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

• Published in: International Journal of Tuberculosis and Lung Disease
• Main Author: Tweed C.D.; Wills G.H.; Crook A.M.; Amukoye E.; Balanag V.; Ban A.Y.L.; Bateson A.L.C.; Betteridge M.C.; Brumskine W.; Caoili J.; Chaisson R.E.; Cevik M.; Conradie F.; Dawson R.; del Parigi A.; Diacon A.; Everitt D.E.; Fabiane S.M.; Hunt R.; Ismail A.I.; Lalloo U.; Lombard L.; Louw C.; Malahleha M.; McHugh T.D.; Mendel C.M.; Mhimbira F.; Moodliar R.N.; Nduba V.; Nunn A.J.; Sabi I.; Sebe M.A.; Selepe R.A.P.; Staples S.; Swindells S.; van Niekerk C.H.; Variava E.; Spigelman M.; Gillespie S.H.
• Format: Article
• Language: English
• Published: International Union Against Tuberculosis and Lung Disease 2021
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85103500407&doi=10.5588%2fIJTLD.20.0513&partnerID=40&md5=8c765dc0d897b2fc30f93aff84366e37

B A C K G R O U N D: Treatment for TB is lengthy and toxic, and new regimens are needed. M E T H O D S: 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. R E S U LT S: 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 6Pa2 0 0MZ, 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 3þ 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. C O N C L U S I O N: PaMZ regimens did not achieve non-inferiority in this under-powered trial. An ongoing evaluation of PMD remains a priority. © 2021 International Union against Tubercul. and Lung Dis.. All rights reserved.