Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial

Wellcome Open Research

article

Huỳnh Thị Loan¹  Lam Minh Yen²  Evelyne Kestelyn:²  Nguyen Van Hao¹  Tran Tan Thanh²  Nguyen Thi Phuong Dung²  Hugo C. Turner²  Ronald B. Geskus²  Marcel Wolbers²  Le Van Tan²  H. Rogier Van Doorn²  Nicholas P. Day³  Duncan Wyncoll⁶  Tran Tinh Hien²  Guy E. Thwaites²  Nguyen Van Vinh Chau¹  C. Louise Thwaites² 

[1] Hospital for Tropical Diseases;Oxford University Clinical Research Unit, Hospital for Tropical Diseases;Centre for Tropical Medicine and Global Health, University of Oxford;Medicine and Pharmacy, Hong Bang International University;Mahidol Oxford Research Unit;Guys and St Thomas’ Hospitals NHS Foundation Trust

关键词: Tetanus;    management;    treatment;    intrathecal;    antitoxin;    human tetanus immunoglobulin;   

DOI  :  10.12688/wellcomeopenres.14587.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events.

【 授权许可】

CC BY