TuberculosisPhase 3NCT01404312
Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
A Phase 3 study testing Rifapentine (RPT), Isoniazid (INH) and Pyridoxine (Vitamin B6) in people with Tuberculosis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Tuberculosis, HIV Infections
- What is being tested?
- Rifapentine (RPT), Isoniazid (INH) and Pyridoxine (Vitamin B6)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,000 participants
- Where
- 45 sitesin 10 countries
- Study dates
- 23 May 2012to 14 Nov 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Absolute neutrophil count (ANC) greater than 750 cells/mm^3
- Hemoglobin greater than or equal to 7.4 g/dL
- Platelet count greater than or equal to 50,000/mm^3
Show all 14Show fewer
- AST (SGOT) and ALT (SGPT) less than or equal to three times the upper limit of normal (ULN)
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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
Trial locations and contacts
45 sites in 10 countries.
45 sites in 10 countries
United States21 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80045
Boston Medical Center CRS
Boston, Massachusetts, 02118
Cooper Univ. Hosp. CRS
Camden, New Jersey, 08103
Chapel Hill CRS
Chapel Hill, North Carolina, 27599
Northwestern University CRS
Chicago, Illinois, 60611
Trinity Health and Wellness Center CRS
Dallas, Texas, 75208
Denver Public Health CRS
Denver, Colorado, 80204
Henry Ford Hosp. CRS
Detroit, Michigan, 48202
Duke University Medical Center CRS
Durham, North Carolina, 27710
Houston AIDS Research Team CRS
Houston, Texas, 77030
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
La Jolla, California, 92093-0672
University of Southern California CRS
Los Angeles, California, 90033-1079
The University of Miami AIDS Clinical Research Unit (ACRU) CRS
Miami, Florida, 33136
Nyu Ny Nichd Crs
New York, New York, 10016
Columbia P&S CRS
New York, New York, 10032-3732
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, 07103
UCSD Antiviral Research Center CRS
San Diego, California, 92103
Ucsf Hiv/Aids Crs
San Francisco, California, 94110
University of Washington AIDS CRS
Seattle, Washington, 98104-9929
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, 10457
Harbor-UCLA CRS
Torrance, California, 90502
Brazil6 sites
Hospital Nossa Senhora da Conceicao CRS
Porto Alegre, Rio Grande do Sul, 91350-200
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, 20221-903
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, 21040-360
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, 26030
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, São Paulo, 14049-900
Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS
São Paulo, 01246-900
Kenya3 sites
Moi University Clinical Research Center (MUCRC) CRS
Eldoret, 30100
Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
Kericho, Rift Valley, 20200
Kisumu Crs
Kisumu, Nyanza, 40100
South Africa3 sites
Durban International Clinical Research Site CRS
Durban, KwaZulu-Natal, 4013
Soweto ACTG CRS
Johannesburg, Gauteng, 1862
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
Johannesburg, Gauteng, 2092
Thailand3 sites
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
Bangkok, 10330
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, 50200
Chonburi Hosp. CRS
Chon Buri, 20000
Haiti2 sites
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, 6110
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port-au-Prince
About this study
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
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.
Read the 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.
- Conditions
- Tuberculosis, HIV Infections
- Being tested
- Rifapentine (RPT), Isoniazid (INH), Pyridoxine (Vitamin B6)
- Medical subject headings
- Tuberculosis, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
Isoniazid (INH)Drug
Participants received one 300-mg tablet or three 100-mg tablets of INH once daily.
Pyridoxine (Vitamin B6)Dietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Isoniazid (INH); Dietary Supplement: Pyridoxine (Vitamin B6) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (9)
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
Measured: 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
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
Measured: 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 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
Measured: From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)
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.
Measured: 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 of Death Due to a Non-TB Event
Cumulative incidence function estimated nonparametrically, treating TB-related deaths as competing risks.
Measured: 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 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.
Measured: After TB diagnosis
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.
