A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB

Abstract

<b>BACKGROUND:</b> Treatment for TB is lengthy and toxic, and new regimens are needed.<b>METHODS:</b> Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa₂₀₀MZ) or 4 months (4Pa₂₀₀MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa₁₀₀MZ); or standard DS-TB treatment for 6 months. The primary outcome was treatment failure or relapse at 12 months post-randomisation. The non-inferiority margin for between-group differences was 12.0%. Recruitment was paused following three deaths and not resumed.<b>RESULTS:</b> Respectively 4/47 (8.5%), 11/57 (19.3%), 14/52 (26.9%) and 1/53 (1.9%) DS-TB outcomes were unfavourable in patients on 6Pa₂₀₀MZ, 4Pa₂₀₀MZ, 4Pa₁₀₀MZ and controls. There was a 6.6% (95% CI -2.2% to 15.4%) difference per protocol and 9.9% (95%CI -4.1% to 23.9%) modified intention-to-treat difference in unfavourable responses between the control and 6Pa₂₀₀MZ arms. Grade 3+ adverse events affected 68/203 (33.5%) receiving experimental regimens, and 19/68 (27.9%) on control. Ten of 203 (4.9%) participants on experimental arms and 2/68 (2.9%) controls died.<b>CONCLUSION:</b> PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.