University Neurosurgical Center Holland, Leiden University Medical Center, Haaglanden Medical Center and Haga Teaching Hospital, Albinusdreef 2, J-11-R-83, 2333 ZA, Leiden, Hague, The Netherlands.
Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Trials. 2021 Dec 4;22(1):874. doi: 10.1186/s13063-021-05833-1.
Traumatic brain injury (TBI) is a major cause of death and disability across all ages. After the primary impact, the pathophysiologic process of secondary brain injury consists of a neuroinflammation response that critically leads to irreversible brain damage in the first days after the trauma. A key catalyst in this inflammatory process is the complement system. Inhibiting the complement system could therefore be a therapeutic target in TBI.
To study the safety and efficacy of C1-inhibitor (C1-INH) compared to placebo in patients with TBI. By temporarily blocking the complement system, we hypothesize a decrease in the posttraumatic neuroinflammatory response resulting in a less unfavorable clinical outcome for TBI patients.
CIAO@TBI is a multicenter, randomized, blinded, phase II placebo-controlled trial. Adult TBI patients with GCS < 13 requiring intracranial pressure (ICP) monitoring will be randomized, using block randomization, within 12 h after trauma to one dose 6000 IU C1-INH or placebo. A total of 106 patients will be included, and follow-up will occur up to 12 months. The primary endpoints are (1) Therapy Intensity Level (TIL) Scale, (2) Glasgow Outcome Scale-Extended (GOSE) at 6 months, and (3) complication rate during hospitalization. Outcomes will be determined by a trial nurse blinded for the treatment allocation. Analyses will be conducted in an intention-to-treat analysis.
We expect that C1-INH administration will be safe and potentially effective to improve clinical outcomes by reducing neuroinflammation in TBI patients.
ClinicalTrials.gov NCT04489160. Registered on 27 July 2020. EudraCT 2020-000140-58.
颅脑创伤（TBI）是全年龄段人群死亡和残疾的主要原因。原发性损伤后，继发性脑损伤的病理生理过程包括神经炎症反应，这在创伤后最初几天内会导致不可逆转的脑损伤。补体系统是这一炎症过程中的关键催化剂。因此，抑制补体系统可能是 TBI 的治疗靶点。
研究 C1 抑制剂（C1-INH）与安慰剂在 TBI 患者中的安全性和疗效。通过暂时阻断补体系统，我们假设创伤后神经炎症反应减少，从而使 TBI 患者的临床结局更有利。
CIAO@TBI 是一项多中心、随机、双盲、II 期安慰剂对照试验。GCS<13 需要颅内压（ICP）监测的成年 TBI 患者将在创伤后 12 小时内使用区组随机化方法随机分为 6000IU C1-INH 或安慰剂组。共纳入 106 例患者，随访时间最长至 12 个月。主要终点是（1）治疗强度量表（TIL），（2）6 个月时的格拉斯哥结局量表-扩展版（GOSE），和（3）住院期间的并发症发生率。结果将由对治疗分配不知情的试验护士确定。分析将采用意向治疗分析。
我们预计 C1-INH 给药将是安全的，并且有可能通过减少 TBI 患者的神经炎症来改善临床结局。
ClinicalTrials.gov NCT04489160。于 2020 年 7 月 27 日注册。EudraCT 2020-000140-58。
