Mycobacterial disease · Shortening drug-susceptible TB treatment
Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis
| Design | Randomised, double-blind, placebo-controlled non-inferiority trial |
|---|---|
| Treatment | Four-month regimen with moxifloxacin replacing ethambutol (the trial's 'isoniazid group'), or moxifloxacin replacing isoniazid (its 'ethambutol group') |
| Control | Standard six-month regimen |
| Population | 1931 patients with drug-sensitive pulmonary tuberculosis |
| Follow-up | 18 months |
| Primary endpoint | Favourable outcome, defined as culture-negative status at 18 months without relapse |
| Result | In the per-protocol analysis a favourable outcome occurred in 85% of the group that kept isoniazid and replaced ethambutol, and 80% of the group that kept ethambutol and replaced isoniazid, versus 92% of controls — differences favouring control of 6.1 percentage points (97.5% CI 1.7 to 10.5) and 11.4 points (6.7 to 16.1). Both moxifloxacin regimens produced faster initial culture conversion. Grade 3 or 4 adverse events did not differ: 127 (19%), 111 (17%) and 123 (19%) respectively. |
| Secondary endpoints | Time to culture negativity, relapse rate, adverse events |
The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting.
The trial authors, in the published abstract
The clearest demonstration in tuberculosis that early bactericidal activity does not predict cure. Faster culture conversion, more relapse. It is why Study 31/A5349 succeeded only by adding rifapentine, and why surrogate endpoints in tuberculosis are treated with such suspicion.
Gillespie SH, Crook AM, McHugh TD, et al. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med 2014 Oct 23;371(17):1577-87.