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Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT01404312
Collaborator
(none)
3,000
Enrollment
45
Locations
2
Arms
65.7
Actual Duration (Months)
66.7
Patients Per Site
1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

HIV-infected people have an increased risk of developing active tuberculosis (TB). At the time the study was designed, the standard course of treatment for TB was 6 to 9 months of isoniazid (INH).This study compared the safety and effectiveness of a 4-week regimen of rifapentine (RPT) plus INH versus a standard 9-month regimen of INH in HIV-infected people who are at risk of developing active TB.

Condition or Disease Intervention/Treatment Phase
  • Drug: Rifapentine (RPT)
  • Drug: Isoniazid (INH)
  • Dietary Supplement: Pyridoxine (Vitamin B6)
 Phase 3

Detailed Description

The World Health Organization (WHO) estimated that in 2017 there were 10 million new cases of TB, and 1.6 million people died as a result of TB. Among new TB cases, it is estimated that 920,000 occurred in people who were HIV-coinfected, and 23% of TB deaths were among HIV-coinfected individuals. In Africa, TB is the leading AIDS-related opportunistic infection. Latent TB infection occurs when people are infected with the bacteria that cause TB, but they do not have any symptoms of TB infection. Latent TB can develop into active TB, and HIV-infected people have an increased risk of progressing from latent TB to active TB. INH is a medication that is prescribed for people with latent TB to help prevent active TB from developing. The standard INH treatment regimen is 6 to 9 months; a shorter treatment regimen of 3 months of once-weekly RPT plus INH has proven to be as effective and improved adherence. The purpose of this study was to compare the safety and effectiveness of a 4-week daily regimen of RPT plus INH to a standard 9-month daily INH regimen for TB prevention in HIV-infected individuals.

This study enrolled HIV-infected people who did not have evidence of active TB but who were at high risk of developing active TB. Participants were randomly assigned to receive RPT and INH once a day for 4 weeks or INH once a day for 9 months. All participants received pyridoxine (vitamin B6) with each dose of INH to help prevent possible side effects. Study visits occurred at baseline and Weeks 2, 4, 8, 12, 16, 20, 24, and 36. At select study visits, participants had a physical exam, clinical assessment, blood collection, and a chest radiograph or chest computed tomography (CT) scan (if needed). Some participants had their blood stored for future testing. Follow-up study visits occurred every 12 weeks starting at Week 48 and continued for 3 years after the last participant enrolled.

Study Design

Study Type:
Interventional
Actual Enrollment :
3000 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
Official Title:
Phase III Clinical Trial of Ultra-Short-Course Rifapentine/Isoniazid for the Prevention of Active Tuberculosis in HIV-Infected Individuals With Latent Tuberculosis Infection
Actual Study Start Date :
May 23, 2012
Actual Primary Completion Date :
Nov 14, 2017
Actual Study Completion Date :
Nov 14, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: RPT plus INH Regimen (Arm A)

Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications.

Drug: Rifapentine (RPT)
RPT dosing was be based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg received 600 mg once daily (administered as four 150-mg tablets).

Drug: Isoniazid (INH)
Participants received one 300-mg tablet or three 100-mg tablets of INH once daily.

Dietary Supplement: Pyridoxine (Vitamin B6)
Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants who received 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants who received 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Active Comparator: INH Regimen (Arm B)

Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36.

Drug: Isoniazid (INH)
Participants received one 300-mg tablet or three 100-mg tablets of INH once daily.

Dietary Supplement: Pyridoxine (Vitamin B6)
Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants who received 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants who received 50 mg of pyridoxine took two 25-mg tablets once daily with INH.

Outcome Measures

Primary Outcome Measures

  1. Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause [From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

    Incidence rate (events per 100 person-years) was estimated, and 95.1% confidence interval used to account for interim analysis of primary efficacy outcome.

Secondary Outcome Measures

  1. Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs [From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

    Occurrence of any SAE that meets the ICH definition of an SAE

  2. Number of Participants With a Targeted Adverse Event [From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

    Targeted adverse events include each new grade 3 or 4 laboratory value or sign or symptom that is at least one grade increase from baseline for the following: nausea and vomiting; cutaneous; drug-associated fever; elevated aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]), or bilirubin; and peripheral neuropathy

  3. Number of Participants in Each Category of Ordered Categorical Variable Indicating Most Stringent Level of Study Drug Management Due to Toxicity That Was Required Over the Treatment Period [From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)]

    Ordered categories include: Premature permanent treatment discontinuation Treatment hold for more than 7 consecutive days None of the above

  4. Cumulative Incidence of Death From Any Cause [From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

    Data table estimates for percentage who died by each time point were estimated using Kaplan-Meier at 1, 2, 3, and 4 years post-entry.

  5. Cumulative Incidence of Death Due to a Non-TB Event [From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)]

    Cumulative incidence function estimated nonparametrically, treating TB-related deaths as competing risks.

  6. Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis [After TB diagnosis]

    Among MTB-diagnosed participants who underwent drug-susceptibility testing, the number who had any resistance to a particular drug.

  7. Efavirenz (EFV) Plasma Concentrations in Arm A [Measured at Weeks 0, 2, 4, and 16]

    Mean and standard deviation. Week 16 samples have not yet been analyzed because the metabolite assay is being validated, and requires submission for approval by the Clinical Pharmacology Quality Assurance Program. Analysis of week 16 samples are anticipated to be available in September 2019.

  8. Nevirapine (NVP) Plasma Concentrations in Arm A [Measured at Weeks 0, 2, and 4]

    Mean and standard deviation

  9. EFV Plasma Concentrations in Arm B [Measured at weeks 0, 2 and 4]

    For Version 2.0 of the protocol only, measured in the first 90 participants randomized to Arm B who enter the study taking EFV and who meet dose timing criteria. Outcome measure was not assessed because no participants enrolled under version 2.0 of the protocol were on Efavirenz at study entry.

Eligibility Criteria

Criteria

Ages Eligible for Study:
13 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • HIV-1 infection

  • Tuberculin skin test (TST) reactivity greater than or equal to 5 mm or a positive interferon gamma release assay (IGRA) at any time prior to study entry, OR living in a high TB burden area. More information on this criterion can be found in the protocol.

  • Laboratory values obtained within 30 days prior to study entry:

  1. Absolute neutrophil count (ANC) greater than 750 cells/mm^3

  2. Hemoglobin greater than or equal to 7.4 g/dL

  3. Platelet count greater than or equal to 50,000/mm^3

  4. AST (SGOT) and ALT (SGPT) less than or equal to three times the upper limit of normal (ULN)

  5. Total bilirubin less than or equal to 2.5 times the ULN

  • Chest radiograph or chest CT scan without evidence of active tuberculosis, unless one has been performed within 30 days prior to entry

  • Female participants of reproductive potential must have a negative serum or urine pregnancy test performed within 7 days prior to study entry. More information on this criterion can be found in the protocol.

  • All participants must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization) while receiving RPT and for 6 weeks after stopping this drug

  • Female participants who are participating in sexual activity that could lead to pregnancy must agree to use one reliable non-hormonal form of contraceptive while receiving RPT and for 6 weeks after stopping this drug. More information on this criterion can be found in the protocol.

  • Weight of greater than or equal to 30 kg

  • Participant or legal guardian is able and willing to provide informed consent

Exclusion Criteria:

  • Treatment for active or latent TB (pulmonary or extrapulmonary) within 2 years prior to study entry or, at screening, presence of any confirmed or probable TB based on criteria listed in the current ACTG Diagnosis Appendix

  • History of multi-drug resistant (MDR) or extensively-drug resistant (XDR) TB at any time prior to study entry

  • Known exposure to MDR or XDR TB (e.g., household member of a person with MDR or XDR TB) at any time prior to study entry

  • Treatment for more than 14 consecutive days with a rifamycin or more than 30 consecutive days with INH at any time during the 2 years prior to enrollment

  • For participants taking antiretroviral therapy (ART) at study entry, only approved nucleoside reverse transcriptase inhibitors (NRTIs) with efavirenz (EFV) or nevirapine (NVP) for at least 4 weeks were permitted

  • History of liver cirrhosis at any time prior to study entry.

  • Evidence of acute hepatitis, such as abdominal pain, jaundice, dark urine, and/or light stools within 90 days prior to study entry

  • Diagnosis of porphyria at any time prior to study entry

  • Peripheral neuropathy greater than or equal to Grade 2 according to the December 2004 (Clarification, August 2009) Division of AIDS (DAIDS) Toxicity Table, within 90 days prior to study entry

  • Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation

  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements

  • Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry

  • Breastfeeding

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program La Jolla California United States 92093-0672
2 University of Southern California CRS Los Angeles California United States 90033-1079
3 UCSD Antiviral Research Center CRS San Diego California United States 92103
4 Ucsf Hiv/Aids Crs San Francisco California United States 94110
5 Harbor-UCLA CRS Torrance California United States 90502
6 University of Colorado Hospital CRS Aurora Colorado United States 80045
7 Denver Public Health CRS Denver Colorado United States 80204
8 The University of Miami AIDS Clinical Research Unit (ACRU) CRS Miami Florida United States 33136
9 Northwestern University CRS Chicago Illinois United States 60611
10 Boston Medical Center CRS Boston Massachusetts United States 02118
11 Henry Ford Hosp. CRS Detroit Michigan United States 48202
12 Cooper Univ. Hosp. CRS Camden New Jersey United States 08103
13 New Jersey Medical School Clinical Research Center CRS Newark New Jersey United States 07103
14 Bronx-Lebanon Hospital Center NICHD CRS Bronx New York United States 10457
15 Nyu Ny Nichd Crs New York New York United States 10016
16 Columbia P&S CRS New York New York United States 10032-3732
17 Chapel Hill CRS Chapel Hill North Carolina United States 27599
18 Duke University Medical Center CRS Durham North Carolina United States 27710
19 Trinity Health and Wellness Center CRS Dallas Texas United States 75208
20 Houston AIDS Research Team CRS Houston Texas United States 77030
21 University of Washington AIDS CRS Seattle Washington United States 98104-9929
22 Gaborone CRS Gaborone Botswana
23 Molepolole CRS Gaborone Botswana
24 Hospital Nossa Senhora da Conceicao CRS Porto Alegre Rio Grande Do Sul Brazil 91350-200
25 Univ. of Sao Paulo Brazil NICHD CRS Sao Paulo São Paulo Brazil 14049-900
26 Hospital Federal dos Servidores do Estado NICHD CRS Rio de Janeiro Brazil 20221-903
27 Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS Rio de Janeiro Brazil 21040-360
28 Hosp. Geral De Nova Igaucu Brazil NICHD CRS Rio de Janeiro Brazil 26030
29 Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS Sao Paulo Brazil 01246-900
30 Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS Port-au-Prince Haiti 6110
31 GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS Port-au-Prince Haiti
32 Kisumu Crs Kisumu Nyanza Kenya 40100
33 Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS Kericho Rift Valley Kenya 20200
34 Moi University Clinical Research Center (MUCRC) CRS Eldoret Kenya 30100
35 Malawi CRS Lilongwe Central Malawi
36 Blantyre CRS Blantyre Malawi
37 Barranco CRS Lima Peru 04
38 San Miguel CRS Lima Peru 32
39 Soweto ACTG CRS Johannesburg Gauteng South Africa 1862
40 Wits Helen Joseph Hospital CRS (Wits HJH CRS) Johannesburg Gauteng South Africa 2092
41 Durban International Clinical Research Site CRS Durban KwaZulu-Natal South Africa 4013
42 Thai Red Cross AIDS Research Centre (TRC-ARC) CRS Bangkok Thailand 10330
43 Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS Chiang Mai Thailand 50200
44 Chonburi Hosp. CRS Chon Buri Thailand 20000
45 Parirenyatwa CRS Harare Zimbabwe

Sponsors and Collaborators

  • National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Richard E. Chaisson, MD, Johns Hopkins University
  • Study Chair: Susan Swindells, MBBS, University of Nebraska

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01404312
Other Study ID Numbers:
  • A5279
  • 10848
  • ACTG A5279
First Posted:
Jul 28, 2011
Last Update Posted:
Nov 4, 2021
Last Verified:
Dec 1, 2020
Additional relevant MeSH terms:
Infections
Tuberculosis
Pyridoxine
Pyridoxal
Vitamin B 6
Isoniazid
Rifapentine

Study Results

Participant Flow

Recruitment Details Forty-five Clinical Research sites across 10 countries participated in the study. The first participant was randomized on May 23, 2012. Accrual closed on November 12, 2014 with 3,000 participants enrolled in the study.
Pre-assignment Detail Randomization was 1:1, and stratified by CD4 count (< 100, 100-250, and > 250 cells/mm^3), and antiretroviral therapy status (receiving antiretroviral therapy or not receiving antiretroviral therapy at enrollment).
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Period Title: Overall Study
STARTED 1496 1504
COMPLETED 1198 1193
NOT COMPLETED 298 311

