Nyang'wa, Bern-Thomas; Berry, Catherine; Kazounis, Emil; Motta, Ilaria; Parpieva, Nargiza; Tigay, Zinaida; Solodovnikova, Varvara; Liverko, Irina; Moodliar, Ronelle; Dodd, Matthew; +9 more... Ngubane, Nosipho; Rassool, Mohammed; McHugh, Timothy D; Spigelman, Melvin; Moore, David AJ; Ritmeijer, Koert; du Cros, Philipp; Fielding, Katherine; TB-PRACTECAL Study Collaborators; (2022) A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. New England Journal of Medicine, 387 (25). pp. 2331-2343. ISSN 0028-4793 DOI: https://doi.org/10.1056/NEJMoa2117166
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Abstract
BACKGROUND: In patients with rifampin-resistant tuberculosis, all-oral treatment regimens that are more effective, shorter, and have a more acceptable side-effect profile than current regimens are needed. METHODS: We conducted an open-label, phase 2-3, multicenter, randomized, controlled, noninferiority trial to evaluate the efficacy and safety of three 24-week, all-oral regimens for the treatment of rifampin-resistant tuberculosis. Patients in Belarus, South Africa, and Uzbekistan who were 15 years of age or older and had rifampin-resistant pulmonary tuberculosis were enrolled. In stage 2 of the trial, a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen. The primary outcome was an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization. The noninferiority margin was 12 percentage points. RESULTS: Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively. In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard-care group had a primary-outcome event (risk difference, -37 percentage points; 96.6% confidence interval [CI], -53 to -22). In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard-care group had a primary-outcome event (risk difference, -9 percentage points; 96.6% CI, -22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%). CONCLUSIONS: In patients with rifampin-resistant pulmonary tuberculosis, a 24-week, all-oral regimen was noninferior to the accepted standard-care treatment, and it had a better safety profile. (Funded by Médecins sans Frontières; TB-PRACTECAL ClinicalTrials.gov number, NCT02589782.).
Item Type | Article |
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Faculty and Department |
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research Faculty of Epidemiology and Population Health > Dept of Medical Statistics Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology & International Health (2023-) |
Research Centre | TB Centre |
PubMed ID | 36546625 |
Elements ID | 197486 |
Official URL | http://dx.doi.org/10.1056/nejmoa2117166 |