TB-PRACTECAL (NCT02589782) is a two-stage, multi-arm, randomised, controlled, open label phase II/III clinical trial evaluating the safety and efficacy of three 24-week all-oral regimens for the treatment of rifampicin resistant tuberculosis. We present results comprising all three investigational arms.
Adults and children above 15 years were enrolled into the trial from six sites in Uzbekistan, Belarus and South Africa. Participants were randomised to receive one of three investigational regimens or the control. BPaL arm consisted of bedaquiline 400mg daily for 2 weeks then 200mg three times a week for 22 weeks, pretomanid 200mg daily for 24 weeks and tapered dose linezolid 600mg daily for 16 weeks then 300mg for 8 weeks. Clofazimine 100mg daily for 24 weeks was added in BPaLC arm or Moxifloxacin 400mg daily for 24 weeks in BPaLM arm. All participants were planned for follow up to 108 weeks post randomisation. The primary outcome was the percentage of patients with a composite unfavourable outcome (treatment failure, death, treatment discontinuation, recurrence, loss to follow-up) at 72 weeks post-randomisation. The non-inferiority margin was 12%.
Enrolment started in January 2017 and was terminated early for benefit in March 2021. 152 (37%, 27%), 123 (47%, 33%), 126 (33%, 26%) and 151 (44%, 25%) participants (% female, % HIV) were randomised to the Control, BPaL, BPaLC and BPaLM arms respectively. In the modified intention to treat population, the percentage of unfavourable outcomes were 48.5% for the Control, 23.3% for BPaL, 18.8% for BPaLC and 11.3% for BPaLM (see figure 1 for details). There were three recurrencies in BPaL, one in BPaLC and none in BPaLM. Secondary analyses at 24, 48 and 108 weeks post-randomisation were consistent with the primary outcomes. One participant died in BPaLC arm, two in the Control and none in BPaLM and BPaL arms. Participants experiencing at least one grade ?3 and/or serious adverse event were 58.9%, 21.7%, 31.9%,19.4% in the Control, BPaL, BPaLC and BPaLM respectively. The mean QTcF prolongation from baseline at 24 weeks was 44.9ms, 23.3ms, 40.2ms and 27.0ms for the Control, BPaL, BPaLC and BPaLM arms respectively.
24 week all oral regimens containing a backbone of bedaquiline, pretomanid and tapered dose linezolid are both safe and efficacious in the treatment of rifampicin resistant tuberculosis.