{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:43:53Z","timestamp":1790045033743,"version":"4.0.1"},"reference-count":23,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"M\u00e9decins Sans Fronti\u00e8res"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,7,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Regimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A\n              <jats:italic>post hoc<\/jats:italic>\n              analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF &gt;450 ms (of 3,744) and only one QTcF &gt;500 ms. The odds of QTcF &gt;450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25\u201321.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CLINICAL TRIALS<\/jats:title>\n            <jats:p>\n              This study is registered with\n              <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"pre-results\" document-id=\"NCT02589782\" document-id-type=\"clinical-trial-number\" source-id=\"http:\/\/clinicaltrials.gov\/\" source-id-type=\"registry-nameov\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/show\/NCT02589782\">\n                <jats:ext-link ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link>\n                as\n                <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02589782\" xlink:type=\"simple\">NCT02589782<\/jats:ext-link>\n              <\/jats:related-object>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00536-24","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T13:00:19Z","timestamp":1717678819000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["How much should we still worry about QTc prolongation in rifampicin-resistant tuberculosis? ECG findings from TB-PRACTECAL clinical trial"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-3192","authenticated-orcid":true,"given":"Ilaria","family":"Motta","sequence":"first","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-2314","authenticated-orcid":true,"given":"Martina","family":"Cusinato","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene &amp; Tropical Medicine (LSHTM), London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-4295","authenticated-orcid":true,"given":"Andrew J.","family":"Ludman","sequence":"additional","affiliation":[{"name":"Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Lachenal","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-6604","authenticated-orcid":true,"given":"Matthew","family":"Dodd","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene &amp; Tropical Medicine (LSHTM), London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2527-592X","authenticated-orcid":true,"given":"Moe","family":"Soe","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tleubergen","family":"Abdrasuliev","sequence":"additional","affiliation":[{"name":"Republican Phthisiological Hospital, Nukus, Karakalpakstan, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruzilya","family":"Usmanova","sequence":"additional","affiliation":[{"name":"Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9498-1085","authenticated-orcid":true,"given":"Ilhomjon","family":"Butabekov","sequence":"additional","affiliation":[{"name":"Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tigay Zinaida","family":"Nikolaevna","sequence":"additional","affiliation":[{"name":"Republican Phthisiological Hospital 2, Nukus, Karakalpakstan, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Liverko","sequence":"additional","affiliation":[{"name":"Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nargiza","family":"Parpieva","sequence":"additional","affiliation":[{"name":"Republican Specialized Scientific and Practical Medical Center of Phthisiology and Pulmonology, Tashkent, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronelle","family":"Moodliar","sequence":"additional","affiliation":[{"name":"THINK (TB&amp;HIV Investigative Network): Doris Goodwin Hospital, Pietermaritzburg and Hillcrest, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varvara","family":"Solodovnikova","sequence":"additional","affiliation":[{"name":"Republican Research and Practical Centre for Pulmonology and TB, Minsk, Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Kazounis","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bern-Thomas","family":"Nyang'wa","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-3754","authenticated-orcid":true,"given":"Katherine L.","family":"Fielding","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology, London School of Hygiene &amp; Tropical Medicine (LSHTM), London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Berry","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","volume-title":"Global tuberculosis report 2023","author":"World Health Organization","year":"2023","unstructured":"World Health Organization. 2023. 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