Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis

NCT ID: NCT00728507

Last Updated: 2017-04-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2013-04-30

Brief 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.

Conditions

Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

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

Group Type: EXPERIMENTAL

Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid

Intervention Type: DRUG

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.

2

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

Group Type: ACTIVE_COMPARATOR

Isoniazid, Rifampin, Pyrazinamide, Ethambutol

Intervention Type: DRUG

Administered per standard of care for TB treatment

Interventions

Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid

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.

Intervention Type: DRUG

Isoniazid, Rifampin, Pyrazinamide, Ethambutol

Administered per standard of care for TB treatment

Intervention Type: DRUG

Other Intervention Names

Priftin, Avelox

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade Federal do Rio de Janeiro

OTHER

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Dorman, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Centro de Referência Professor Hélio Fraga - ENSP - FIOCRUZ

Curicica, Rio de Janeiro, Brazil

Posto de Saude Albert Sabin

Rio de Janeiro, Rio de Janeiro, Brazil

Hospital Universitario Clementio Fraga Filho

Rio de Janeiro, , Brazil

Countries

Brazil

References

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. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.

Reference Type: BACKGROUND

PMID: 16574936 (View on PubMed)

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. doi: 10.1164/rccm.200310-1380OC. Epub 2003 Oct 24.

Reference Type: BACKGROUND

PMID: 14578218 (View on PubMed)

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. doi: 10.1164/rccm.200407-885OC. Epub 2004 Aug 11.

Reference Type: BACKGROUND

PMID: 15306535 (View on PubMed)

Conde MB, Mello FC, Duarte RS, Cavalcante SC, Rolla V, Dalcolmo M, Loredo C, Durovni B, Armstrong DT, Efron A, Barnes GL, Marzinke MA, Savic RM, Dooley KE, Cohn S, Moulton LH, Chaisson RE, Dorman SE. A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis. PLoS One. 2016 May 9;11(5):e0154778. doi: 10.1371/journal.pone.0154778. eCollection 2016.

Reference Type: DERIVED

PMID: 27159505 (View on PubMed)

Other Identifiers

06-0018

Identifier Type: -

Identifier Source: org_study_id