Overview

This trial is active, not recruiting.

Condition tuberculosis
Treatments rifapentine, moxifloxacin, pyrazinamide, isoniazid, isoniazid, rifampin, pyrazinamide, ethambutol
Phase phase 2
Sponsor Johns Hopkins University
Collaborator Universidade Federal do Rio de Janeiro
Start date November 2009
End date August 2013
Trial size 216 participants
Trial identifier NCT00728507, 06-0018

Summary

Although effective therapy for tuberculosis is available, TB continues to cause significant problems worldwide, and rates of multi-drug resistant (MDR) TB cases are on the rise. A major obstacle to the control of TB is poor adherence with lengthy (usually 6 months) and complicated treatment regimens. Incomplete TB treatment can lead to serious consequences such as increased severity of illness and death, prolonged infectiousness and transmission in the community, and the development of drug resistance. The development of new treatment strategies with more stronger drugs could lead to shorter and simpler regimens. A TB treatment regimen that allowed treatment duration to be meaningfully decreased would have important public health implications.

This trial will compare the effect and safety of a new oral regimen to that of the standard regimen for the first phase of treatment for pulmonary tuberculosis.

The experimental regimen will consist of the following:

- Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.

The standard control intensive phase regimen will consist of the following:

- Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.

Following intensive phase therapy (the study phase), all patients will be treated with a non-experimental continuation phase regimen.

In mice, the combination of Moxifloxacin and Rifapentine have cured the animals significantly faster than the standard regimen and this study will be the first step to see if the potential is also there in humans.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Two months of isoniazid, rifapentine, pyrazinamide and moxifloxacin (HPZM) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
rifapentine, moxifloxacin, pyrazinamide, isoniazid Priftin, Avelox
Rifapentine:150mg tablets, dose = 300mg for subjects <= 45kg and 450mg for those >45kg by mouth once a day for 8 weeks; Moxifloxacin 400mg tablet by mouth once a day for 8 weeks, Isoniazid and Pyrazinamide per standard of care for TB treatment.
(Active Comparator)
Two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) administered once daily. Pyridoxine (vitamin B6) will be given with each dose of isoniazid.
isoniazid, rifampin, pyrazinamide, ethambutol
Administered per standard of care for TB treatment

Primary Outcomes

Measure
To compare, by treatment group, the proportions of patients with a negative sputum culture at the end of intensive phase therapy.
time frame: Week 8
To compare the safety and tolerability of the 2 intensive phase regimens.
time frame: Weekly or more frequent

Secondary Outcomes

Measure
To compare the time to respiratory culture conversion of the 2 intensive phase regimens, using data from weekly cultures.
time frame: Weekly
To compare, by treatment group, the proportions of subjects who experience treatment failure.
time frame: Month 6
To compare, by HIV serostatus, a) the safety of the 2 intensive phase regimens, b) the proportions of patients with negative sputum cultures at the end of intensive phase therapy, and c) the time to culture conversion using data from weekly cultures.
time frame: Weekly or more frequent
To compare, in subjects with versus without cavitation on baseline chest x-ray, the proportions of patients with negative sputum cultures at the end of intensive phase therapy.
time frame: Week 8
To store serum for future assessment of hypersensitivity to study drugs, should it occur; to store plasma for future assessment of drug concentrations
time frame: Future

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Presumptive diagnosis of sputum smear-positive pulmonary TB. - Age: ≥18 years - Seven (7) or fewer days of multidrug therapy for TB disease in the preceding 6 months. - Seven (7) or fewer days of fluoroquinolone therapy in the preceding 3 months. - Documentation of HIV infection status. - For HIV seropositive individuals, a CD4 T lymphocyte count of greater than or equal to 200 cells/mm3. - Documentation of study baseline laboratory parameters done at, or ≤ 14 days prior to screening: - AST less than or equal to 2.5 times upper limit of normal. - Total bilirubin level less than 2.5 times upper limit of normal. - Creatinine level less than 2 times upper limit of normal. - Hemoglobin level of at least 8.0 g/dl. - Platelet count of at least 75,000 mm3. - Potassium level of at least 3.5. - Negative pregnancy test (women of childbearing potential). - Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs). - Male or nonpregnant, nonnursing female. - Provision of informed consent. Exclusion Criteria: - CD4 count < 200 cells/cu mm. - Presence of active AIDS-related opportunistic infection (other than TB) or active AIDS-related malignancy. - Known intolerance to any of the study drugs. - Concomitant disorders or conditions for which any of the study drugs is contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis. - Inability to take oral medication. - Central nervous system TB. - Pulmonary silicosis. - Current or planned therapy, during study phase (intensive phase of TB treatment), with any one or more of the following drugs: quinidine, procainamide, amiodarone, sotalol, disopyramide, terfenadine, cisapride, erythromycin, clarithromycin, phenothiazines, haloperidol, olanzapine, ziprasidone, tricyclic antidepressants, chronic corticosteroids administered either orally or intravenously, chronic fluconazole,chronic itraconazole, chronic ketoconazole, oral or intravenous tacrolimus, oral or intravenous cyclosporine, HIV protease inhibitor, HIV non-nucleoside reverse transcriptase inhibitor. - Concurrent severe and/or uncontrolled medical or psychiatric condition that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol. - Unable or unwilling to receive directly observed therapy and/or adhere with follow-up (e.g. due to residence remote from the study site). - Refusal of consent.

Additional Information

Official title A Phase II Randomized, Open-label Trial of a Rifapentine Plus Moxifloxacin-Based Regimen for Intensive Phase Treatment of Smear-Positive Pulmonary Tuberculosis
Principal investigator Susan Dorman, MD
Trial information was received from ClinicalTrials.gov and was last updated in April 2013.
Information provided to ClinicalTrials.gov by Johns Hopkins University.