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.).
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Background: Around 500 000 people worldwide develop rifampicin-resistant tuberculosis each year. The proportion of successful treatment outcomes remains low and new treatments are needed. Following an interim analysis, we report the final safety and efficacy outcomes of the TB-PRACTECAL trial, evaluating the safety and efficacy of oral regimens for the treatment of rifampicin-resistant tuberculosis.
View Article and Find Full Text PDFA 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis.
N Engl J Med
December 2022
From the Public Health Department, Operational Center Amsterdam (OCA), Médecins sans Frontières, Amsterdam (B.-T.N., K.R.); the Public Health Department, OCA, Médecins sans Frontières (C.B., E.K., I.M.), the London School of Hygiene and Tropical Medicine (B.-T.N., M.D., D.A.J.M., K.F.), and University College London (T.D.M.) - all in London; the Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent (N.P., I.L.), and the Republican Phthisiological Hospital No. 2, Nukus (Z.T.) - both in Uzbekistan; the Republican Scientific and Practical Center for Pulmonology and Tuberculosis, Minsk, Belarus (V.S.); THINK TB and HIV Investigative Network, Durban (R.M.), and Wits Health Consortium, Johannesburg (N.N., M.R.) - both in South Africa; the Global Alliance for TB Drug Development, New York (M.S.); and the Burnet Institute, Melbourne, VIC, Australia (P.C.).
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.
Short article: Retreatment of chronic hepatitis C virus infection after unsuccessful therapy with all-oral direct-acting antiviral regimens: a real-life experience.
Eur J Gastroenterol Hepatol
November 2017
aDepartment of Biomedical and Clinical Sciences L. Sacco, University of Milan bFirst Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, Milan cDepartment of Experimental Medicine and Surgery, University of Rome 'Tor Vergata', Rome, Italy.
Objective: Few real-life data are available on the retreatment of patients who failed direct-acting antiviral (DAA)-regimens. We reported the outcome of retreatment with approved DAA regimens in a real-life cohort of patients who previously failed an all-oral DAAs combination and we analyzed the association with resistance substitutions (RASs) performed at the time of virological failure.
Aim And Methods: Next-generation sequencing of the NS3, NS5A, and NS5B regions was performed by Illumina deep sequencing.
Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure.
Hepatology
December 2017
Service d'Hépatologie, Hôpital Saint-Antoine, Université Pierre & Marie Curie, Paris, France.
Unlabelled: People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies.
View Article and Find Full Text PDFEfficacy and safety outcomes of sofosbuvir-based treatment regimens for hepatitis C virus-infected patients with or without cirrhosis from phase III clinical trials.
Ther Clin Risk Manag
April 2017
Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, South Korea.
Background: With the appearance of oral direct-acting antivirals (DAAs), the field of hepatitis C virus (HCV) treatment has been dramatically changed. This evolution makes possible for all oral treatments to be available for the treatment of HCV-infected patients. The aims of this review were to report the efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of patients with chronic HCV infection and to provide our clinical perspectives on these regimens.
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