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

• Main Authors: Amukoye, E. (Author), Balanag, V. (Author), Ban, A.Y.L (Author), Bateson, A.L.C (Author), Betteridge, M.C (Author), Brumskine, W. (Author), Caoili, J. (Author), Cevik, M. (Author), Chaisson, R.E (Author), Conradie, F. (Author), Crook, A.M (Author), Dawson, R. (Author), del Parigi, A. (Author), Diacon, A. (Author), Everitt, D.E (Author), Fabiane, S.M (Author), Gillespie, S.H (Author), Hunt, R. (Author), Ismail, A.I (Author), Lalloo, U. (Author), Lombard, L. (Author), Louw, C. (Author), Malahleha, M. (Author), McHugh, T.D (Author), Mendel, C.M (Author), Mhimbira, F. (Author), Moodliar, R.N (Author), Nduba, V. (Author), Nunn, A.J (Author), Sabi, I. (Author), Sebe, M.A (Author), Selepe, R.A.P (Author), Spigelman, M. (Author), Staples, S. (Author), Swindells, S. (Author), Tweed, C.D (Author), van Niekerk, C.H (Author), Variava, E. (Author), Wills, G.H (Author)
• Format: Article
• Language: English
• Published: International Union Against Tuberculosis and Lung Disease 2021
• Series: International Journal of Tuberculosis and Lung Disease
• Subjects: adult; aged; alanine aminotransferase; Antitubercular Agents; arthralgia; Article; aspartate aminotransferase; clinical protocol; combination drug therapy; controlled study; drug efficacy; Drug resistance; Drug Therapy, Combination; drug withdrawal; ethambutol; female; human; Humans; hypertransaminasemia; hyperuricemia; intention to treat analysis; isoniazid; K E Y W O R D S: tuberculosis; lung tuberculosis; major clinical study; male; moxifloxacin; Moxifloxacin; multicenter study; nitroimidazole derivative; Nitroimidazoles; open study; outcome assessment; patient selection; phase 3 clinical trial; pretomanid; pyrazinamide; Pyrazinamide; randomized controlled trial; relapse; rifampicin; TB treatment; TB-HIV; thorax radiography; treatment duration; treatment failure; treatment outcome; Treatment Outcome; treatment response; tuberculostatic agent
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 10273719 (ISSN)
• DOI: 10.5588/IJTLD.20.0513

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.