Brief Rifapentine-Isoniazid Evaluation for TB Prevention... | NCT01404312

NCT01404312

ID	Type	Description	Link
10848	Registry Identifier	DAIDS ES Registry Number
ACTG A5279	Other Identifier	Network

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
RPT plus INH Regimen (Arm A)	Experimental	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) Drug: Isoniazid (INH) Dietary Supplement: Pyridoxine (Vitamin B6)
INH Regimen (Arm B)	Active Comparator	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) Dietary Supplement: Pyridoxine (Vitamin B6)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rifapentine (RPT)	Drug	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).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause	Incidence rate (events per 100 person-years) was estimated, and 95.1% confidence interval used to account for interim analysis of primary efficacy outcome.	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)

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs	Occurrence of any SAE that meets the ICH definition of an SAE	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)
Number of Participants With a Targeted Adverse Event

Eligibility Module

Eligibility Criteria

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/Locations Module

Name	Affiliation	Role
Richard E. Chaisson, MD	Johns Hopkins University	Study Chair
Susan Swindells, MBBS	University of Nebraska	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program		La Jolla	California	92093-0672	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
19525621	Background	Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, Gray GE, McIntyre JA, Chaisson RE, Martinson NA. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009 Mar 13;23(5):631-6. doi: 10.1097/QAD.0b013e328327964f.
19729664	Background

Label	URL
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND PEDIATRIC ADVERSE EVENTS VERSION 1.0, DECEMBER, 2004; CLARIFICATION AUGUST 2009	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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. 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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 28, 2014	Nov 14, 2018

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All enrolled participants

Arm/Group Information

ID	Title	Description
BG000	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. 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
BG001	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.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG0000.6506(0.4242 to 0.8770) OG0010.6736(0.4428 to 0.9045)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Mantel-Haenszel method used for estimating standardized incidence rate in each arm and incidence rate difference.					Incidence Rate Difference	-0.0231			2-Sided	95.1	-0.346	0.300			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		Non-Inferiority	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.

Secondary

Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs

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

All participants who started study treatment

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	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. 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.
OG001	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.

Secondary

Number of Participants With a Targeted Adverse Event

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

All participants who started study treatment

Posted

Count of Participants

Participants

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)

ID	Title	Description
OG000	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. 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.

Secondary

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

Ordered categories include:

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

All participants who started study treatment

Posted

Count of Participants

Participants

From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)

ID	Title	Description
OG000	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. 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.
OG001	INH Regimen (Arm B)

Secondary

Cumulative Incidence of Death From Any Cause

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.

All Participants who started study treatment

Posted

Number

events per 100 participants

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)

ID	Title	Description
OG000	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. 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.
OG001	INH Regimen (Arm B)

Secondary

Cumulative Incidence of Death Due to a Non-TB Event

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

All participants who started study treatment

Posted

Number

events per 100 participants

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)

ID	Title	Description
OG000	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. 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.
OG001	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.

Secondary

Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis

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

Participants with a culture-confirmed TB diagnosis who underwent drug susceptibility testing

Posted

Count of Participants

Participants

After TB diagnosis

ID	Title	Description
OG000	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. 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.
OG001	INH Regimen (Arm B)

Secondary

Efavirenz (EFV) Plasma Concentrations in Arm A

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.

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.

Posted

Mean

Standard Deviation

nanograms per mL

Measured at Weeks 0, 2, 4, and 16

ID	Title	Description
OG000	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. 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.

Secondary

Nevirapine (NVP) Plasma Concentrations in Arm A

Mean and standard deviation

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.

Posted

Mean

Standard Deviation

nanograms per mL

Measured at Weeks 0, 2, and 4

ID	Title	Description
OG000	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. 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.

Units	Counts

Secondary

EFV Plasma Concentrations in Arm B

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.

