A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis.

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.).

• Authors: Bern-Thomas Nyang'wa, Catherine Berry, Emil Kazounis, Ilaria Motta, Nargiza Parpieva, Zinaida Tigay, Varvara Solodovnikova, Irina Liverko, Ronelle Moodliar, Matthew Dodd, Nosipho Ngubane, Mohammed Rassool, Timothy D McHugh, Melvin Spigelman, David A J Moore, Koert Ritmeijer, Philipp du Cros, Katherine Fielding, TB-PRACTECAL Study Collaborators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 387 Issue 25 Pg. 2331-2343 (12 22 2022) ISSN: 1533-4406 [Electronic] United States
• PMID: 36546625 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Massachusetts Medical Society.

Chemical References

• Antitubercular Agents
• Moxifloxacin
• Rifampin
• bedaquiline
• pretomanid
• Linezolid

Topics

• Humans
• Antitubercular Agents (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Drug Therapy, Combination
• Moxifloxacin (administration & dosage, adverse effects, therapeutic use)
• Rifampin (adverse effects, pharmacology)
• Tuberculosis, Multidrug-Resistant (drug therapy)
• Tuberculosis, Pulmonary (drug therapy)
• Adolescent
• Young Adult
• Adult
• Linezolid (administration & dosage, adverse effects, therapeutic use)
• Administration, Oral