Loan Huỳnh Thị, Yen Lam Minh, Kestelyn Evelyne, Hao Nguyen Van, Thanh Tran Tan, Dung Nguyen Thi Phuong, Turner Hugo C, Geskus Ronald B, Wolbers Marcel, Tan Le Van, Van Doorn H Rogier, Day Nicholas P, Wyncoll Duncan, Hien Tran Tinh, Thwaites Guy E, Vinh Chau Nguyen Van, Thwaites C Louise
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Wellcome Open Res. 2018 Nov 5;3:58. doi: 10.12688/wellcomeopenres.14587.2. eCollection 2018.
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. ClinicalTrials.gov NCT02999815 21 December 2016.
尽管破伤风有效疫苗早已问世，但在许多国家，破伤风仍是一个严重问题。治疗结果取决于能否获得机械通气和重症监护设施，在这些资源有限的地区，死亡率仍然很高。破伤风抗毒素肌内注射是破伤风的推荐治疗方法，但由于破伤风毒素在中枢神经系统内起作用，有人认为鞘内注射抗毒素可能有益。先前的研究已表明其益处，但除一项小型试验外，尚未进行过双盲研究。本研究的目的是确定添加鞘内注射破伤风抗毒素是否能减少破伤风患者对机械通气的需求。次要目标：确定添加鞘内注射破伤风抗毒素是否能减少自主神经系统功能障碍以及住院/重症监护病房的住院时间；鞘内注射破伤风抗毒素用于治疗破伤风是否安全且具有成本效益；提供数据以支持推荐使用人源而非马源抗毒素。本研究将纳入胡志明市热带病医院收治的成年破伤风患者（≥16岁）。该研究是一项2×2析因双盲随机对照试验。符合条件的患者将以1:1:1:1的方式随机分配至四个治疗组（鞘内治疗加人源肌内治疗、鞘内治疗加马源肌内治疗、假手术加人源肌内治疗、假手术加马源肌内治疗）。主要结局指标将是对机械通气的需求。次要结局指标：住院/重症监护病房的住院时间、机械通气时间、住院期间及240天的死亡率和残疾情况、新抗生素处方、呼吸机相关性肺炎和自主神经系统功能障碍的发生率、苯二氮䓬类药物和哌库溴铵的总剂量以及不良事件的发生率。ClinicalTrials.gov标识符：NCT02999815，2016年12月21日。
