Brief Rifapentine-Isoniazid Evaluation for TB Prevention (BRIEF TB)
NCT ID: NCT01404312
Last Updated: 2021-11-04
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE3
3000 participants
INTERVENTIONAL
2012-05-23
2017-11-14
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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 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)
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 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.
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 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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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).
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 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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
* 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
13 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Richard E. Chaisson, MD
Role: STUDY_CHAIR
Johns Hopkins University
Susan Swindells, MBBS
Role: STUDY_CHAIR
University of Nebraska
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of California, UC San Diego CRS- Mother-Child-Adolescent HIV Program
La Jolla, California, United States
University of Southern California CRS
Los Angeles, California, United States
UCSD Antiviral Research Center CRS
San Diego, California, United States
Ucsf Hiv/Aids Crs
San Francisco, California, United States
Harbor-UCLA CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Denver Public Health CRS
Denver, Colorado, United States
The University of Miami AIDS Clinical Research Unit (ACRU) CRS
Miami, Florida, United States
Northwestern University CRS
Chicago, Illinois, United States
Boston Medical Center CRS
Boston, Massachusetts, United States
Henry Ford Hosp. CRS
Detroit, Michigan, United States
Cooper Univ. Hosp. CRS
Camden, New Jersey, United States
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States
Nyu Ny Nichd Crs
New York, New York, United States
Columbia P&S CRS
New York, New York, United States
Bronx-Lebanon Hospital Center NICHD CRS
The Bronx, New York, United States
Chapel Hill CRS
Chapel Hill, North Carolina, United States
Duke University Medical Center CRS
Durham, North Carolina, United States
Trinity Health and Wellness Center CRS
Dallas, Texas, United States
Houston AIDS Research Team CRS
Houston, Texas, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Gaborone CRS
Gaborone, , Botswana
Molepolole CRS
Gaborone, , Botswana
Hospital Nossa Senhora da Conceicao CRS
Porto Alegre, Rio Grande do Sul, Brazil
Univ. of Sao Paulo Brazil NICHD CRS
São Paulo, São Paulo, Brazil
Hospital Federal dos Servidores do Estado NICHD CRS
Rio de Janeiro, , Brazil
Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS
Rio de Janeiro, , Brazil
Hosp. Geral De Nova Igaucu Brazil NICHD CRS
Rio de Janeiro, , Brazil
Inst de Infectologia Emilio Ribas Sao Paulo Brazil NICHD CRS
São Paulo, , Brazil
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
Port-au-Prince, , Haiti
GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS
Port-au-Prince, , Haiti
Kisumu Crs
Kisumu, Nyanza, Kenya
Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS
Kericho, Rift Valley, Kenya
Moi University Clinical Research Center (MUCRC) CRS
Eldoret, , Kenya
Malawi CRS
Lilongwe, Central Region, Malawi
Blantyre CRS
Blantyre, , Malawi
Barranco CRS
Lima, , Peru
San Miguel CRS
Lima, , Peru
Soweto ACTG CRS
Johannesburg, Gauteng, South Africa
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
Johannesburg, Gauteng, South Africa
Durban International Clinical Research Site CRS
Durban, KwaZulu-Natal, South Africa
Thai Red Cross AIDS Research Centre (TRC-ARC) CRS
Bangkok, , Thailand
Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS
Chiang Mai, , Thailand
Chonburi Hosp. CRS
Chon Buri, , Thailand
Parirenyatwa CRS
Harare, , Zimbabwe
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
Zhang 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.
Pham 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.
Haas 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.
Miyahara 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.
Swindells 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.
Podany 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.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
Access external resources that provide additional context or updates about the study.
DIVISION OF AIDS TABLE FOR GRADING THE SEVERITY OF ADULT AND PEDIATRIC ADVERSE EVENTS VERSION 1.0, DECEMBER, 2004; CLARIFICATION AUGUST 2009
Manual for Expedited Reporting of Adverse Events to DAIDS
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
10848
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG A5279
Identifier Type: OTHER
Identifier Source: secondary_id
A5279
Identifier Type: -
Identifier Source: org_study_id