NCT00144417

TBTC Study 28: Moxifloxacin Versus Isoniazid for TB Treatment

TBTC Study 28: Evaluation of a Moxifloxacin-based, Isoniazid-sparing Regimen for Tuberculosis Treatment

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 433 (actual)
• Sponsor: Centers for Disease Control and Prevention · Federal
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The primary objective of this Phase 2 clinical trial is to compare the safety and antimicrobial activity of a moxifloxacin-containing regimen (moxifloxacin, rifampin, pyrazinamide, ethambutol \[MRZE\]) in which moxifloxacin has been substituted for isoniazid, to the standard control regimen (isoniazid, rifampin, pyrazinamide, ethambutol \[HRZE\]) in the first two months of treatment of sputum smear-positive pulmonary tuberculosis. The assessment of antimicrobial activity will be sputum culture-conversion. Higher rates of 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. Rationale - Current treatment of smear positive pulmonary tuberculosis requires a minimum of 6 months, a treatment duration that is challenging for patients and tuberculosis control programs. Therefore, a high priority in tuberculosis research is the identification of agents that can shorten treatment. Several fluoroquinolone antibiotics have potent activity against Mycobacterium tuberculosis (M. tuberculosis) in preclinical testing. Of the currently available fluoroquinolones, moxifloxacin has excellent activity in vitro and in animal models of tuberculosis, a favorable pharmacokinetic profile (serum half-life of 10-12 hours), lack of problematic drug-drug interactions, no need for dosage adjustment for renal and hepatic insufficiency, and an excellent safety profile. In addition, in the murine model of tuberculosis, the substitution of moxifloxacin for isoniazid resulted in significant reductions in the time to culture conversion and the time to sterilization when compared to the standard combination rifampin, isoniazid and pyrazinamide. However, moxifloxacin has not been fully evaluated in humans for tuberculosis treatment. There is a need to assess not only the anti-tuberculosis activity of moxifloxacin-containing regimens, but also the safety of more prolonged therapy with moxifloxacin. Two-month culture conversion rates are a well-accepted surrogate marker for the sterilizing activity of anti-tuberculosis drugs. Rifampin and pyrazinamide, the key drugs in current 6-month regimens, markedly increase 2-month culture-conversion rates. Therefore, this study will use 2-month culture conversion rate as the measure of antimicrobial activity of moxifloxacin.

Conditions

• Tuberculosis

Interventions

Type	Name	Description
DRUG	Moxifloxacin (with rifampin, pyrazinamide, and ethambutol)	Moxifloxacin 400mg daily, 8 weeks
DRUG	isoniazid	isoniazid, oral, 300 mg, daily, 8 weeks

Timeline

• Start date: 2006-02-01
• Primary completion: 2007-06-01
• Completion: 2007-12-01
• First posted: 2005-09-05
• Last updated: 2011-08-03

Locations

26 sites across 6 countries: United States, Brazil, Canada, South Africa, Spain, Uganda