New treatments 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 might have additive activity to existing antituberculosis agents. We assessed
the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment.
We undertook a phase II, double-blind, randomised controlled trial of a regimen that
included moxifloxacin in adults with sputum smear-positive tuberculosis at one hospital
in Rio de Janeiro, Brazil. 170 participants received isoniazid, rifampicin, and pyrazinamide
at standard doses and were assigned by permuted block randomisation to receive either
moxifloxacin (400 mg) with an ethambutol placebo (n=85) or ethambutol (15-20 mg/kg)
plus moxifloxacin placebo (n=85) 5 days per week for 8 weeks. The primary endpoint
was the proportion of patients whose sputum culture had converted to negative by week
8. Analysis was by modified intention to treat (ITT); patients whose baseline cultures
were negative, contaminated, or contained drug-resistant Mycobacterium tuberculosis
were excluded from the analysis. Additionally, all missing 8-week results were deemed
treatment failures. This study is registered with ClinicalTrials.gov, number NCT00082173.
74 patients assigned to the moxifloxacin group and 72 in the ethambutol group were
included in the modified ITT population. 125 patients had 8-week data (moxifloxacin
n=64, ethambutol n=61); the main reason for absence of data was culture contamination.
At 8 weeks, culture conversion to negative had occurred in 59 (80%) of 74 patients
in the moxifloxacin group compared with 45 (63%) of 72 in the ethambutol group (difference
17.2%, 95% CI 2.8-31.7; p=0.03). There were 16 adverse events (eight in each group)
in 12 patients. Only one event was judged related to study drug (grade 3 cutaneous
reaction in the ethambutol group).
Moxifloxacin improved culture conversion in the initial phase of tuberculosis treatment.
Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis
treatment are justified.