as number of participants (regardless of age) with culture-confirmed TB disease (defined as positive culture for MTB\]) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB, or caseating granulomata at autopsy or biopsy) between enrollment and the 990th Day of the Trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=3745 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3986 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Culture-Confirmed or Probable (Clinical) TB Disease (Regardless of Age) At 33 Months After Enrollment
|
0.49 TB cases per 100 participants w/followup
|
0.24 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])Population: Safety Population: all participants who enrolled in the study and took at least 1 dose of study drug.
Discontinuation of study drug due to an adverse drug reaction associated with either 3RPT/INH or 9INH was defined as discontinuing treatment and/or study due to a treatment-related adverse event (AE) (considered either possibly, probably, or definitely related to the study drug by the investigator).
Outcome measures
| Measure |
9INH
n=3759 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4040 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants With Drug Discontinuation Due to Adverse Drug Reactions Associated With 3RPT/INH or 9INH
|
3.8 percentage of participants
|
4.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to 60 days after the last dose of study drug (Month 5 [3RPT/INH] or Month 11 [9INH])Population: Safety Population
Drug toxicities (or AEs) were graded using Common Toxicity Criteria (CTC version 2.0, Publish Date April 30, 1999, Cancer Therapy Evaluation Program). Grade 3 and 4 drug toxicities associated with 3RPT/INH or 9INH were defined as treatment-related Grade 3 or 4 AEs (considered either possibly, probably, or definitely related to the study drug by the investigator).
Outcome measures
| Measure |
9INH
n=3759 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4040 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
Grade 3
|
2.2 percentage of participants
|
2.7 percentage of participants
|
|
Percentage of Patients With Grade 3 or 4 Drug Toxicities Associated With 3RPT/INH or 9INH
Grade 4
|
0.4 percentage of participants
|
0.4 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 35Population: Safety Population
Outcome measures
| Measure |
9INH
n=3759 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4040 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants With Death Due to Any Cause
|
1.0 percentage of participants
|
0.8 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Month 33Among participants concomitantly receiving methadone, the development of methadone withdrawal (defined as having \>3 new symptoms for \>7 days: nausea and vomiting, abdominal cramps, body aches, restlessness, irritability, dilated pupils, tremors, involuntary twitching, lacrimation, rhinorrhea, sneezing, yawning, excessive perspiration, goose flesh, or diarrhea).
Outcome measures
| Measure |
9INH
n=77 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=75 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants With Methadone Withdrawal Associated With 3RPT/INH and 9INH Among Participants Receiving Concomitant Methadone
|
14 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)Population: MITT Population
Drug discontinuations for any reason associated with 3RPT/INH or 9INH included all reasons for discontinuation from study treatment, regardless of relationship to treatment.
Outcome measures
| Measure |
9INH
n=3745 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3986 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants With Drug Discontinuation for Any Reason Associated With 3RPT/INH or 9INH
|
31.0 percentage of participants
|
17.9 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 3 (3RPT/INH) or Month 9 (9INH)Population: MITT Population
Completion in the 3RPT/INH arm was defined as: received 12 doses of RPT/INH within 16 weeks (12 weeks optimal). However, participants were considered to have completed therapy if at least 11 doses of RPT/INH had been received (\~90%) during the 16-week time period. Completion in the 9INH arm was defined as: received 270 doses of INH within 52 weeks (39 weeks optimal). However, participants were considered to have completed therapy if at least 240 doses of INH were received (\~90%) during the 52-week period.
Outcome measures
| Measure |
9INH
n=3745 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3986 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants Who Completed the Treatment Regimen
|
69.0 percentage of participants
|
82.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline up to Month 33Population: Per Protocol Population: all enrolled and eligible participants (MITT Population) who completed study drug within targeted time period (11-12 3RPT/INH doses within 10-16 weeks; 240-270 INH doses within 35-52 weeks) or developed TB disease or died while on study therapy (or follow-up) but completed ≥75% of expected number of doses prior to event.
Cumulative TB disease rate was defined as number of participants ≥18 years old with culture-confirmed TB disease (defined as positive culture for MTB) and \<18 years old with probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and 33 months after enrollment (for those who completed therapy within 33 months) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=2585 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=3273 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Culture-Confirmed TB Disease in Participants ≥18 Years of Age AND Culture Confirmed or Probable (Clinical) TB Disease Among Participants <18 Years of Age Who Completed Study Phase Therapy Within 33 Months of Enrollment
|
0.11 TB cases per 100 participants w/followup
|
0.05 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to Month 33Population: N equals the number of participants who developed active TB disease during the study for which DST was performed.
Drug-susceptibility testing (DST) was performed on isolates of MTB obtained from participants who developed signs and symptoms of active TB disease (including sputum specimens or specimens from appropriate body site for extrapulmonary TB disease). DST was performed at site's local laboratory and sent to Sponsor for confirmatory susceptibility testing. DST included all drugs currently used to treat TB disease, including pyrazinamide (PZA) and fluoroquinolones. Susceptibility was tested for other drugs at the Sponsor laboratory at the following concentrations: INH, 0.02, 1.0, and 5.0 micrograms per milliliter (µg/mL) and rifampin (RIF), 1.0 µg/mL. Isolates resistant to RIF were assumed to be resistant to RPT.
Outcome measures
| Measure |
9INH
n=13 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=7 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
INH monoresistance
|
15 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants With Resistance to Study Medications in Isolates of MTB From Participants Who Developed Active TB Disease Within 33 Months of Enrollment
RIF and PZA resistant
|
0 percentage of participants
|
14 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline to Month 33Cumulative TB disease rate was defined as number of HIV-infected participants ≥2 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=193 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=206 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Culture-Confirmed or Probable TB Disease in HIV-Infected Participants Within 33 Months After Enrollment
|
3.5 TB cases per 100 participants w/followup
|
1.01 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to Month 27 (3RPT/INH) or Month 33 (9INH)Cumulative TB disease rate was defined as number of HIV-infected participants with culture-confirmed TB (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and 24 months after completion of study therapy per 100 participants with up to 33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=185 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=194 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of HIV-Infected Participants With Culture-Confirmed or Probable TB Disease at 24 Months After Completion of Study Therapy
|
3.12 TB cases per 100 participants w/followup
|
1.07 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to Month 33Cumulative TB disease rate was defined as number of participants \<18 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=434 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=471 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Participants <18 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
|
0.74 TB cases per 100 participants w/followup
|
0.00 TB cases per 100 participants w/followup
|
SECONDARY outcome
Timeframe: Baseline up to Month 33Cumulative TB disease rate was defined as number of participants \<12 years old with culture-confirmed TB disease (defined as positive culture for MTB) or probable (clinical) TB disease (defined as objective evidence of clinical TB disease \[cough, fever, night sweats, weight loss, or hemoptysis\] based on history or physical exam plus radiograph, CT scan, other diagnostic tests PLUS response to antituberculosis therapy AND objective improvement of radiograph or other diagnostic tests; OR evidence of granuloma with organism positive for AFB\], or caseating granulomata at autopsy or biopsy) between enrollment and the 990th day of the trial (33 months after enrollment, or end of the trial) per 100 participants w/33 months of follow-up and was calculated using survival analysis methods (Kaplan-Meier approach).
