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TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment

Phase 2
Completed
Conditions
Tuberculosis, Pulmonary
Registration Number
NCT00140309
Lead Sponsor
Centers for Disease Control and Prevention
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
350
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Primary Outcome Measures
NameTimeMethod
Two-month culture conversion
Serious Adverse Event
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (23)

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 DC, 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

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University of Southern California Medical Center
🇺🇸Los Angeles, California, United States

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