Back to results

Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis

Primary Purpose

Tuberculosis

Status

Terminated

Phase

Phase 2

Locations

Brazil

Study Type

Interventional

Intervention

Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid

Isoniazid, Rifampin, Pyrazinamide, Ethambutol

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Tuberculosis, Moxifloxacin, Rifapentine

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Centro de Referência Professor Hélio Fraga - ENSP - FIOCRUZ
Posto de Saude Albert Sabin
Hospital Universitario Clementio Fraga Filho

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

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

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

Outcomes

Primary Outcome Measures

To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.

LJ culture conversion

To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.

Study was prematurely terminated and data was not collected for this outcome measure.

Secondary Outcome Measures

Full Information

NCT ID

NCT00728507

First Posted

July 30, 2008

Last Updated

March 8, 2017

Sponsor

Johns Hopkins University

Collaborators

Universidade Federal do Rio de Janeiro

1. Study Identification

Unique Protocol Identification Number

NCT00728507

Brief Title

Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis

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 Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Terminated

Why Stopped

Funding withdrawn

Study Start Date

November 2009 (undefined)

Primary Completion Date

April 2013 (Actual)

Study Completion Date

April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

Universidade Federal do Rio de Janeiro

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Tuberculosis, Moxifloxacin, Rifapentine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

121 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

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

Arm Title

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Rifapentine, Moxifloxacin, Pyrazinamide, Isoniazid

Other Intervention Name(s)

Priftin, Avelox

Intervention Description

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

Intervention Name(s)

Isoniazid, Rifampin, Pyrazinamide, Ethambutol

Intervention Description

Administered per standard of care for TB treatment

Primary Outcome Measure Information:

Title

To Compare, by Treatment Group, the Percentage of Patients With a Negative Sputum Culture at the End of Intensive Phase Therapy.

Description

LJ culture conversion

Time Frame

Week 8

Title

To Compare the Safety and Tolerability of the 2 Intensive Phase Regimens.

Description

Study was prematurely terminated and data was not collected for this outcome measure.

Time Frame

Weekly or more frequent

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

100 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susan Dorman, MD

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centro de Referência Professor Hélio Fraga - ENSP - FIOCRUZ

City

Curicica

State/Province

Rio de Janeiro

ZIP/Postal Code

22.780-192

Country

Brazil

Facility Name

Posto de Saude Albert Sabin

City

Rio de Janeiro

State/Province

ZIP/Postal Code

20211-110

Country

Brazil

Facility Name

Hospital Universitario Clementio Fraga Filho

City

Rio de Janeiro

Country

Brazil

12. IPD Sharing Statement

Citations:

PubMed Identifier

16574936

Citation

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.

Results Reference

background

PubMed Identifier

14578218

Citation

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.

Results Reference

background

PubMed Identifier

15306535

Citation

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.

Results Reference

background

PubMed Identifier

27159505

Citation

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.

Results Reference

derived

Learn more about this trial

Rifapentine Plus Moxifloxacin for Treatment of Pulmonary Tuberculosis

We'll reach out to this number within 24 hrs