TBTC Study 29: Rifapentine During Intensive Phase Tuberculosis (TB) Treatment

NCT00694629 | Completed Phase 2 Results DMC

• 1 other identifier: CDC-NCHSTP-5399
• Study Type: interventional
• Target: 334
• Locations: 6 countries
• Sites: 29

Brief Summary

This Phase 2, multicenter, open-label clinical trial evaluated the antimicrobial activity and safety of rifapentine-containing regimens during the intensive phase of pulmonary tuberculosis treatment. Participants were randomized to receive either a standard rifampin-based regimen (RHZE) or a rifapentine-substituted regimen (PHZE). An extension study evaluated higher daily doses of rifapentine (10, 15, and 20 mg/kg). The primary endpoint was sputum culture conversion at 8 weeks. Secondary outcomes included time to culture conversion, safety, and treatment discontinuation.

Conditions

Pulmonary Tuberculosis

Keywords

pulmonary tuberculosis; treatment

Outcome Measures

Primary Outcomes (2)

• Participants With Negative Sputum Culture at 8 Weeks

  Proportion of participants with negative Mycobacterium tuberculosis sputum cultures at completion of the 8-week intensive phase of treatment.

  8 weeks.

• Participants Who Discontinued Treatment During Intensive Phase

  Number of participants who permanently discontinued assigned study treatment for any reason during the first 8 weeks.

  8 weeks

Study Arms (4)

Standard TB Treatment (RHZE): Rifampin 10 mg/kg Daily for 8 Weeks

ACTIVE COMPARATOR

rifampin, isoniazid, pyrazinamide, ethambutol

Drug: rifapentine

Rifapentine 10 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

EXPERIMENTAL

rifapentine 10 mg/kg, isoniazid, pyrazinamide, ethambutol

Drug: rifapentine 10 mg/kg

Rifapentine 15 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

EXPERIMENTAL

rifapentine 15 mg/kg, isoniazid, pyrazinamide, ethambutol

Drug: rifapentine 15 mg/kg

Rifapentine 20 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

EXPERIMENTAL

rifapentine 20 mg/kg, isoniazid, pyrazinamide, ethambutol

Drug: rifapentine 20 mg/kg

Interventions

rifapentine DRUG

tablet, 10 mg/kg, daily, 8 weeks

Also known as: Rifadin

Standard TB Treatment (RHZE): Rifampin 10 mg/kg Daily for 8 Weeks

rifapentine 15 mg/kg DRUG

tablet, 15 mg/kg, daily, 8 weeks

Also known as: Priftin

Rifapentine 15 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

rifapentine 10 mg/kg DRUG

tablet, 10 mg/kg, daily, 8 weeks

Also known as: Priftin

Rifapentine 10 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

rifapentine 20 mg/kg DRUG

20 mg/kg, daily, 8 weeks

Also known as: Priftin

Rifapentine 20 mg/kg Daily TB Treatment (PHZE) for 8 Weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum.
• Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 3 months prior to enrollment.
• (five) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding initiation of study drugs.
• (seven) or fewer days of fluoroquinolone therapy in the 30 days preceding initiation of study drugs.
• Age \>= 18 years
• Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B)
• Signed informed consent
• Women of child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
• Laboratory parameters done within 14 days prior to, enrollment:
• Serum or plasma alanine aminotransferase (ALT) activity ≤ 3 times the upper limit of normal
• Serum or plasma total bilirubin level ≤ 2.5 times the upper limit of normal
• Serum or plasma creatinine level ≤ 2 times the upper limit of normal
• Complete blood count with hemoglobin level of at least 7.0 g/dL
• Complete blood count with platelet count of at least 100,000/mm3
• Negative pregnancy test (women of childbearing potential)

You may not qualify if:

• Pregnant or breast-feeding
• Known intolerance or allergy to any of the study drugs
• Concomitant disorders or conditions for which isoniazid (INH), rifamycins, pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
• Current or planned therapy, during the intensive phase of TB therapy, with combination antiretroviral therapy for HIV, or with cyclosporine or tacrolimus. Cyclosporine and tacrolimus have unacceptable interactions with rifamycins.
• Pulmonary silicosis
• Central nervous system TB
• Weight \< 40 kg or \> 85 kg

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Sanofi: collaborator

Study Sites (29)

Central Arkansas Veterans Health System

Little Rock, Arkansas, 72205, United States

Location

LA County/USC Medical Center

Los Angeles, California, 90033, United States

Location

University of Southern California Medical Center

Los Angeles, California, 90033, United States

Location

University of California at San Diego

San Diego, California, 92103, United States

Location

University of California, San Francincisco

San Francisco, California, 94110, United States

Location

Denver Department of Public Health and Hospitals

Denver, Colorado, 80204, United States

Location

Washington DC Veterans Administration Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30303, United States

