TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment
TBTC Study 27: Moxifloxacin vs Ethambutol for TB Treatment
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.
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.
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