TBTC Study 28: Moxifloxacin Versus Isoniazid for TB Treatment

• Status: Completed
• Trial end date: 2007-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This double-blind, randomized controlled trial evaluates moxifloxacin versus isoniazid in daily treatment during the first two months of treatment with rifampin, pyrazinamide and ethambutol for sputum smear-positive pulmonary tuberculosis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centers for Disease Control and Prevention
• Collaborators: Bayer; Global Alliance for TB Drug Development
• Treatments: Ethambutol; Fluoroquinolones; Isoniazid; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination; Pyrazinamide; Rifampin

Criteria

Inclusion Criteria:

• Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum. Patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to (one or more) isoniazid, rifampin, fluoroquinolones, 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. Sputum must be expectorated or induced; smear results from respiratory secretions obtained by bronchoalveolar lavage or bronchial wash may not be used for assessment of study eligibility.

• 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. HIV testing does not need to be repeated if there is written documentation of a positive test (positive ELISA and Western Blot or a plasma HIV-RNA level greater than 5000 copies/ml) at any time in the past.

• 7 (seven) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment.

• 7 (seven) or fewer days of fluoroquinolone therapy in the 3 months preceding enrollment.

• Age > 18 years

• Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B).

• Signed informed consent

• Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.

• Laboratory parameters done at, or <14 days prior to, screening:

• Serum amino aspartate transferase (AST) activity ≤ 3 times the upper limit of normal

• Serum total bilirubin level ≤ 2.5 times the upper limit of normal

• Serum creatinine level ≤ 2 times the upper limit of normal

• Complete blood count with hemoglobin level of at least 7.0 g/dL

• Complete blood count with platelet count of at least 50,000/mm3

• Serum potassium > 3.5 meq/L

• Negative pregnancy test (women of childbearing potential)

Exclusion Criteria:

• Breast-feeding

• Known intolerance to any of the study drugs

• Known allergy to any fluoroquinolone antibiotic

• Concomitant disorders or conditions for which moxifloxacin (MXF), isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.

• Current or planned therapy during the intensive phase of therapy using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy).

• Current or planned antiretroviral therapy during the intensive phase of therapy.

• History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine during the intensive phase of therapy.

• Pulmonary silicosis

• Central nervous system TB