Open Peer Review Discuss this article (0) Comments STUDY PROTOCOL Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial [version 1; referees: 1 approved with reservations] Huỳnh Thị Loan , Lam Minh Yen , Evelyne Kestelyn: , Nguyen Van Hao , Tran Tan Thanh , Nguyen Thi Phuong Dung , Hugo C. Turner , Ronald B. Geskus , Marcel Wolbers , Le Van Tan , H. Rogier Van Doorn , Nicholas P. Day , Duncan Wyncoll , Tran Tinh Hien , Guy E. Thwaites , Nguyen Van Vinh Chau , C. Louise Thwaites 2,3 Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK Medicine and Pharmacy, Hong Bang International University, Ho Chi Minh City, Vietnam Mahidol Oxford Research Unit, Bangkok, 10400, Thailand Guys and St Thomas’ Hospitals NHS Foundation Trust, London, SE1 7EH, UK Abstract Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: 1 2 2,3 1,4 2 2 2,3 2,3 2 2 2,3 3,5 6 2,3 2,3 1 2,3 1 2 3 4 5 6 Referee Status: Invited Referees version 2 published 05 Nov 2018 version 1 published 16 May 2018 1 report , Dalhousie Joanne M. Langley University, Canada 1 16 May 2018, :58 ( First published: 3 ) https://doi.org/10.12688/wellcomeopenres.14587.1 05 Nov 2018, :58 ( Latest published: 3 ) https://doi.org/10.12688/wellcomeopenres.14587.2 v1 Page 1 of 19 Wellcome Open Research 2018, 3:58 Last updated: 05 NOV 2018