Study of Daily Rifapentine for Pulmonary Tuberculosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Cape Town Lung Institute
University of Cape Town
Information provided by (Responsible Party):
Susan E. Dorman, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00814671
First received: December 24, 2008
Last updated: June 3, 2014
Last verified: June 2014
  Purpose

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 TB.

Funding Source- FDA OOPD


Condition Intervention Phase
Tuberculosis
Drug: Rifapentine
Drug: Rifampin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • To estimate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg based on proportion of participants with culture conversion [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To estimate the frequency of side effects of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment, based on time to sputum culture conversion [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To evaluate the microbiological activity of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment, based on time to culture growth in MGIT liquid media [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To describe the pharmacokinetics of rifapentine administered at once daily doses of 450 mg and 600 mg in the context of multidrug intensive phase TB treatment [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • To determine if rifapentine exposures are associated with microbiological activity [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • To determine if rifapentine exposures are associated with safety [ Time Frame: 10 weeks ] [ Designated as safety issue: Yes ]
  • To compare Lowenstein Jensen and Bactec MGIT media with respect to proportion of participants with 8-week culture conversion and time to culture conversion [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 153
Study Start Date: April 2010
Estimated Study Completion Date: July 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RPT450
Rifapentine 450mg daily
Drug: Rifapentine
rifapentine 450 mg + isoniazid + pyrazinamide + ethambutol once a day, seven days a week for 8 weeks
Other Name: Priftin
Drug: Rifapentine
rifapentine 600 mg + isoniazid + pyrazinamide + ethambutol once a day, seven days a week for 8 weeks
Other Name: Priftin
Active Comparator: RIF 600
Rifampin 600mg daily
Drug: Rifampin
rifampin 600 mg + isoniazid + pyrazinamide + ethambutol once a day, seven days a week for 8 weeks
Other Name: Rifampacin
Experimental: RPT 600
Rifapentine 600mg daily
Drug: Rifapentine
rifapentine 450 mg + isoniazid + pyrazinamide + ethambutol once a day, seven days a week for 8 weeks
Other Name: Priftin
Drug: Rifapentine
rifapentine 600 mg + isoniazid + pyrazinamide + ethambutol once a day, seven days a week for 8 weeks
Other Name: Priftin

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814671

Locations
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
Investigators
Principal Investigator: Susan Dorman, MD Johns Hopkins University
  More Information

Publications:
Responsible Party: Susan E. Dorman, Associate Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00814671     History of Changes
Other Study ID Numbers: 3524
Study First Received: December 24, 2008
Last Updated: June 3, 2014
Health Authority: United States: Food and Drug Administration
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council

Keywords provided by Johns Hopkins University:
Tuberculosis
Pharmacokinetics

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Rifampin
Rifapentine
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014