Baseline Characteristics

Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B) Total
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH. Total of all reporting groups
Overall Participants 1496 1504 3000
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
35.7
(10.3)
35.6
(10.3)
35.7
(10.3)
Age, Customized (Count of Participants)
<=20 years
77
5.1%
70
4.7%
147
4.9%
>20, <=30 years
421
28.1%
455
30.3%
876
29.2%
>30, <=40 years
523
35%
514
34.2%
1037
34.6%
>40, <=50 years
342
22.9%
331
22%
673
22.4%
>50 years
133
8.9%
134
8.9%
267
8.9%
Sex: Female, Male (Count of Participants)
Female
802
53.6%
812
54%
1614
53.8%
Male
694
46.4%
692
46%
1386
46.2%
Race/Ethnicity, Customized (Count of Participants)
White Non-Hispanic
16
1.1%
12
0.8%
28
0.9%
Black Non-Hispanic
992
66.3%
991
65.9%
1983
66.1%
Hispanic (Regardless of Race)
361
24.1%
369
24.5%
730
24.3%
Asian, Pacific Islander
122
8.2%
128
8.5%
250
8.3%
Not Reported
5
0.3%
4
0.3%
9
0.3%
Region of Enrollment (participants) [Number]
Haiti
198
13.2%
198
13.2%
396
13.2%
United States
45
3%
46
3.1%
91
3%
Malawi
106
7.1%
108
7.2%
214
7.1%
Botswana
210
14%
212
14.1%
422
14.1%
Brazil
102
6.8%
98
6.5%
200
6.7%
South Africa
307
20.5%
309
20.5%
616
20.5%
Zimbabwe
56
3.7%
58
3.9%
114
3.8%
Kenya
93
6.2%
94
6.3%
187
6.2%
Thailand
121
8.1%
124
8.2%
245
8.2%
Peru
258
17.2%
257
17.1%
515
17.2%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
24.6
(5.2)
24.5
(5.3)
24.5
(5.2)
IV Drug Use (Count of Participants)
Never
1489
99.5%
1497
99.5%
2986
99.5%
Currently
2
0.1%
1
0.1%
3
0.1%
Previously
5
0.3%
6
0.4%
11
0.4%
Prior Tuberculosis History (Count of Participants)
Yes
82
5.5%
89
5.9%
171
5.7%
No
1414
94.5%
1415
94.1%
2829
94.3%
Screening CD4 counts (Count of Participants)
<100 cells/mm^3
37
2.5%
37
2.5%
74
2.5%
>=100,<=250 cells/mm^3
160
10.7%
165
11%
325
10.8%
>250 cells/mm^3
1299
86.8%
1302
86.6%
2601
86.7%
Antiretroviral Therapy (ART) at Entry (Count of Participants)
Efavirenz-based
650
43.4%
649
43.2%
1299
43.3%
Nevirapine-based
97
6.5%
100
6.6%
197
6.6%
Neither Efavirenz nor Nevirapine-based
3
0.2%
6
0.4%
9
0.3%
Not on ART
746
49.9%
749
49.8%
1495
49.8%
HIV-1 RNA Viral load among participants on ART at entry (Count of Participants)
Detectable
154
10.3%
143
9.5%
297
9.9%
Undetectable
569
38%
586
39%
1155
38.5%
Not Reported
27
1.8%
26
1.7%
53
1.8%

Outcome Measures

1. Primary Outcome
Title Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause
Description Incidence rate (events per 100 person-years) was estimated, and 95.1% confidence interval used to account for interim analysis of primary efficacy outcome.
Time Frame From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

Outcome Measure Data

Analysis Population Description
All participants who started study treatment.
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
Number (95.1% Confidence Interval) [Events per 100 person-years]
0.6506
0.6736
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments Mantel-Haenszel method used for estimating standardized incidence rate in each arm and incidence rate difference.
Type of Statistical Test Non-Inferiority
Comments Non-inferiority margin: 1.25 events per 100 person-years. Sample size determination was based on the assumption of a primary endpoint rate of 2.0/100 person-years, with a one-sided 0.025 alpha level, and targeting at least 90% power. This required a sample size of approximately 2500. The sample size was adjusted upwards to account for loss to follow-up, interim monitoring, and to allow for subgroup analyses with reasonable power.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Incidence Rate Difference
Estimated Value -0.0231
Confidence Interval (2-Sided) 95.1%
-0.346 to 0.300
Parameter Dispersion Type:
Value:
Estimation Comments Estimate given as Incidence rate in Arm A - Incidence Rate in Arm B (negative favors Arm A). Incidence rate units: Events per 100 person-years
2. Secondary Outcome
Title Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs
Description Occurrence of any SAE that meets the ICH definition of an SAE
Time Frame From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

