QT effects of bedaquiline, delamanid or both in patients with rifampicin-resistant-TB: a randomized controlled trial
Abstract
SUMMARY Background: Bedaquiline and delamanid are the first drugs of new classes registered for tuberculosis treatment in 40 years. Each can prolong the QTc interval, with maximum effects weeks after drug initiation. The cardiac safety and microbiologic activity of these drugs when co-administered is not well-established. Methods: ACTG A5343 is a phase 2, open-label trial in which adults with multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) receiving multidrug background treatment were randomized 1:1:1 using centrally, computer-generated randomization, using permuted blocks to receive bedaquiline, delamanid, or both for 24 weeks. Individuals with QTc >450ms were excluded. HIV-positive participants received dolutegravir-based ART. Clofazimine was disallowed, and levofloxacin replaced moxifloxacin. Triplicate ECG and sputum cultures were performed fortnightly. The primary endpoint was mean QTcF change from baseline (averaged over weeks 8–24). Findings: 84 participants (28 in each treatment group, and 31 in total with HIV) were enrolled in South Africa and Peru. Mean (95% CI) change (ms) in QTc from baseline was 12.3 (7.8, 16.7) (bedaquiline), 8.6 (4.0, 13.1) (delamanid), and 20.7 (16.1, 25.3) (bedaquiline+delamanid). There were no Grade 3 or 4 QTc prolongation events and no deaths during study treatment. Cumulative culture conversion by Week 8 was 88% (21/24, bedaquiline), 83% (20/24 delamanid), and 95% (19/20, bedaquiline+delamanid) and was 92%, 91%, and 95%,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 84 participants or records.
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