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
Issued Date
2022-06-01
Resource Type
eISSN
2214109X
Scopus ID
2-s2.0-85129963818
Pubmed ID
35561721
Journal Title
The Lancet Global Health
Volume
10
Issue
6
Start Page
e862
End Page
e872
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet Global Health Vol.10 No.6 (2022) , e862-e872
Suggested Citation
Van Hao N., Loan H.T., Yen L.M., Kestelyn E., Hong D.D., Thuy D.B., Nguyen N.T., Duong H.T.H., Thuy T.T.D., Nhat P.T.H., Khanh P.N.Q., Dung N.T.P., Phu N.H., Phong N.T., Lieu P.T., Tuyen P.T., Hanh B.T.B., Nghia H.D.T., Oanh P.K.N., Tho P.V., Tan Thanh T., Turner H.C., van Doorn H.R., Van Tan L., Wyncoll D., Day N.P., Geskus R.B., Thwaites G.E., Van Vinh Chau N., Thwaites C.L. 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. The Lancet Global Health Vol.10 No.6 (2022) , e862-e872. e872. doi:10.1016/S2214-109X(22)00117-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/85831
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
Author(s)
Van Hao N.
Loan H.T.
Yen L.M.
Kestelyn E.
Hong D.D.
Thuy D.B.
Nguyen N.T.
Duong H.T.H.
Thuy T.T.D.
Nhat P.T.H.
Khanh P.N.Q.
Dung N.T.P.
Phu N.H.
Phong N.T.
Lieu P.T.
Tuyen P.T.
Hanh B.T.B.
Nghia H.D.T.
Oanh P.K.N.
Tho P.V.
Tan Thanh T.
Turner H.C.
van Doorn H.R.
Van Tan L.
Wyncoll D.
Day N.P.
Geskus R.B.
Thwaites G.E.
Van Vinh Chau N.
Thwaites C.L.
Loan H.T.
Yen L.M.
Kestelyn E.
Hong D.D.
Thuy D.B.
Nguyen N.T.
Duong H.T.H.
Thuy T.T.D.
Nhat P.T.H.
Khanh P.N.Q.
Dung N.T.P.
Phu N.H.
Phong N.T.
Lieu P.T.
Tuyen P.T.
Hanh B.T.B.
Nghia H.D.T.
Oanh P.K.N.
Tho P.V.
Tan Thanh T.
Turner H.C.
van Doorn H.R.
Van Tan L.
Wyncoll D.
Day N.P.
Geskus R.B.
Thwaites G.E.
Van Vinh Chau N.
Thwaites C.L.
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
Oxford University Clinical Research Unit
University of Medicine and Pharmacy at HCMC
University College London Hospitals NHS Foundation Trust
Imperial College London
Nuffield Department of Medicine
Guy's and St Thomas' NHS Foundation Trust
Pham Ngoc Thach University of Medicine
Oxford University Clinical Research Unit
University of Medicine and Pharmacy at HCMC
University College London Hospitals NHS Foundation Trust
Imperial College London
Nuffield Department of Medicine
Guy's and St Thomas' NHS Foundation Trust
Pham Ngoc Thach University of Medicine
Other Contributor(s)
Abstract
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.