Outcome Measure Data

Analysis Population Description
All participants who started study treatment
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
No SAE occurred
1405
93.9%
1390
92.4%
At least one SAE occurred
83
5.5%
108
7.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments Comparison of the proportion of participants with any SAE occurrence between arms A and B. H0: Proportion of participants with SAE in Arm A = Proportion of participants with SAE in Arm B.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.073
Comments Not adjusted for multiple comparisons.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.016
Confidence Interval (2-Sided) 95%
-0.035 to 0.002
Parameter Dispersion Type:
Value:
Estimation Comments Estimate given as: Proportion Arm A - Proportion Arm B
3. Secondary Outcome
Title Number of Participants With a Targeted Adverse Event
Description Targeted adverse events include each new grade 3 or 4 laboratory value or sign or symptom that is at least one grade increase from baseline for the following: nausea and vomiting; cutaneous; drug-associated fever; elevated aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]), or bilirubin; and peripheral neuropathy
Time Frame From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

Outcome Measure Data

Analysis Population Description
All participants who started study treatment
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
No Targeted Safety Event
1445
96.6%
1446
96.1%
Occurrence of Targeted Safety Event
43
2.9%
52
3.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments Comparison of the proportion of participants with any targeted adverse event occurrence between arms A and B. H0: Proportion of participants with a targeted adverse event in Arm A = Proportion of participants with a targeted adverse event in Arm B.
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.405
Comments Not adjusted for multiple comparisons
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -.0058
Confidence Interval (2-Sided) 95%
-0.019 to 0.007
Parameter Dispersion Type:
Value:
Estimation Comments Estimate given as: Proportion Arm A - Proportion Arm B
4. Secondary Outcome
Title Number of Participants in Each Category of Ordered Categorical Variable Indicating Most Stringent Level of Study Drug Management Due to Toxicity That Was Required Over the Treatment Period
Description Ordered categories include: Premature permanent treatment discontinuation Treatment hold for more than 7 consecutive days None of the above
Time Frame From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)

Outcome Measure Data

Analysis Population Description
All participants who started study treatment
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
Premature permanent treatment discontinuation
16
1.1%
25
1.7%
Treatment held for more than 7 days
11
0.7%
31
2.1%
None of the above
1461
97.7%
1442
95.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments Odds ratio of being in higher category estimated from proportional odds model H0: Odds ratio of being in higher category for Arm A vs Arm B = 1
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.093
Confidence Interval (2-Sided) 95%
1.315 to 3.332
Parameter Dispersion Type:
Value:
Estimation Comments Estimate given as: Odds of being in higher category (more stringent management due to toxicity) for Arm B compared with arm A Not adjusted for multiple comparisons.
5. Secondary Outcome
Title Cumulative Incidence of Death From Any Cause
Description Data table estimates for percentage who died by each time point were estimated using Kaplan-Meier at 1, 2, 3, and 4 years post-entry.
Time Frame From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

Outcome Measure Data

Analysis Population Description
All Participants who started study treatment
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
1 year post-entry
0.35
0%
0.63
0%
2 years post-entry
0.49
0%
1.15
0.1%
3 years post-entry
1.05
0.1%
1.62
0.1%
4 years post-entry
2.00
0.1%
2.29
0.2%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments H0: Survival curve Arm A = Survival curve Arm B
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.3078
Comments Not adjusted for multiple comparisons
Method Log Rank
Comments
6. Secondary Outcome
Title Cumulative Incidence of Death Due to a Non-TB Event
Description Cumulative incidence function estimated nonparametrically, treating TB-related deaths as competing risks.
Time Frame From entry to occurrence of event, up to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)

Outcome Measure Data

Analysis Population Description
All participants who started study treatment
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 1488 1498
Cumulative incidence by 1 year post-randomization
0.3
0%
0.5
0%
Cumulative incidence by 2 years post-randomization
0.4
0%
1.0
0.1%
Cumulative incidence by 3 years post-randomization
0.9
0.1%
1.5
0.1%
Cumulative incidence by 4 years post-randomization
1.6
0.1%
2.0
0.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RPT Plus INH Regimen (Arm A), INH Regimen (Arm B)
Comments Competing risk analysis using the Fine-Gray model, treating TB-related deaths as competing risks, and other deaths including deaths of unknown cause as the event of interest. H0: Hazard Ratio for Arm A vs Arm B = 1
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.2802
Comments Not adjusted for multiple comparisons
Method Hazard Ratio
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.396
Confidence Interval (2-Sided) 95%
0.762 to 2.559
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio given as: Arm B hazard / Arm A hazard, i.e. HR > 1 favors arm A
7. Secondary Outcome
Title Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis
Description Among MTB-diagnosed participants who underwent drug-susceptibility testing, the number who had any resistance to a particular drug.
Time Frame After TB diagnosis

