TBTC Study 29: Rifapentine During Intensive Phase Tuberculosis (TB) Treatment - Full Text View

Sponsors and Collaborators:	Centers for Disease Control and Prevention Sanofi-Aventis
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00694629

Purpose

Protocol Synopsis The goal of this Phase 2 clinical trial is to evaluate the antimicrobial activity and safety of an experimental intensive phase (first 8 weeks of treatment) tuberculosis treatment regimen in which rifapentine is substituted for rifampin.

Primary Objective

To compare the antimicrobial activity and safety of standard daily regimen comprised of rifampin (approximately 10 mg/kg/dose) + isoniazid + pyrazinamide + ethambutol (RHZE) to that of an experimental regimen comprised of rifapentine (approximately 10 mg/kg/dose) + isoniazid + pyrazinamide + ethambutol (PHZE).

Secondary Objectives

To determine and compare for each regimen the time to culture-conversion, using data from 2-, 4-, 6-, and 8-week cultures (10, 20, 30, 40 doses).
To determine and compare for each regimen the proportion of patients with any Grade 3 or 4 adverse reactions
To determine the correlation of the MGIT/BACTEC liquid culture growth index and other mycobacterial and clinical biomarkers with time to culture conversion and treatment failure
To store serum for future assessment of biomarkers of TB treatment response and hypersensitivity to study drugs.
To compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients

Design

This will be a prospective, multicenter, open-label clinical study. Adults suspected of having pulmonary tuberculosis who meet eligibility criteria will be randomized to receive either the experimental intensive phase tuberculosis treatment regimen or the standard intensive phase tuberculosis treatment regimen. Randomization will be stratified by presence/absence of cavitation on baseline chest radiograph, and by geographic continent. All doses of study drugs will be given under direct observation and administered 5 days per week. After a subject completes intensive phase therapy, he/she then will be treated with a non-experimental continuation phase tuberculosis treatment regimen.

Subjects will have blood drawn for one pharmacokinetic determination of rifapentine concentration towards the end of intensive phase therapy.

Condition	Intervention	Phase
Pulmonary Tuberculosis	Drug: rifampin Drug: rifapentine	Phase II

MedlinePlus related topics: AIDS Tuberculosis

Drug Information available for: Rifampin Rifapentine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	TBTC Study 29: Evaluation of a Rifapentine-Containing Regimen for Intensive Phase Treatment of Pulmonary Tuberculosis

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

The proportion of patients, by regimen, having negative sputum cultures at completion of eight weeks (40 doses) of treatment [ Time Frame: completion of eight weeks (40 doses) of treatment ] [ Designated as safety issue: No ]
The proportion of patients, by regimen, who permanently discontinue the assigned study treatment for any reason during the first eight weeks [ Time Frame: during the first eight weeks of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

time to culture-conversion [ Time Frame: 2-, 4-, 6-, and 8-week cultures (10, 20, 30, 40 doses) ] [ Designated as safety issue: No ]
proportion of patients with any Grade 3 or 4 adverse reactions [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
correlation of the MGIT/BACTEC liquid culture growth index and other mycobacterial and clinical biomarkers with time to culture conversion and treatment failure [ Time Frame: duration of TB treatment ] [ Designated as safety issue: No ]
compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	480
Study Start Date:	December 2008
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator rifampin, isoniazid, pyrazinamide, ethambutol	Drug: rifampin tablet, 10 mg/kg, daily, 8 weeks
2: Experimental rifapentine, isoniazid, pyrazinamide, ethambutol	Drug: rifapentine tablet, 10 mg/kg, daily, 8 weeks

Eligibility

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

Criteria

Inclusion Criteria:

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.
5 (five) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding initiation of study drugs.
7 (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)

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694629

Show 29 Study Locations

Sponsors and Collaborators

Centers for Disease Control and Prevention

Sanofi-Aventis

Investigators

Principal Investigator:	Susan Dorman, MD	Johns Hopkins University
Study Chair:	Neil Schluger, MD	Columbia University
Study Chair:	Jason Stout, MD	Duke University

More Information

Responsible Party:	CDC ( Stefan Goldberg )
Study ID Numbers:	TBTC Study 29
Study First Received:	June 6, 2008
Last Updated:	December 10, 2008
ClinicalTrials.gov Identifier:	NCT00694629
Health Authority:	United States: Food and Drug Administration

Keywords provided by Centers for Disease Control and Prevention:

pulmonary tuberculosis
treatment

Study placed in the following topic categories:

Bacterial Infections
Rifampin
Gram-Positive Bacterial Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Tuberculosis, pulmonary

Lung Diseases
Tuberculosis, Pulmonary
Rifapentine
Mycobacterium Infections
Tuberculosis

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-Bacterial Agents
Therapeutic Uses
Antitubercular Agents

Pharmacologic Actions
Actinomycetales Infections
Leprostatic Agents
Antibiotics, Antitubercular

ClinicalTrials.gov processed this record on January 16, 2009