Outcome measures
| Measure |
9INH
n=178 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (aged ≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=234 Participants
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Cumulative Rate of Participants <12 Years Old With Culture-Confirmed or Probable (Clinical) TB Disease Within 33 Months of Enrollment
|
1.35 TB cases per 100 participants w/followup
|
0.00 TB cases per 100 participants w/followup
|
Adverse Events
9INH
3RPT/INH
Serious adverse events
| Measure |
9INH
n=3759 participants at risk
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) once daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4040 participants at risk
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Surgical and medical procedures
Hernia repair
|
0.08%
3/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Hysterectomy
|
0.03%
1/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Ankle operation
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Cholecystectomy
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Abdominal operation
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Abscess drainage
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Alcohol detoxification
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Angioplasty
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Arteriovenous graft
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Cardiac operation
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Endometriosis ablation
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Craniotomy
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Gallbladder operation
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Inguinal hernia repair
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Internal fixation of fracture
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Open reduction of fracture
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Salivary gland resection
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Thyroidectomy
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Transurethral prostatectomy
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Surgical and medical procedures
Varicose vein operation
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Infections and infestations
Cellulitis
|
0.08%
3/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Infections and infestations
Pneumonia
|
0.08%
3/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Infections and infestations
Bronchitis
|
0.05%
2/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Infections and infestations
Appendicitis perforated
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Pyelonephritis
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Infections and infestations
Abdominal wall abscess
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Cholecystitis infective
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Gastroenteritis
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Helicobacter infection
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Kidney infection
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Infections and infestations
Lobar pneumonia
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Meningitis viral
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Pelvic inflammatory disease
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Infections and infestations
Pharyngitis streptococcal
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Sinusitis
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Urinary tract infection
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Infections and infestations
Wound infection
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Abdominal pain
|
0.08%
3/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Pancreatitis
|
0.05%
2/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Vomiting
|
0.05%
2/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.00%
0/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Nausea
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Colitis
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Diverticulum
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Oesophageal irritation
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Periodontal disease
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Depression
|
0.08%
3/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Depression suicidal
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Drug dependence
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Suicidal ideation
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Suicide attempt
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Major depression
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Mental disorder
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Mental status changes
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Substance abuse
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Psychiatric disorders
Suicidal behavior
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Contusion
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Laceration
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Medication error
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Overdose
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Snake bite
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Stab wound
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
General disorders
Chest pain
|
0.19%
7/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
General disorders
Chest discomfort
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
General disorders
Local swelling
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
General disorders
Pyrexia
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
Syncope
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Nervous system disorders
Cerebrovascular accident
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Nervous system disorders
Convulsion
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
Dizziness
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Nervous system disorders
Drug withdrawal convulsions
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
Dysarthria
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Nervous system disorders
Subarachnoid haemorrhage
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
Thalamic infarction
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
Toxic encephalopathy
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Cardiac disorders
Myocardial infarction
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Cardiac disorders
Atrial fibrillation
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Cardiac disorders
Cardiac failure congestive
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Immune system disorders
Hypersensitivity
|
0.03%
1/3759 • Baseline until Month 35
|
0.20%
8/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Pseudoarthrosis
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Hepatobiliary disorders
Hepatitis
|
0.08%
3/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/3759 • Baseline until Month 35
|
0.05%
2/4040 • Baseline until Month 35
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Hepatobiliary disorders
Cholecystitis
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Vascular disorders
Hypertension
|
0.08%
3/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Vascular disorders
Hypertensive crisis
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Vascular disorders
Deep vein thrombosis
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic neoplasm malignant
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic gastric cancer
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Osteosarcoma recurrent
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.03%
1/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Metabolism and nutrition disorders
Gestational diabetes
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Blood and lymphatic system disorders
Anaemia
|
0.08%
3/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.05%
2/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Renal and urinary disorders
Urinary retention
|
0.03%
1/3759 • Baseline until Month 35
|
0.00%
0/4040 • Baseline until Month 35
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3759 • Baseline until Month 35
|
0.02%
1/4040 • Baseline until Month 35
|
Other adverse events
| Measure |
9INH
n=3759 participants at risk
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) self-administered oral INH tablets (≥12 years of age received 5 mg/kg and participants 2-11 years of age received 10-15 mg/kg) once daily for 9 months (240 to 270 total doses).
|
3RPT/INH
n=4040 participants at risk
Participants who were high-risk TST reactors (household and other close contacts of active TB cases, recent \[within 2 years\] tuberculin converters, participants with fibrotic lesions on CXR, HIV infected participants) received oral INH tablets (≥12 years of age received 15 mg/kg and participants 2-11 years of age received 25 mg/kg) and oral RPT tablets (between 300-900 mg based on weight) once per week for 3 months (11 to 12 total doses) administered by DOT, defined as a healthcare worker observing ingestion of each dose of RPT and INH.
|
|---|---|---|
|
Immune system disorders
Hypersensitivity
|
0.45%
17/3759 • Baseline until Month 35
|
3.8%
153/4040 • Baseline until Month 35
|
|
Injury, poisoning and procedural complications
Medication error
|
0.96%
36/3759 • Baseline until Month 35
|
0.67%
27/4040 • Baseline until Month 35
|
|
Hepatobiliary disorders
Hepatitis
|
2.9%
110/3759 • Baseline until Month 35
|
0.59%
24/4040 • Baseline until Month 35
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
1.8%
69/3759 • Baseline until Month 35
|
1.1%
45/4040 • Baseline until Month 35
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place