Measured: Measured at Weeks 0, 2, 4, and 16
Nevirapine (NVP) Plasma Concentrations in Arm A
Mean and standard deviation
Measured: Measured at Weeks 0, 2, and 4
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.
Measured: Measured at weeks 0, 2 and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2011 (estimated)
- Study start23 May 2012
- Primary completion14 Nov 2017
- Study completion14 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,000 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Richard E. Chaisson, MD, Study chair, Johns Hopkins UniversitySusan Swindells, MBBS, Study chair, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01404312
- Sponsor's protocol ID
- A5279
- Other IDs
- 10848, ACTG A5279
- Status last verified
- Dec 2020
- First submitted
- 26 Jul 2011
- Last updated
- 4 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 19525621Zhang T, Zhang M, Rosenthal IM, Grosset JH, Nuermberger EL. Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1151-7. doi: 10.1164/rccm.200905-0795OC. Epub 2009 Sep 3.
PubMed 19729664Pham MM, Podany AT, Mwelase N, Supparatpinyo K, Mohapi L, Gupta A, Samaneka W, Omoz-Oarhe A, Langat D, Benson CA, Chaisson RE, Swindells S, Fletcher CV. Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing. Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0238521. doi: 10.1128/aac.02385-21. Epub 2022 Aug 9.
PubMed 35943252Haas DW, Podany AT, Bao Y, Swindells S, Chaisson RE, Mwelase N, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Baker P, Fletcher CV. Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine. Pharmacogenet Genomics. 2021 Jan;31(1):17-27. doi: 10.1097/FPC.0000000000000417.
PubMed 32815870Miyahara S, Ramchandani R, Kim S, Evans SR, Gupta A, Swindells S, Chaisson RE, Montepiedra G. Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials. Clin Infect Dis. 2020 Feb 3;70(4):698-703. doi: 10.1093/cid/ciz784.
PubMed 31414121Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.
PubMed 30865794Podany AT, Bao Y, Swindells S, Chaisson RE, Andersen JW, Mwelase T, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Kim P, Fletcher CV; AIDS Clinical Trials Group A5279 Study Team. Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. Clin Infect Dis. 2015 Oct 15;61(8):1322-7. doi: 10.1093/cid/civ464. Epub 2015 Jun 16.
PubMed 26082504
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01404312
- Acronym / sponsor ID
- A5279
- Conditions
- Tuberculosis, HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,000 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 23 May 2012 (actual)
- Primary completion
- 14 Nov 2017 (actual)
- Study completion
- 14 Nov 2017 (actual)
- First posted
- 28 Jul 2011 (estimated)
- Results
- Posted 6 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RPT plus INH Regimen (Arm A) | Experimental | Drug: Rifapentine (RPT), Drug: Isoniazid (INH), Dietary Supplement: Pyridoxine (Vitamin B6)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. |
| INH Regimen (Arm B) | Active comparator | Drug: Isoniazid (INH), Dietary Supplement: Pyridoxine (Vitamin B6)Participants received 300 mg of INH and 25 mg or 50 mg of pyridoxine (vitamin B6) each day during Weeks 1 to 36. |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | RPT plus INH Regimen (Arm A) |
| Isoniazid (INH)Participants received one 300-mg tablet or three 100-mg tablets of INH once daily. | Drug | INH Regimen (Arm B), RPT plus INH Regimen (Arm A) |
| 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. | Dietary supplement | INH Regimen (Arm B), RPT plus INH Regimen (Arm A) |
Primary outcome
Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause
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)
Incidence rate (events per 100 person-years) was estimated, and 95.1% confidence interval used to account for interim analysis of primary efficacy outcome.
