Journal Article

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

McHugh, Timothy D., Kazounis, Emil, Dodd, Matthew, Parpieva, Nargiza, Moore, David A.J., Motta, Ilaria, du Cros, Philipp, Berry, Catherine, Ngubane, Nosipho, Moodliar, Ronelle, Spigelman, Melvin, Fielding, Katherine, Solodovnikova, Varvara, Nyang’wa, Bern-Thomas, Ritmeijer, Koert, Tigay, Zinaida, Rassool, Mohammed, Liverko, Irina

2022

Overview

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. 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. 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%). 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.).

• Publisher: Massachusetts Medical Society
• Subject: Administration, Oral / Adolescent / Adult / Adverse events / Antibiotics / Antitubercular Agents - administration & dosage / Antitubercular Agents - adverse effects / Antitubercular Agents - pharmacology / Antitubercular Agents - therapeutic use / Clinical trials / Drug dosages / Drug Therapy, Combination / Global Health / Humans / Infectious Disease / Infectious Disease General / Laboratories / Linezolid / Linezolid - administration & dosage / Linezolid - adverse effects / Linezolid - therapeutic use / Moxifloxacin / Moxifloxacin - administration & dosage / Moxifloxacin - adverse effects / Moxifloxacin - therapeutic use / Rifampin / Rifampin - adverse effects / Rifampin - pharmacology / Statistical analysis / Tuberculosis / Tuberculosis, Multidrug-Resistant - drug therapy / Tuberculosis, Pulmonary - drug therapy / Young Adult