Posted

Measured at weeks 0, 2 and 4

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. 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).	21	1,496	40	1,496	1,051	1,496
EG001	INH Regimen (Arm B)	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.	27	1,504	68	1,504	1,042	1,504

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0013 affected1,504 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0005 affected1,496 at risk EG0010 affected1,504 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Bundle branch block right	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Anal fistula	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Ascites	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0012 affected1,504 at risk
Umbilical hernia, obstructive	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0011 affected1,504 at risk
Death	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0012 affected1,504 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0012 affected1,504 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0010 affected1,504 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Abscess jaw	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Acute hepatitis B	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Bacterial sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Bone tuberculosis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Breast abscess	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Dengue haemorrhagic fever	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Disseminated tuberculosis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0012 affected1,504 at risk
Encephalitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Gastroenteritis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0011 affected1,504 at risk
HIV infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Orchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0012 affected1,504 at risk
Retroviral infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Septic shock	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Typhus	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Incisional hernia	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Jaw fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Stab wound	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Blood bilirubin increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Blood creatinine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Haemoglobin decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Hepatic enzyme increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0017 affected1,504 at risk
Transaminases increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0010 affected1,504 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0010 affected1,504 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Arthritis reactive	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0010 affected1,504 at risk
Lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Cerebellar ischaemia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Epilepsy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Idiopathic intracranial hypertension	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Presyncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Seizure	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0014 affected1,504 at risk
Subarachnoid haemorrhage	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Superior sagittal sinus thrombosis	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Abortion incomplete	Pregnancy, puerperium and perinatal conditions	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0012 affected1,504 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Bipolar disorder	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Suicide attempt	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0011 affected1,504 at risk
Renal impairment	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Menorrhagia	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Ovarian cyst	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Postmenopausal haemorrhage	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0011 affected1,504 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected1,496 at risk EG0010 affected1,504 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected1,496 at risk EG0011 affected1,504 at risk
Hypovolaemic shock	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected1,496 at risk EG0011 affected1,504 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG00081 affected1,496 at risk EG00183 affected1,504 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG000101 affected1,496 at risk EG001108 affected1,504 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG000198 affected1,496 at risk EG001187 affected1,504 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00093 affected1,496 at risk EG00184 affected1,504 at risk
Pharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00089 affected1,496 at risk EG00157 affected1,504 at risk
Tonsillitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG00079 affected1,496 at risk EG00165 affected1,504 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG000118 affected1,496 at risk EG001117 affected1,504 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG000102 affected1,496 at risk EG001121 affected1,504 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00094 affected1,496 at risk EG001118 affected1,504 at risk
Blood albumin decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00097 affected1,496 at risk EG001125 affected1,504 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00099 affected1,496 at risk EG00199 affected1,504 at risk
Blood pressure increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00083 affected1,496 at risk EG00163 affected1,504 at risk
Blood sodium decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG000219 affected1,496 at risk EG001200 affected1,504 at risk
Blood sodium increased	Investigations	MedDRA 21.1	Systematic Assessment	EG00087 affected1,496 at risk EG001107 affected1,504 at risk
Haemoglobin decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG000112 affected1,496 at risk EG001120 affected1,504 at risk
Neutrophil count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG000189 affected1,496 at risk EG001146 affected1,504 at risk
Weight decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG00074 affected1,496 at risk EG001105 affected1,504 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG000155 affected1,496 at risk EG001149 affected1,504 at risk
Pregnancy	Pregnancy, puerperium and perinatal conditions	MedDRA 21.1	Systematic Assessment	EG00093 affected1,496 at risk EG001102 affected1,504 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG000254 affected1,496 at risk EG001238 affected1,504 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG000125 affected1,496 at risk EG001123 affected1,504 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG000202 affected1,496 at risk EG001166 affected1,504 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG000122 affected1,496 at risk EG001130 affected1,504 at risk
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG00095 affected1,496 at risk EG00175 affected1,504 at risk

ID	Term
D014376	Tuberculosis
D015658	HIV Infections

Ancestor Terms

ID	Term
D009164	Mycobacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
C018421	rifapentine
D007538	Isoniazid
D011736	Pyridoxine
D025101	Vitamin B 6

Ancestor Terms

ID	Term
D006834	Hydrazines
D009930	Organic Chemicals
D007539	Isonicotinic Acids
D000147	Acids, Heterocyclic
D006571	Heterocyclic Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D010847	Picolines

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.

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.