PMID- 29996783 OWN - NLM STAT- MEDLINE DCOM- 20190416 LR - 20230820 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 18 IP - 1 DP - 2018 Jul 11 TI - Toxicity associated with tuberculosis chemotherapy in the REMoxTB study. PG - 317 LID - 10.1186/s12879-018-3230-6 [doi] LID - 317 AB - BACKGROUND: The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin. METHODS: All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment. RESULTS: In the standard therapy arm 57 (8.9%) of 639 patients experienced >/=1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms ("isoniazid arm" with moxifloxacin substituted for ethambutol & "ethambutol arm" with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91-1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55-7.14) were significantly associated with experiencing >/=1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced >/=1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59-6.10, p < 0.001). CONCLUSIONS: Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring. FAU - Tweed, Conor D AU - Tweed CD AUID- ORCID: 0000-0001-6021-8237 AD - MRC Clinical Trials Unit at University College London, London, UK. c.tweed@ucl.ac.uk. FAU - Crook, Angela M AU - Crook AM AD - MRC Clinical Trials Unit at University College London, London, UK. FAU - Amukoye, Evans I AU - Amukoye EI AD - Keya Medical Research Unit, Nairobi, Kenya. FAU - Dawson, Rodney AU - Dawson R AD - University of Cape Town Lung Institute, Cape Town, South Africa. FAU - Diacon, Andreas H AU - Diacon AH AD - TASK Applied Science, Cape Town, South Africa. FAU - Hanekom, Madeline AU - Hanekom M AD - TASK Applied Science, Cape Town, South Africa. FAU - McHugh, Timothy D AU - McHugh TD AD - Division of Infection and Immunity, University College London, London, UK. FAU - Mendel, Carl M AU - Mendel CM AD - TB Alliance, New York, USA. FAU - Meredith, Sarah K AU - Meredith SK AD - MRC Clinical Trials Unit at University College London, London, UK. FAU - Murphy, Michael E AU - Murphy ME AD - Division of Infection and Immunity, University College London, London, UK. FAU - Murthy, Saraswathi E AU - Murthy SE AD - Division of Infection and Immunity, University College London, London, UK. FAU - Nunn, Andrew J AU - Nunn AJ AD - MRC Clinical Trials Unit at University College London, London, UK. FAU - Phillips, Patrick P J AU - Phillips PPJ AD - Division of Pulmonology, University of San Francisco, San Francisco, USA. FAU - Singh, Kasha P AU - Singh KP AD - The Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. FAU - Spigelman, Melvin AU - Spigelman M AD - TB Alliance, New York, USA. FAU - Wills, Genevieve H AU - Wills GH AD - MRC Clinical Trials Unit at University College London, London, UK. FAU - Gillespie, Stephen H AU - Gillespie SH AD - University of St Andrews Medical School, St Andrews, UK. LA - eng GR - U01 AI069453/AI/NIAID NIH HHS/United States GR - OPP1017459/GATES/Bill & Melinda Gates Foundation/United States GR - UM1 AI068634/AI/NIAID NIH HHS/United States GR - U01 AI069469/AI/NIAID NIH HHS/United States GR - U01 AI069426/AI/NIAID NIH HHS/United States GR - UM1 AI106701/AI/NIAID NIH HHS/United States GR - UM1 AI068636/AI/NIAID NIH HHS/United States GR - MC_U122888469/MRC_/Medical Research Council/United Kingdom GR - MC_UU_12023/27/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20180711 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Antitubercular Agents) RN - 8G167061QZ (Ethambutol) RN - U188XYD42P (Moxifloxacin) RN - V83O1VOZ8L (Isoniazid) SB - IM MH - Adult MH - Antitubercular Agents/*adverse effects MH - Clinical Protocols MH - Ethambutol/*adverse effects MH - Female MH - HIV Seropositivity MH - Humans MH - Incidence MH - Isoniazid/*adverse effects MH - Male MH - Moxifloxacin/*adverse effects MH - Treatment Outcome MH - Tuberculosis, Pulmonary/*drug therapy PMC - PMC6042413 OTO - NOTNLM OT - Adverse events OT - Clinical trials OT - Toxicity OT - Tuberculosis COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: All patients provided written consent to any data and samples collected as part of the trial being used in further studies to improve the diagnosis and treatment of tuberculosis, as stated on the informed consent form for the study. Ethics approval was granted for REMoxTB by the ethics board at University College London, and at each of the study sites: Kenya: KEMRI Scientific Steering Committee. KEMRI Ethical Review Committee. South Africa: Medicines Controll Council, Pretoria. Pharma Ethics, Pretoria. University of Cape Town Human Research Ethics Committee, Cape Town. Biomedical Research Ethics Committee, Durban. Wits Human Research Ethics Committee, Johannesburg. Tanzania: Kilimanjaro Christian Medical College Research Ethics and Review Committee, Moshi. Mbeya Ethics and Research Committee, Mbeya. National Institute for Medical Research, Dar Es Salaam. Zambia: University of Zambia Biomedical Research Ethics Committee, Lusaka. China: Beijing Chest Hospital of Capital Medical University Ethics Committee, Beijing. Shanghai Pulmonary Hospital Ethics Committee, Shanghai. Tianjin CDC Biomedical Ethics Committee, Tianjin. India: Biomedical Ethics Committee, New Dehli. Institutional Ethics Committee, Mahatma Gandhi Medical College and Hospital, Jaipur. Mexico: Comite de Investigacion y Etica (Division de Ensenanza, Investigacion, Capacitacion, Etica y Calidad) Hospital General de Occidente, Jalisco. National Jewish Health, Denver USA. Thailand: Ethics Committees on Researches Involving Human Subjects, Rajavithi Hospital, Bangkok. The Khon Kaen University Ethics Committee for Human Research Faculty of Medicine, Khon Kaen University, Muang Khon Kaen. Ethical Review Committee for Research in Human Subjects, Ministry of Public Health, Nonthraburi. Ethical Review Committee of Chest Disease Institute, Department of Medical Services and Ministry of Public Health, Nonthraburi. Malaysia: Medical Research & Ethics Committee, Ministry of Health Malaysia, Kuala Lumpur. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors' declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/07/13 06:00 MHDA- 2019/04/17 06:00 PMCR- 2018/07/11 CRDT- 2018/07/13 06:00 PHST- 2018/02/07 00:00 [received] PHST- 2018/07/02 00:00 [accepted] PHST- 2018/07/13 06:00 [entrez] PHST- 2018/07/13 06:00 [pubmed] PHST- 2019/04/17 06:00 [medline] PHST- 2018/07/11 00:00 [pmc-release] AID - 10.1186/s12879-018-3230-6 [pii] AID - 3230 [pii] AID - 10.1186/s12879-018-3230-6 [doi] PST - epublish SO - BMC Infect Dis. 2018 Jul 11;18(1):317. doi: 10.1186/s12879-018-3230-6.