Nunn AJ, et al. – In this trial, researchers validated findings from cohort studies in Bangladesh conferring promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. Participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides were included in this phase 3 noninferiority trial. In these patients, the short regimen was non-inferior with respect to the primary efficacy and had similar safety when compared to a long regimen.

Methods

• Participants were randomized in a 2:1 ratio to receive either a short regimen (9-11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines.
• The main efficacy outcome was favorable status at 132, based on Mycobacterium tuberculosis-negative cultures at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome.
• They determined noninferiority using an upper 95% confidence limit for the between-group difference in favorable status that was ≤ 10 percentage points.

Results

• Researchers randomized 424 participants; approximately 90% comprised the modified intention-to-treat population.
• In the long-regimen group and the short-regimen group, 79.8% and 78.8% of the participants, respectively, reported attainment of favorable status—a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% CI: −7.5 to 9.5; P=0.02 for noninferiority).
• They attained consistent results with respect to noninferiority among the 321 participants in the per-protocol population (adjusted difference, –0.7 percentage points; 95% CI, −10.5 to 9.1).
• Grade 3 or higher adverse events were reported in 45.4% and 48.2% of the participants in the long-regimen group and the short-regimen group, respectively.
• Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia’s formula) to 500 msec occurred in 11.0% of participants and 6.4% of the participants in the short-regimen group and the long-regimen group, respectively (P=0.14); because of the greater incidence, participants in the short-regimen group were closely monitored and some received medication adjustments.
• Death was reported for 8.5% of participants in the short-regimen group and 6.4% in the long-regimen group; acquired resistance to fluoroquinolones or aminoglycosides was reported in 3.3% and 2.3%, respectively.