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Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial
BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might impr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115864/ https://www.ncbi.nlm.nih.gov/pubmed/35561721 http://dx.doi.org/10.1016/S2214-109X(22)00117-6 |
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author | Van Hao, Nguyen Loan, Huynh Thi Yen, Lam Minh Kestelyn, Evelyne Hong, Duc Du Thuy, Duong Bich Nguyen, Nguyen Thanh Duong, Ha Thi Hai Thuy, Tran Thi Diem Nhat, Phung Tran Huy Khanh, Phan Nguyen Quoc Dung, Nguyen Thi Phuong Phu, Nguyen Hoan Phong, Nguyen Thanh Lieu, Pham Thi Tuyen, Pham Thi Hanh, Bui Thi Bich Nghia, Ho Dang Trung Oanh, Pham Kieu Nguyet Tho, Phan Vinh Tan Thanh, Tran Turner, Hugo C van Doorn, H Rogier Van Tan, Le Wyncoll, Duncan Day, Nicholas PJ Geskus, Ronald B Thwaites, Guy E Van Vinh Chau, Nguyen Thwaites, C Louise |
author_facet | Van Hao, Nguyen Loan, Huynh Thi Yen, Lam Minh Kestelyn, Evelyne Hong, Duc Du Thuy, Duong Bich Nguyen, Nguyen Thanh Duong, Ha Thi Hai Thuy, Tran Thi Diem Nhat, Phung Tran Huy Khanh, Phan Nguyen Quoc Dung, Nguyen Thi Phuong Phu, Nguyen Hoan Phong, Nguyen Thanh Lieu, Pham Thi Tuyen, Pham Thi Hanh, Bui Thi Bich Nghia, Ho Dang Trung Oanh, Pham Kieu Nguyet Tho, Phan Vinh Tan Thanh, Tran Turner, Hugo C van Doorn, H Rogier Van Tan, Le Wyncoll, Duncan Day, Nicholas PJ Geskus, Ronald B Thwaites, Guy E Van Vinh Chau, Nguyen Thwaites, C Louise |
author_sort | Van Hao, Nguyen |
collection | PubMed |
description | BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. METHODS: In a 2 × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. FINDINGS: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66–1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75–1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. INTERPRETATION: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration. FUNDING: The Wellcome Trust. |
format | Online Article Text |
id | pubmed-9115864 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-91158642022-06-14 Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial Van Hao, Nguyen Loan, Huynh Thi Yen, Lam Minh Kestelyn, Evelyne Hong, Duc Du Thuy, Duong Bich Nguyen, Nguyen Thanh Duong, Ha Thi Hai Thuy, Tran Thi Diem Nhat, Phung Tran Huy Khanh, Phan Nguyen Quoc Dung, Nguyen Thi Phuong Phu, Nguyen Hoan Phong, Nguyen Thanh Lieu, Pham Thi Tuyen, Pham Thi Hanh, Bui Thi Bich Nghia, Ho Dang Trung Oanh, Pham Kieu Nguyet Tho, Phan Vinh Tan Thanh, Tran Turner, Hugo C van Doorn, H Rogier Van Tan, Le Wyncoll, Duncan Day, Nicholas PJ Geskus, Ronald B Thwaites, Guy E Van Vinh Chau, Nguyen Thwaites, C Louise Lancet Glob Health Articles BACKGROUND: Intramuscular antitoxin is recommended in tetanus treatment, but there are few data comparing human and equine preparations. Tetanus toxin acts within the CNS, where there is limited penetration of peripherally administered antitoxin; thus, intrathecal antitoxin administration might improve clinical outcomes compared with intramuscular injection. METHODS: In a 2 × 2 factorial trial, all patients aged 16 years or older with a clinical diagnosis of generalised tetanus admitted to the intensive care unit of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, were eligible for study entry. Participants were randomly assigned first to 3000 IU human or 21 000 U equine intramuscular antitoxin, then to either 500 IU intrathecal human antitoxin or sham procedure. Interventions were delivered by independent clinicians, with attending clinicians and study staff masked to treatment allocations. The primary outcome was requirement for mechanical ventilation. The analysis was done in the intention-to-treat population. The study is registered at ClinicalTrials.gov, NCT02999815; recruitment is completed. FINDINGS: 272 adults were randomly assigned to interventions between Jan 8, 2017, and Sept 29, 2019, and followed up until May, 2020. In the intrathecal allocation, 136 individuals were randomly assigned to sham procedure and 136 to antitoxin; in the intramuscular allocation, 109 individuals were randomly assigned to equine antitoxin and 109 to human antitoxin. 54 patients received antitoxin at a previous hospital, excluding them from the intramuscular antitoxin groups. Mechanical ventilation was given to 56 (43%) of 130 patients allocated to intrathecal antitoxin and 65 (50%) of 131 allocated to sham procedure (relative risk [RR] 0·87, 95% CI 0·66–1·13; p=0·29). For the intramuscular allocation, 48 (45%) of 107 patients allocated to human antitoxin received mechanical ventilation compared with 48 (44%) of 108 patients allocated to equine antitoxin (RR 1·01, 95% CI 0·75–1·36, p=0·95). No clinically relevant difference in adverse events was reported. 22 (16%) of 136 individuals allocated to the intrathecal group and 22 (11%) of 136 allocated to the sham procedure experienced adverse events related or possibly related to the intervention. 16 (15%) of 108 individuals allocated to equine intramuscular antitoxin and 17 (16%) of 109 allocated to human antitoxin experienced adverse events related or possibly related to the intervention. There were no intervention-related deaths. INTERPRETATION: We found no advantage of intramuscular human antitoxin over intramuscular equine antitoxin in tetanus treatment. Intrathecal antitoxin administration was safe, but did not provide overall benefit in addition to intramuscular antitoxin administration. FUNDING: The Wellcome Trust. Elsevier Ltd 2022-05-10 /pmc/articles/PMC9115864/ /pubmed/35561721 http://dx.doi.org/10.1016/S2214-109X(22)00117-6 Text en © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Articles Van Hao, Nguyen Loan, Huynh Thi Yen, Lam Minh Kestelyn, Evelyne Hong, Duc Du Thuy, Duong Bich Nguyen, Nguyen Thanh Duong, Ha Thi Hai Thuy, Tran Thi Diem Nhat, Phung Tran Huy Khanh, Phan Nguyen Quoc Dung, Nguyen Thi Phuong Phu, Nguyen Hoan Phong, Nguyen Thanh Lieu, Pham Thi Tuyen, Pham Thi Hanh, Bui Thi Bich Nghia, Ho Dang Trung Oanh, Pham Kieu Nguyet Tho, Phan Vinh Tan Thanh, Tran Turner, Hugo C van Doorn, H Rogier Van Tan, Le Wyncoll, Duncan Day, Nicholas PJ Geskus, Ronald B Thwaites, Guy E Van Vinh Chau, Nguyen Thwaites, C Louise Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title | Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title_full | Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title_fullStr | Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title_full_unstemmed | Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title_short | Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
title_sort | human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 × 2 factorial randomised controlled trial |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115864/ https://www.ncbi.nlm.nih.gov/pubmed/35561721 http://dx.doi.org/10.1016/S2214-109X(22)00117-6 |
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