Location

Chicago VA Medical Center (Lakeside)

Chicago, Illinois, 60611, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Hines VA Medical Center

Hines, Illinois, 60141, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21231, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

New Jersey Medical School

Newark, New Jersey, 07107-3001, United States

Location

Columbia University/Presbyterian Medical Center

New York, New York, 10032, United States

Location

Harlem Hospital, Columbia University

New York, New York, 10037, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Nashville VA Medical Center

Nashville, Tennessee, 37212-2637, United States

Location

Veterans Administration Tennessee Valley Health Care System

Nashville, Tennessee, 37232, United States

Location

University of North Texas Health Science Center

Fort Worth, Texas, 76104, United States

Location

Houston Veterans Administration Medical Center

Houston, Texas, 77030, United States

Location

Audi L. Murphy VA Hospital

San Antonio, Texas, 78284, United States

Location

Seattle King County Health Department

Seattle, Washington, 98104, United States

Location

Hopital Universitario Clementino Fraga Filho

Rio de Janeiro, 2194.590, Brazil

Location

University of Manitoba

Winnepeg, Manitoba, R3A 1R8, Canada

Location

Montreal Chest Institute McGill University

Montreal, Quebec, H2X 2P4Pq Canada, Canada

Location

Nelson R Mandela School of Medicine

Durban, KwaZulu-Natal, South Africa

Location

Agencia de Salut Publica

Barcelona, 08023, Spain

Location

Makerere University Medical School

Kampala, Uganda

Location

Related Publications (5)

• Dorman SE, Goldberg S, Stout JE, Muzanyi G, Johnson JL, Weiner M, Bozeman L, Heilig CM, Feng PJ, Moro R, Narita M, Nahid P, Ray S, Bates E, Haile B, Nuermberger EL, Vernon A, Schluger NW; Tuberculosis Trials Consortium. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the tuberculosis trials consortium. J Infect Dis. 2012 Oct 1;206(7):1030-40. doi: 10.1093/infdis/jis461. Epub 2012 Jul 30.

  PMID: 22850121 RESULT

• Gewitz AD, Solans BP, Mac Kenzie WR, Heilig C, Whitworth WC, Johnson JL, Nsubuga P, Dorman S, Weiner M, Savic RM; Tuberculosis Trials Consortium of the Centers for Disease Control and Prevention. Longitudinal Model-Based Biomarker Analysis of Exposure-Response Relationships in Adults with Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0179420. doi: 10.1128/AAC.01794-20. Epub 2021 Jul 12.

  PMID: 34252302 DERIVED

• Jarsberg LG, Kedia K, Wendler J, Wright AT, Piehowski PD, Gritsenko MA, Shi T, Lewinsohn DM, Sigal GB, Weiner MH, Smith RD, Keane J, Jacobs JM, Nahid P. Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region. PLoS One. 2021 May 5;16(5):e0250586. doi: 10.1371/journal.pone.0250586. eCollection 2021.

  PMID: 33951066 DERIVED

• Weiner M, Gelfond J, Johnson-Pais TL, Engle M, Johnson JL, Whitworth WC, Bliven-Sizemore E, Nsubuga P, Dorman SE, Savic R; Pharmacokinetics/Pharmacodynamics Group of Tuberculosis Trials Consortium. Decreased plasma rifapentine concentrations associated with AADAC single nucleotide polymorphism in adults with tuberculosis. J Antimicrob Chemother. 2021 Feb 11;76(3):582-586. doi: 10.1093/jac/dkaa490.

  PMID: 33374006 DERIVED

• Dorman SE, Savic RM, Goldberg S, Stout JE, Schluger N, Muzanyi G, Johnson JL, Nahid P, Hecker EJ, Heilig CM, Bozeman L, Feng PJ, Moro RN, MacKenzie W, Dooley KE, Nuermberger EL, Vernon A, Weiner M; Tuberculosis Trials Consortium. Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial. Am J Respir Crit Care Med. 2015 Feb 1;191(3):333-43. doi: 10.1164/rccm.201410-1843OC.

  PMID: 25489785 DERIVED

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

rifapentine; Rifampin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Susan Dorman, MD
• Organization: Johns Hopkins University

clinicaltrials@cdc.gov

1-800-CDC-INFO

Study Officials

• Susan Dorman, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Neil Schluger, MD

  Columbia University

  STUDY CHAIR

• Jason Stout, MD

  Duke University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2008
• First Posted: June 10, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: December 1, 2013
• Last Updated: July 23, 2026
• Results First Posted: July 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1); ES (1); US (23); ZA (1); CA (2); UG (1)