Delamanid was safe and tolerable during a 6-month treatment period in patients with multidrug-resistant tuberculosis (TB). Despite its favorable safety and tolerability profile, the drug did not significantly reduce the median time to sputum culture conversion. Findings from this phase 3 trial were published in Lancet Respiratory Medicine.
Adults with pulmonary multidrug-resistant TB were enrolled at 17 sites across 7 countries. In combination with an optimized background regimen, patients were randomly assigned to either 100 mg twice-daily oral delamanid for 2 months followed by 200 mg once-daily delamanid for 4 months (n=224) or placebo (n=101). Patients were stratified based on risk category for delayed sputum culture conversion. Time to sputum culture conversion during a 6-month treatment period was the primary outcome.
No difference was found between the delamanid and placebo groups in terms of the median time to sputum culture conversion (51 days [interquartile range, 29-98 days] vs 57 days [interquartile range, 43-85 days], respectively; hazard ratio, 1.17; 95% CI, 0.91-1.51; P =.2157). The majority of patients (98.0%) experienced ≥1 treatment-emergent adverse event (TEAE), whereas 26.6% of patients had ≥1 serious TEAE.
There was no difference between the delamanid and placebo groups for the incidence of TEAEs (26.1% vs 27.6%, respectively). Mortality attributable to TEAEs was also similar in patients randomly assigned to either treatment or control (4.4% vs 3.5%, respectively). No deaths were related to the study drug.
The relatively short rate of follow-up, as well as the inclusion of a possibly effective background regimen, may have limited the trial’s findings.
“Further research is needed to understand the role of delamanid in the treatment of [multidrug-resistant] tuberculosis (ie, within both conventional and shorter regimens), with the ultimate goal being to identify simple, safer, patient-centric treatment,” the researchers wrote.
von Groote-Bidlingmaier F, Patientia R, Sanchez E, et al. Efficacy and safety of delamanid in combination with an optimised background regimen for treatment of multidrug-resistant tuberculosis: a multicentre, randomised, double-blind, placebo-controlled, parallel group phase 3 trial [published online January 7, 2019]. Lancet Respir Med. doi:10.1016/S2213-2600(18)30426-0