9 secondary outcomes
Number of Participants With Occurrence of One or More Serious Adverse Events (SAEs) Versus no SAEs
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)
Number of Participants With a Targeted Adverse Event
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)
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
Time frame: From entry to end of treatment (up to 8 weeks for Arm A; up to 54 weeks for Arm B)
Cumulative Incidence of Death From Any Cause
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)
Cumulative Incidence of Death Due to a Non-TB Event
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)
Number of Participants With Antibiotic Resistance Among Mycobacterium Tuberculosis (MTB) Isolates in Participants Who Develop Active Tuberculosis
Time frame: After TB diagnosis
Efavirenz (EFV) Plasma Concentrations in Arm A
Time frame: Measured at Weeks 0, 2, 4, and 16
Nevirapine (NVP) Plasma Concentrations in Arm A
Time frame: Measured at Weeks 0, 2, and 4
EFV Plasma Concentrations in Arm B
Time frame: Measured at weeks 0, 2 and 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19525621Golub 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.
- Background: PubMed 19729664Zhang T, Zhang M, Rosenthal IM, Grosset JH, Nuermberger EL. Short-course therapy with daily rifapentine in a murine model of latent tuberculosis infection. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1151-7. doi: 10.1164/rccm.200905-0795OC. Epub 2009 Sep 3.
- Derived from this study: PubMed 35943252Pham MM, Podany AT, Mwelase N, Supparatpinyo K, Mohapi L, Gupta A, Samaneka W, Omoz-Oarhe A, Langat D, Benson CA, Chaisson RE, Swindells S, Fletcher CV. Population Pharmacokinetic Modeling and Simulation of Rifapentine Supports Concomitant Antiretroviral Therapy with Efavirenz and Non-Weight Based Dosing. Antimicrob Agents Chemother. 2022 Sep 20;66(9):e0238521. doi: 10.1128/aac.02385-21. Epub 2022 Aug 9.
- Derived from this study: PubMed 32815870Haas DW, Podany AT, Bao Y, Swindells S, Chaisson RE, Mwelase N, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Baker P, Fletcher CV. Pharmacogenetic interactions of rifapentine plus isoniazid with efavirenz or nevirapine. Pharmacogenet Genomics. 2021 Jan;31(1):17-27. doi: 10.1097/FPC.0000000000000417.
- Derived from this study: PubMed 31414121Miyahara S, Ramchandani R, Kim S, Evans SR, Gupta A, Swindells S, Chaisson RE, Montepiedra G. Applying a Risk-benefit Analysis to Outcomes in Tuberculosis Clinical Trials. Clin Infect Dis. 2020 Feb 3;70(4):698-703. doi: 10.1093/cid/ciz784.
- Derived from this study: PubMed 30865794Swindells S, Ramchandani R, Gupta A, Benson CA, Leon-Cruz J, Mwelase N, Jean Juste MA, Lama JR, Valencia J, Omoz-Oarhe A, Supparatpinyo K, Masheto G, Mohapi L, da Silva Escada RO, Mawlana S, Banda P, Severe P, Hakim J, Kanyama C, Langat D, Moran L, Andersen J, Fletcher CV, Nuermberger E, Chaisson RE; BRIEF TB/A5279 Study Team. One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-1011. doi: 10.1056/NEJMoa1806808.
- Derived from this study: PubMed 26082504Podany AT, Bao Y, Swindells S, Chaisson RE, Andersen JW, Mwelase T, Supparatpinyo K, Mohapi L, Gupta A, Benson CA, Kim P, Fletcher CV; AIDS Clinical Trials Group A5279 Study Team. Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention. Clin Infect Dis. 2015 Oct 15;61(8):1322-7. doi: 10.1093/cid/civ464. Epub 2015 Jun 16.
- DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND PEDIATRIC ADVERSE EVENTS VERSION 1.0, DECEMBER, 2004; CLARIFICATION AUGUST 2009Link provided by the sponsor.
- Manual for Expedited Reporting of Adverse Events to DAIDSLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard E. Chaisson, MD study chair
Johns Hopkins University
Susan Swindells, MBBS study chair
University of Nebraska
45 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifapentine (RPT), Isoniazid (INH) and Pyridoxine (Vitamin B6) in people with Tuberculosis and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in United States, Brazil, Kenya, South Africa, Thailand and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of First Diagnosis of Active Tuberculosis, Death Related to Tuberculosis, or Death From Unknown Cause (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01404312, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.