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Study of Daily Rifapentine for Pulmonary Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00814671
Recruitment Status : Completed
First Posted : December 25, 2008
Results First Posted : September 28, 2016
Last Update Posted : February 6, 2018
University of Cape Town Lung Institute
University of Cape Town
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

The goal of this Phase 2 study is to determine the microbiological activity and safety of rifapentine when given as a component of multidrug intensive phase treatment of smear-positive pulmonary tuberculosis (TB).

Funding Source- FDA Office of Orphan Products Development (OOPD)

Condition or disease Intervention/treatment Phase
Tuberculosis Drug: Rifapentine 450 Drug: Rifapentine 600 Drug: Rifampin Phase 2

Detailed Description:

Prospective phase II, open-label, single center study in which each experimental rifapentine regimen is evaluated using a two-stage design. Adults (HIV-negative, or HIV-positive with CD4 > 200 cells/cu mm) suspected to have pulmonary tuberculosis who meet eligibility criteria will be randomized to receive one of three intensive phase regimens. Intensive phase regimens will consist of once daily isoniazid, pyrazinamide, and ethambutol, plus one of the following: rifampin 600 mg once daily OR rifapentine 450 mg once daily OR rifapentine 600 mg once daily. Randomization will be stratified by presence/absence of cavitation on baseline chest radiograph. In Stage 1, 15 subjects will be randomized to each arm, following which there will be an enrollment pause for efficacy and safety assessment. Any rifapentine regimen for which fewer than 6 of 11 evaluable participants have week 8 culture conversion will be discarded.

Stage 2 will randomize subjects into the remaining "accepted arms" with a maximum of 36 additional subjects per arm.

All subjects will continue TB treatment with a conventional continuation phase treatment.

Study Site

Study subjects will be recruited from the University of Cape Town inpatient wards and outpatient clinics.

Estimated Study Duration

It is estimated that 18 months will be required for recruitment and enrollment of study subjects. The estimated duration of participation for each study subject is 18 months, including 2 months of experimental intensive phase TB treatment, 4 months of non-experimental conventional continuation phase TB treatment, and an additional 12 months for follow-up for TB relapse.

Study Management

Study subjects will have study visits on days 0, 7, 14, 21, 28, 35, 42, 49, and 56 for sputum collection and adverse event assessment. Safety laboratory monitoring will be performed on days 14, 28, 42, and 56 and will consist of complete blood count, serum alanine aminotransferase, serum total bilirubin, and serum creatinine. Steady state pharmacokinetic analysis will be performed on approximately day 28. Subjects will have additional study visits at week 10 and at months 4, 6, 12, and 18.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Open-label Trial of Daily Rifapentine 450mg or 600mg in Place of Rifampicin 600mg for Intensive Phase Treatment of Smear-positive Pulmonary Tuberculosis
Study Start Date : April 2010
Actual Primary Completion Date : June 2013
Actual Study Completion Date : September 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: RPT450
Rifapentine 450mg daily
Drug: Rifapentine 450
rifapentine 450 mg
Other Name: Priftin

Active Comparator: RIF 600
Rifampin 600mg daily
Drug: Rifampin
rifampin 600 mg
Other Name: Rifampacin

Experimental: RPT 600
Rifapentine 600mg daily
Drug: Rifapentine 600
rifapentine 600 mg
Other Name: Priftin

Primary Outcome Measures :
  1. Percentage of Participants With Negative Lowenstein Jensen Cultures at Week 8 [ Time Frame: 8 weeks ]
  2. Tolerability [ Time Frame: 10 weeks ]
    percentage of participants discontinuing assigned treatment

Secondary Outcome Measures :
  1. Time to Stable Culture Conversion on Solid Medium [ Time Frame: 12 weeks ]
    Time to stable culture conversion (in days) on Lowenstein Jensen solid medium

  2. Time to Stable Culture Conversion on Liquid MGIT Media [ Time Frame: 12 weeks ]
    Time (in days) to stable culture conversion on liquid MGIT media

  3. Pharmacokinetics of Rifapentine [ Time Frame: 8 weeks ]
    area under the concentration time curve (AUC[0-24]) for rifapentine administered once daily at doses of 450 mg or 600 mg in the context of multi drug intensive phase TB treatment

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated sputum. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment.
  2. No prior history of tuberculosis disease or tuberculosis treatment
  3. No treatment with fluoroquinolones in the 2 months preceding initiation of study drugs.
  4. Age > 18 years
  5. Weight ≥ 50 kg and ≤ 80 kg
  6. Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix)
  7. Signed informed consent
  8. Ability to adhere with study follow-up
  9. Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
  10. HIV negative, or HIV-positive with CD4 > 200 cells/cu mm
  11. Laboratory parameters done at, or 14 days prior to, screening (with results available for review by study personnel):

    • Serum alanine aminotransferase (ALT) activity ≤ 2 times the upper limit of normal
    • Serum total bilirubin level ≤ 2 times the upper limit of normal
    • Serum creatinine level less than or equal to the upper limit of normal
    • Hemoglobin level of at least 7.0 g/dL
    • Platelet count of at least 100,000/mm3
    • Negative pregnancy test (women of childbearing potential)

Exclusion Criteria:

  1. Pregnant or breast-feeding
  2. Known intolerance or allergy to any of the study drugs
  3. 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.
  4. Current or planned therapy, during the intensive phase of TB therapy with cyclosporine or tacrolimus, or HIV antiretroviral (ARV) therapy, which have unacceptable interactions with rifamycins.
  5. Any medical or psychosocial condition, which, in the view of the study investigator, makes study participation inadvisable.
  6. Pulmonary silicosis
  7. Central nervous system TB

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00814671

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South Africa
Universiy of Cape Town Lung Institute
Cape Town, Western Cape, South Africa, 7937
Sponsors and Collaborators
Johns Hopkins University
University of Cape Town Lung Institute
University of Cape Town
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Principal Investigator: Susan Dorman, MD Johns Hopkins University
Publications of Results:
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Responsible Party: Johns Hopkins University Identifier: NCT00814671    
Other Study ID Numbers: NA_00019095
First Posted: December 25, 2008    Key Record Dates
Results First Posted: September 28, 2016
Last Update Posted: February 6, 2018
Last Verified: January 2018
Keywords provided by Johns Hopkins University:
Additional relevant MeSH terms:
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Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers