Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis - PubMed (original) (raw)

Randomized Controlled Trial

. 2009 Aug 1;180(3):273-80.

doi: 10.1164/rccm.200901-0078OC. Epub 2009 Apr 30.

John L Johnson, Stefan Goldberg, Grace Muzanye, Nesri Padayatchi, Lorna Bozeman, Charles M Heilig, John Bernardo, Shurjeel Choudhri, Jacques H Grosset, Elizabeth Guy, Priya Guyadeen, Maria Corazon Leus, Gina Maltas, Dick Menzies, Eric L Nuermberger, Margarita Villarino, Andrew Vernon, Richard E Chaisson; Tuberculosis Trials Consortium

Collaborators, Affiliations

Randomized Controlled Trial

Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis

Susan E Dorman et al. Am J Respir Crit Care Med. 2009.

Abstract

Rationale: Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited.

Objectives: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB.

Methods: Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment.

Measurements and main results: Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25).

Conclusions: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.

Trial registration: ClinicalTrials.gov NCT00144417.

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