TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment

NCT ID: NCT00140309

Last Updated: 2007-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31
• Study Completion Date: 2005-12-31

Brief Summary

This study is a placebo-controlled factorial study, randomized to study drug (moxifloxacin vs. ethambutol) and treatment frequency (daily vs. thrice weekly after an initial two weeks of daily therapy) during the first two months of standard treatment (with isoniazid, rifampin, and pyrazinamide) for sputum smear-positive pulmonary tuberculosis.

Detailed Description

The primary objective of this Phase II clinical trial is to compare the safety and microbiological activity of a moxifloxacin-containing regimen (isoniazid, rifampin, pyrazinamide, moxifloxacin [HRZMoxi]) to a control regimen (isoniazid, rifampin, pyrazinamide, ethambutol [HRZE]) in the first two months of treatment of sputum smear-positive pulmonary tuberculosis. In addition, the study will evaluate whether intermittent administration (thrice-weekly after the first 2 weeks) of these regimens affects their tolerability and microbiological activity. The assessment of microbiological activity will be sputum culture-conversion. Improved sputum culture conversion after 2 months of treatment with a moxifloxacin-containing regimen would support phase 3 clinical trials of moxifloxacin in treatment regimens of less than the current 6 month standard regimens.

Conditions

Tuberculosis, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

moxifloxacin (with isoniazid, rifampin, pyrazinamide)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Suspected pulmonary tuberculosis with acid-fast bacilli in a stained sputum smear - patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to rifampin will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment.

2. Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment

3. 7 or fewer days of tuberculosis therapy in the 6 months preceding enrollment

4. Age > 18 years

5. Karnofsky score of at least 60

6. Signed informed consent

7. Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual sex.

8. Laboratory parameters within 14 days of enrollment:

• Serum amino aspartate transferase (AST) activity less than 3 times the upper limit of normal
• Serum total bilirubin level less than 2.5 times upper limit of normal
• Serum creatinine level less than 2 times upper limit of normal
• Hemoglobin level of at least 7.0 g/dL
• Platelet count of at least 50,000/mm3
• Serum potassium > 3.0 meq/L
• Negative pregnancy test (for women of childbearing potential)

Exclusion Criteria

1. Breast-feeding

2. Known intolerance to any of the study drugs

3. Known allergy to any fluoroquinolone antibiotic

4. Current or planned therapy during the first 2 months of tuberculosis treatment using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy)

5. Current or planned antiretroviral therapy during the first 2 months of tuberculosis treatment

6. History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, or ziprasidone during the first 2 months of tuberculosis treatment.

7. Pulmonary silicosis

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

Sponsors

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Principal Investigators

William Burman, MD

Role: PRINCIPAL_INVESTIGATOR

Denver Public Health Department

Richard E Chaisson, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

University of Southern California Medical Center

Los Angeles, California, United States

University of California at San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Denver Public Health Department

Denver, Colorado, United States

Washington DC Veterans Administration Medical Center

Washington D.C., District of Columbia, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Hines Vetrans Administration Medical Center

Hines, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

Boston University Medical Center

Boston, Massachusetts, United States

New Jersey School of Medicine

Newark, New Jersey, United States

New York University School of Medicine

New York, New York, United States

Columbia University

New York, New York, United States

Harlem Hospital Center

New York, New York, United States

Veterans Administration Tennessee Valley Health Care System

Nashville, Tennessee, United States

University of North Texas Health Science Center

Fort Worth, Texas, United States

Houston Veterans Administration Medical Center

Houston, Texas, United States

Audie L Murphy Memorial Veterans Administration Medical Center

San Antonio, Texas, United States

Seattle-King County Health Department

Seattle, Washington, United States

University of British Columbia

Vancouver, British Columbia, Canada

University of Manitoba

Winnipeg, Manitoba, Canada

Montreal Chest Institute

Montreal, Quebec, Canada

Nelson R Mandela School of Medicine

Durban, KwaZulu-Natal, South Africa

Makerere University Medical School

Kampala, , Uganda

Countries

United States; Canada; South Africa; Uganda

References

Burman WJ, Goldberg S, Johnson JL, Muzanye G, Engle M, Mosher AW, Choudhri S, Daley CL, Munsiff SS, Zhao Z, Vernon A, Chaisson RE. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med. 2006 Aug 1;174(3):331-8. doi: 10.1164/rccm.200603-360OC. Epub 2006 May 4.

Reference Type: RESULT

PMID: 16675781 (View on PubMed)

Zhang N, Savic RM, Boeree MJ, Peloquin CA, Weiner M, Heinrich N, Bliven-Sizemore E, Phillips PPJ, Hoelscher M, Whitworth W, Morlock G, Posey J, Stout JE, Mac Kenzie W, Aarnoutse R, Dooley KE; Tuberculosis Trials Consortium (TBTC) and Pan African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) Networks. Optimising pyrazinamide for the treatment of tuberculosis. Eur Respir J. 2021 Jul 20;58(1):2002013. doi: 10.1183/13993003.02013-2020. Print 2021 Jul.

Reference Type: DERIVED

PMID: 33542052 (View on PubMed)

Related Links

http://www.cdc.gov/nchstp/tb/tbtc/default.htm

Tuberculosis Trials Consortium (TBTC) web page

Other Identifiers

CDC-NCHSTP-3716

Identifier Type: -

Identifier Source: org_study_id