Outcome Measure Data

Analysis Population Description
Participants with a culture-confirmed TB diagnosis who underwent drug susceptibility testing
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily. Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 15 12
Developed Resistance
1
0.1%
1
0.1%
Did not Develop Resistance
14
0.9%
11
0.7%
Developed Resistance
2
0.1%
1
0.1%
Did not Develop Resistance
12
0.8%
11
0.7%
Developed Resistance
0
0%
1
0.1%
Did not Develop Resistance
7
0.5%
7
0.5%
Developed Resistance
0
0%
0
0%
Did not Develop Resistance
6
0.4%
6
0.4%
8. Secondary Outcome
Title Efavirenz (EFV) Plasma Concentrations in Arm A
Description Mean and standard deviation. Week 16 samples have not yet been analyzed because the metabolite assay is being validated, and requires submission for approval by the Clinical Pharmacology Quality Assurance Program. Analysis of week 16 samples are anticipated to be available in September 2019.
Time Frame Measured at Weeks 0, 2, 4, and 16

Outcome Measure Data

Analysis Population Description
Only measured in the first 90 participants randomized to Arm A who entered the study taking EFV and who meet dose timing criteria; and, under Version 2.0 of the protocol, at Weeks 0, 2, 4, and 16 in the first 30 participants randomized to Arm A who enter the study taking EFV and who meet dose timing criteria.
Arm/Group Title RPT Plus INH Regimen (Arm A)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily.
Measure Participants 111
Week 0
3787
(4922)
Week 2
3870
(7011)
Week 4
4082
(4916)
9. Secondary Outcome
Title Nevirapine (NVP) Plasma Concentrations in Arm A
Description Mean and standard deviation
Time Frame Measured at Weeks 0, 2, and 4

Outcome Measure Data

Analysis Population Description
Only measured in the first 90 participants randomized to Arm A who enter the study taking NVP and who meet dose timing criteria. For weeks 0, 2, 4, some samples were missing or contaminated.
Arm/Group Title RPT Plus INH Regimen (Arm A)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg will receive 600 mg once daily (administered as four 150-mg tablets). Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily.
Measure Participants 90
Week0
7573
(3789)
Week 2
6234
(4283)
Week 4
5797
(3963)
10. Secondary Outcome
Title EFV Plasma Concentrations in Arm B
Description For Version 2.0 of the protocol only, measured in the first 90 participants randomized to Arm B who enter the study taking EFV and who meet dose timing criteria. Outcome measure was not assessed because no participants enrolled under version 2.0 of the protocol were on Efavirenz at study entry.
Time Frame Measured at weeks 0, 2 and 4

Outcome Measure Data

Analysis Population Description
Outcome measure was not assessed because no participants enrolled under version 2.0 of the protocol were on Efavirenz at study entry.
Arm/Group Title INH Regimen (Arm B)
Arm/Group Description Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
Measure Participants 0

