A Partially Randomised Trial Of Pretomanid, Moxifloxacin And Pyrazinamide For Pulmonary Tb

BACKGROUND: Treatment for TB is lengthy and toxic, and new regimens are needed.METHODS : Participants with pulmonary drug-susceptible TB (DS-TB) were randomised to receive: 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500mg pyrazinamide (Z) for 6 months (6Pa(200)MZ) or 4 months (4Pa(200)MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa(100)MZ); 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.RESULTS : 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 6Pa(200)MZ, 4Pa(200)MZ, 4Pa(100)MZ 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 6Pa(200)MZ arms. Grade 3thorn 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.CONCLUSION: PaMZ regimens did not achieve noninferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority.