The Frequency and Incidence of QT Prolongation With Extended Use of Bedaquiline or Delamanid in a Large, Multi-Country Multidrug-Resistant/ Rifampicin-Resistant Tuberculosis Cohort

Khan U. Rich M. Franke M.F. Lachenal N. Ahmed S. Bekele A. Isani A.K. Hewison C. Sari C.Y.I. Tan C.L. Varaine F. Flores E.H. Putri F.A. Faqirzai J. Beauchamp J. Vo L.N.Q. Siddiqui M.R. Seung K. Bastard M. Nkunkanyirazo P. Kiria N. Khan M. Algozhin Y. Melikyan N. Saki N.A. Vilbrun S.C. Fatima R. Naing Y.Y. Islam S. Mamsa S. Mitnick C.D. Huerga H. Khan P.Y.
15 July 2025 Oxford University Press

Clinical Infectious Diseases
2025 #81 Issue 1 153 - 158 pp.

Background. The 2022 World Health Organization (WHO) guidelines on multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) recommend 6 months of bedaquiline (Bdq) in the all-oral 9-month shorter regimen and 6 months or longer for Bdq and delamanid (Dlm) in the 18–20-month longer regimen. However, lack of evidence on extended treatment using Bdq or Dlm has limited their use to 6 months. We examine the frequency and incidence of QT prolongation based on duration of Bdq and/or Dlm use in longer regimens. Methods. We analyzed a prospective cohort of MDR/RR-TB patients from 16 countries who initiated treatment with Bdq and/ or Dlm containing regimens from 1 April 2015 to 30 September 2018. Data were systematically collected using a shared protocol. The outcome of interest was the first clinically relevant prolonged QT interval (grade 3 or above) or a serious adverse event (SAE) involving prolonged QT of any grade. Results. Among 2553 patients, 59% received >6 months of Bdq and/or Dlm. Of these, 579 (20.9%) patients experienced a prolonged QT event, the majority (95.5%) being grade 1 or 2. Sixty-four (2.5%) patients experienced the outcome of interest with only 12 (0.5%) having ≥1 QT prolonging drugs permanently suspended. The incidence rate of the first prolonged QT event was highest in the first six months of treatment and lower in subsequent 6-month periods. Conclusions. We demonstrate that Bdq and/or Dlm use beyond 6 months is safe in longer MDR/RR-TB regimens with most clinically relevant QT prolongation events occurring in the first 6 months. Electrocardiogram (ECG) monitoring for early identification of QT prolongating events is possible in programmatic conditions.

adverse events , bedaquiline , delamanid , extended use , QT prolongation

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Interactive Research & Development (IRD) Global, Singapore, Singapore
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
Division of Global Health Equity, Brigham and Women’s Hospital, Boston, MA, United States
Partners In Health, Boston, MA, United States
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, United States
Pharmacovigilance Unit, Médecins Sans Frontières, Geneva, Switzerland
Interactive Research & Development (IRD), Karachi, Pakistan
Addis Ababa University College of Health Sciences, Addis Ababa, Ethiopia
Communicable Disease Control (CDC), Directorate General Health Services, Sindh, Pakistan
Medical Department, Médecins Sans Frontières, Paris, France
RS Islam Jakarta Cempaka Putih, Jakarta, Indonesia
Médecins Sans Frontières, Minsk, Belarus
Arzobispo Loayza Hospital, Lima, Peru
Interactive Research & Development (IRD), Jakarta, Indonesia
Médecins Sans Frontières, Yerevan, Armenia
Zanmi Lasante, Cange, Haiti
Friends for International TB Relief, Hanoi, Viet Nam
Department of Global Public Health, WHO Collaboration Centre on Tuberculosis and Social Medicine, Karolinska Institute, Stockholm, Sweden
Institute of Chest Diseases (ICD) Kotri, Sindh, Pakistan
Field Epidemiology Department, Epicentre, Paris, France
Partners In Health, Lesotho, Maseru, Lesotho
Médecins Sans Frontières, Tbilisi, Georgia
Interactive Research & Development (IRD), Durban, South Africa
Partners In Health, Almaty, Kazakhstan
National TB Programme, Dhaka, Bangladesh
GHESKIO Institute of Infectious Diseases and Reproductive Health, NTP, Port-au-Prince, Haiti
National TB Control Program, Common Management Unit (HIV, TB, Malaria), Islamabad, Pakistan
Médecins Sans Frontières, Yangon, Myanmar
Interactive Research & Development (IRD), Dhaka, Bangladesh
Indus Hospital and Health Network (IHHN), Karachi, Pakistan
Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom

Interactive Research & Development (IRD) Global
Department of Epidemiology
Division of Global Health Equity
Partners In Health
Department of Global Health and Social Medicine
Pharmacovigilance Unit
Interactive Research & Development (IRD)
Addis Ababa University College of Health Sciences
Communicable Disease Control (CDC)
Medical Department
RS Islam Jakarta Cempaka Putih
Médecins Sans Frontières
Arzobispo Loayza Hospital
Interactive Research & Development (IRD)
Médecins Sans Frontières
Zanmi Lasante
Friends for International TB Relief
Department of Global Public Health
Institute of Chest Diseases (ICD) Kotri
Field Epidemiology Department
Partners In Health
Médecins Sans Frontières
Interactive Research & Development (IRD)
Partners In Health
National TB Programme
GHESKIO Institute of Infectious Diseases and Reproductive Health
National TB Control Program
Médecins Sans Frontières
Interactive Research & Development (IRD)
Indus Hospital and Health Network (IHHN)
Clinical Research Department

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