Adverse Events

Time Frame From entry to end of follow-up 3 years after last participant enrolled (median follow-up time: 3.3 years)
Adverse Event Reporting Description At entry, all diagnoses, signs/symptoms, and laboratory values of all grades that occurred 30 days before entry were collected; post-entry, all diagnoses regardless of grade, signs/symptoms of grade 3 or higher, laboratory values grade 3 or higher, and all events that led to a change in treatment were collected. The DAIDS AE Grading Table (V1.0) and Expedited AE Manual (V2.0) were used.
Arm/Group Title RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Arm/Group Description Participants received RPT (dosage based on their weight), 300 mg of INH, and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 4. During Weeks 5 to 36, participants did not receive any study medications. Rifapentine (RPT): RPT dosing was based on participants' weight: Participants who weighed 30 kg to less than 35 kg received 300 mg once daily (administered as two 150-mg tablets). Participants who weighed 35 kg to less than 45 kg received 450 mg once daily (administered as three 150-mg tablets). Participants who weighed greater than 45 kg received 600 mg once daily (administered as four 150-mg tablets). Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily INH Regimen (Arm B) Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. Isoniazid (INH): Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. Pyridoxine (Vitamin B6): Participants received 25 mg or 50 mg of pyridoxine, based on the current local, national, or international dosing guidelines. Participants receiving 25 mg of pyridoxine took one 25-mg tablet once daily with INH. Participants receiving 50 mg of pyridoxine took two 25-mg tablets once daily with INH.
All Cause Mortality
RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 21/1496 (1.4%) 27/1504 (1.8%)
Serious Adverse Events
RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 40/1496 (2.7%) 68/1504 (4.5%)
Blood and lymphatic system disorders
Anaemia 2/1496 (0.1%) 3/1504 (0.2%)
Neutropenia 5/1496 (0.3%) 0/1504 (0%)
Thrombocytopenia 0/1496 (0%) 1/1504 (0.1%)
Cardiac disorders
Bundle branch block right 0/1496 (0%) 1/1504 (0.1%)
Gastrointestinal disorders
Abdominal pain 0/1496 (0%) 1/1504 (0.1%)
Anal fistula 0/1496 (0%) 1/1504 (0.1%)
Ascites 0/1496 (0%) 1/1504 (0.1%)
Haematemesis 0/1496 (0%) 1/1504 (0.1%)
Inguinal hernia 0/1496 (0%) 1/1504 (0.1%)
Intestinal obstruction 0/1496 (0%) 2/1504 (0.1%)
Umbilical hernia, obstructive 0/1496 (0%) 1/1504 (0.1%)
Vomiting 1/1496 (0.1%) 1/1504 (0.1%)
General disorders
Death 1/1496 (0.1%) 2/1504 (0.1%)
Hepatobiliary disorders
Cholelithiasis 0/1496 (0%) 1/1504 (0.1%)
Drug-induced liver injury 1/1496 (0.1%) 2/1504 (0.1%)
Hepatitis 1/1496 (0.1%) 0/1504 (0%)
Hepatitis acute 0/1496 (0%) 1/1504 (0.1%)
Hepatotoxicity 2/1496 (0.1%) 0/1504 (0%)
Hypertransaminasaemia 0/1496 (0%) 1/1504 (0.1%)
Infections and infestations
Abscess jaw 0/1496 (0%) 1/1504 (0.1%)
Acute hepatitis B 1/1496 (0.1%) 0/1504 (0%)
Bacterial sepsis 1/1496 (0.1%) 0/1504 (0%)
Bone tuberculosis 0/1496 (0%) 1/1504 (0.1%)
Breast abscess 0/1496 (0%) 1/1504 (0.1%)
Cellulitis 0/1496 (0%) 1/1504 (0.1%)
Dengue haemorrhagic fever 0/1496 (0%) 1/1504 (0.1%)
Disseminated tuberculosis 0/1496 (0%) 2/1504 (0.1%)
Encephalitis 0/1496 (0%) 1/1504 (0.1%)
Gastroenteritis 1/1496 (0.1%) 1/1504 (0.1%)
HIV infection 0/1496 (0%) 1/1504 (0.1%)
Orchitis 1/1496 (0.1%) 0/1504 (0%)
Pneumocystis jirovecii pneumonia 0/1496 (0%) 1/1504 (0.1%)
Pneumonia 1/1496 (0.1%) 2/1504 (0.1%)
Retroviral infection 0/1496 (0%) 1/1504 (0.1%)
Septic shock 1/1496 (0.1%) 0/1504 (0%)
Typhus 0/1496 (0%) 1/1504 (0.1%)
Injury, poisoning and procedural complications
Ankle fracture 1/1496 (0.1%) 0/1504 (0%)
Craniocerebral injury 0/1496 (0%) 1/1504 (0.1%)
Incisional hernia 0/1496 (0%) 1/1504 (0.1%)
Jaw fracture 0/1496 (0%) 1/1504 (0.1%)
Rib fracture 0/1496 (0%) 1/1504 (0.1%)
Skin laceration 0/1496 (0%) 1/1504 (0.1%)
Stab wound 1/1496 (0.1%) 0/1504 (0%)
