Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial

Abstract

Background New therapies are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that may have additive activity to existing antituberculosis agents. We conducted a Phase 2 clinical trial to determine the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment. Methods We performed a randomized, double-blind trial of a moxifloxacin-containing regimen in patients with sputum smear-positive tuberculosis in Brazil. All participants received isoniazid, rifampin and pyrazinamide at standard doses and were randomized to receive either moxifloxacin or ethambutol and matching placebos five days per week for eight weeks. The primary endpoint was the proportion of patients whose sputum culture converted to negative by Week 8. Clinical trial identifier: NCT00082173. Results One hundred seventy patients were enrolled, and 146 met all study eligibility criteria. In an intention to treat analysis where missing results were considered treatment failures, 59 patients (80%) assigned to moxifloxacin converted their 8-week sputum culture to negative vs. 45 (63%) of those assigned to ethambutol (p=0.03). Among patients with available cultures at Week 8, conversion rates were 92% (59/64) for moxifloxacin vs. 72% (45/61) for ethambutol (p=0.006). No differences in toxicity were observed. In a multivariate analysis, younger age (odds ratio 0.98, p=0.05), heavy baseline sputum smear positivity (OR 0.45, p <0.001) and treatment with moxifloxacin (OR 1.88, p<0.001) were significantly associated with sputum culture conversion. Conclusion Moxifloxacin significantly improves culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis therapy are justified.