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

C. D. Tweed, G. H. Wills, A. M. Crook, E. Amukoye, V. Balanag, A. Y.L. Ban, A. L.C. Bateson, M. C. Betteridge, W. Brumskine, J. Caoili, R. E. Chaisson, M. Cevik, F. Conradie, R. Dawson, A. del Parigi, A. Diacon, D. E. Everitt, S. M. Fabiane, R. Hunt, A. I. IsmailU. Lalloo, L. Lombard, C. Louw, M. Malahleha, T. D. McHugh, C. M. Mendel, F. Mhimbira, R. N. Moodliar, V. Nduba, A. J. Nunn, I. Sabi, M. A. Sebe, R. A.P. Selepe, S. Staples, S. Swindells, C. H. van Niekerk, E. Variava, M. Spigelman, S. H. Gillespie

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalInternational Journal of Tuberculosis and Lung Disease
Volume25
Issue number4
DOIs
StatePublished - Apr 1 2021

Keywords

  • Drug resistance
  • K E Y W O R D S: tuberculosis
  • TB treatment
  • TB-HIV

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Fingerprint Dive into the research topics of 'A partially randomised trial of pretomanid, moxifloxacin and pyrazinamide for pulmonary TB'. Together they form a unique fingerprint.

Cite this