Investigations
Blood alkaline phosphatase increased 0/1496 (0%) 1/1504 (0.1%)
Blood bilirubin increased 0/1496 (0%) 1/1504 (0.1%)
Blood creatinine increased 1/1496 (0.1%) 0/1504 (0%)
Haemoglobin decreased 0/1496 (0%) 1/1504 (0.1%)
Hepatic enzyme increased 1/1496 (0.1%) 7/1504 (0.5%)
Transaminases increased 2/1496 (0.1%) 0/1504 (0%)
Metabolism and nutrition disorders
Dehydration 2/1496 (0.1%) 0/1504 (0%)
Hypoglycaemia 0/1496 (0%) 1/1504 (0.1%)
Musculoskeletal and connective tissue disorders
Arthritis reactive 1/1496 (0.1%) 0/1504 (0%)
Back pain 1/1496 (0.1%) 0/1504 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma 0/1496 (0%) 1/1504 (0.1%)
Hepatocellular carcinoma 2/1496 (0.1%) 0/1504 (0%)
Lymphoma 0/1496 (0%) 1/1504 (0.1%)
Nervous system disorders
Cerebellar ischaemia 0/1496 (0%) 1/1504 (0.1%)
Epilepsy 0/1496 (0%) 1/1504 (0.1%)
Idiopathic intracranial hypertension 0/1496 (0%) 1/1504 (0.1%)
Presyncope 0/1496 (0%) 1/1504 (0.1%)
Seizure 0/1496 (0%) 4/1504 (0.3%)
Subarachnoid haemorrhage 0/1496 (0%) 1/1504 (0.1%)
Superior sagittal sinus thrombosis 1/1496 (0.1%) 0/1504 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion incomplete 0/1496 (0%) 2/1504 (0.1%)
Abortion spontaneous 0/1496 (0%) 1/1504 (0.1%)
Psychiatric disorders
Bipolar disorder 0/1496 (0%) 1/1504 (0.1%)
Suicide attempt 2/1496 (0.1%) 1/1504 (0.1%)
Renal and urinary disorders
Renal impairment 1/1496 (0.1%) 0/1504 (0%)
Reproductive system and breast disorders
Menorrhagia 0/1496 (0%) 1/1504 (0.1%)
Ovarian cyst 0/1496 (0%) 1/1504 (0.1%)
Postmenopausal haemorrhage 0/1496 (0%) 1/1504 (0.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea 0/1496 (0%) 1/1504 (0.1%)
Skin and subcutaneous tissue disorders
Angioedema 1/1496 (0.1%) 1/1504 (0.1%)
Dermatitis allergic 1/1496 (0.1%) 0/1504 (0%)
Diabetic foot 1/1496 (0.1%) 0/1504 (0%)
Rash 2/1496 (0.1%) 1/1504 (0.1%)
Vascular disorders
Hypovolaemic shock 0/1496 (0%) 1/1504 (0.1%)
Other (Not Including Serious) Adverse Events
RPT Plus INH Regimen (Arm A) INH Regimen (Arm B)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1051/1496 (70.3%) 1042/1504 (69.3%)
Gastrointestinal disorders
Abdominal pain 81/1496 (5.4%) 83/1504 (5.5%)
Diarrhoea 101/1496 (6.8%) 108/1504 (7.2%)
General disorders
Pyrexia 198/1496 (13.2%) 187/1504 (12.4%)
Infections and infestations
Nasopharyngitis 93/1496 (6.2%) 84/1504 (5.6%)
Pharyngitis 89/1496 (5.9%) 57/1504 (3.8%)
Tonsillitis 79/1496 (5.3%) 65/1504 (4.3%)
Upper respiratory tract infection 118/1496 (7.9%) 117/1504 (7.8%)
Investigations
Alanine aminotransferase increased 102/1496 (6.8%) 121/1504 (8%)
Aspartate aminotransferase increased 94/1496 (6.3%) 118/1504 (7.8%)
Blood albumin decreased 97/1496 (6.5%) 125/1504 (8.3%)
Blood alkaline phosphatase increased 99/1496 (6.6%) 99/1504 (6.6%)
Blood pressure increased 83/1496 (5.5%) 63/1504 (4.2%)
Blood sodium decreased 219/1496 (14.6%) 200/1504 (13.3%)
Blood sodium increased 87/1496 (5.8%) 107/1504 (7.1%)
Haemoglobin decreased 112/1496 (7.5%) 120/1504 (8%)
Neutrophil count decreased 189/1496 (12.6%) 146/1504 (9.7%)
Weight decreased 74/1496 (4.9%) 105/1504 (7%)
Nervous system disorders
Headache 155/1496 (10.4%) 149/1504 (9.9%)
Pregnancy, puerperium and perinatal conditions
Pregnancy 93/1496 (6.2%) 102/1504 (6.8%)
Respiratory, thoracic and mediastinal disorders
Cough 254/1496 (17%) 238/1504 (15.8%)
Nasal congestion 125/1496 (8.4%) 123/1504 (8.2%)
Oropharyngeal pain 202/1496 (13.5%) 166/1504 (11%)
Rhinorrhoea 122/1496 (8.2%) 130/1504 (8.6%)
Vascular disorders
Hypertension 95/1496 (6.4%) 75/1504 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights

Results Point of Contact

Name/Title ACTG Clinicaltrials.gov Coordinator
Organization ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Phone (301) 628-3313
Email ACTGCT.Gov@s-3.com
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01404312
Other Study ID Numbers:
  • A5279
  • 10848
  • ACTG A5279
First Posted:
Jul 28, 2011
Last Update Posted:
Nov 4, 2021
Last Verified:
Dec 1, 2020