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Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis

Information source: Johns Hopkins University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Tuberculosis

Intervention: Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid (Drug); Isoniazid, Rifampin, Pyrazinamide, Ethambutol (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Johns Hopkins University

Official(s) and/or principal investigator(s):
Susan Dorman, MD, Principal Investigator, Affiliation: Johns Hopkins University

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.

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

To compare, by treatment group, the proportions of patients with a negative sputum culture at the end of intensive phase therapy.

To compare the safety and tolerability of the 2 intensive phase regimens.

Secondary outcome:

To compare the time to respiratory culture conversion of the 2 intensive phase regimens, using data from weekly cultures.

To compare, by treatment group, the proportions of subjects who experience treatment failure.

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.

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.

To store serum for future assessment of hypersensitivity to study drugs, should it occur; to store plasma for future assessment of drug concentrations

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Locations and Contacts

Hospital Universitario Clementio Fraga Filho, Rio de Janeiro, Brazil

Posto de Saude Albert Sabin, Rio de Janeiro, RJ 20211-110, Brazil

Centro de Referência Professor Hélio Fraga - ENSP - FIOCRUZ, Curicica, Rio de Janeiro 22.780-192, Brazil

Additional Information

Related publications:

Rosenthal IM, Williams K, Tyagi S, Peloquin CA, Vernon AA, Bishai WR, Grosset JH, Nuermberger EL. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. Epub 2006 Mar 30.

Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med. 2004 Feb 1;169(3):421-6. Epub 2003 Oct 24.

Nuermberger EL, Yoshimatsu T, Tyagi S, Williams K, Rosenthal I, O'Brien RJ, Vernon AA, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med. 2004 Nov 15;170(10):1131-4. Epub 2004 Aug 11.

Starting date: November 2009
Last updated: April 1, 2013

Page last updated: August 23, 2015

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