Yang Chun, Zhu Jixiang, Zhang Yingying, Li Feng, Ni Kun, Xu Ke, Li Quanye, Ma Zhengliang, Yin Mingzhu
Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng, Jiangsu, China.
BMJ Open. 2025 Aug 11;15(8):e102904. doi: 10.1136/bmjopen-2025-102904.
Sepsis-induced coagulopathy (SIC) is an early-stage coagulation disorder associated with increased morbidity and mortality in sepsis. It reflects a dysregulated host response and is considered a precursor to disseminated intravascular coagulation and multi-organ failure. Currently, there is no specific treatment for SIC beyond supportive care. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that has shown potential in regulating inflammation and coagulation pathways. This study aims to evaluate the efficacy and safety of taVNS in improving coagulation dysfunction in patients with SIC, with the primary outcome being the proportion of patients achieving a ≥2-point improvement in SIC score by day 7.
This is a single-centre, randomised, sham-controlled, single-blind clinical trial designed to evaluate the efficacy of taVNS in patients with SIC. This study will enrol 184 adult patients who meet the diagnostic criteria for SIC. Participants will be randomly assigned in a 1:1 ratio to receive either active taVNS or sham stimulation for 7 consecutive days. The intervention will be applied twice daily for 7 consecutive days using standardised stimulation parameters (25 Hz, 3 mA, 60 min/session). The primary outcome is the proportion of patients achieving an improvement of ≥2 points in SIC score from baseline to day 7. Secondary outcomes include platelet count, international normalised ratio, activated partial thromboplastin time, D-dimer, fibrinogen, procalcitonin, C-reactive protein, interleukin-6, angiopoietin-2, systemic immune-inflammation index, lactic acid, duration of antibiotic therapy, length of hospital stay and 28-day all-cause mortality. Adverse events and protocol adherence will also be recorded. Data will be analysed using intention-to-treat principles. Between-group comparisons for the primary outcome will be performed using X tests. Repeated measures analysis of variance will be used for longitudinal secondary outcomes.
The study protocol has been approved by the Ethics Committee of Yancheng Third People's Hospital (approval No. 2023-058-01). The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2400082378). Findings will be disseminated through peer-reviewed publications and academic conferences.
ChiCTR2400082378.
脓毒症诱导的凝血病（SIC）是一种早期凝血障碍，与脓毒症患者发病率和死亡率增加相关。它反映了宿主反应失调，被认为是弥散性血管内凝血和多器官功能衰竭的先兆。目前，除了支持治疗外，尚无针对SIC的特异性治疗方法。经皮耳迷走神经刺激（taVNS）是一种非侵入性神经调节技术，已显示出在调节炎症和凝血途径方面的潜力。本研究旨在评估taVNS改善SIC患者凝血功能障碍的疗效和安全性，主要结局是在第7天SIC评分改善≥2分的患者比例。
这是一项单中心、随机、假刺激对照、单盲临床试验，旨在评估taVNS对SIC患者的疗效。本研究将纳入184例符合SIC诊断标准的成年患者。参与者将按1:1比例随机分配，连续7天接受主动taVNS或假刺激。干预将使用标准化刺激参数（25Hz，3mA，60分钟/疗程），每天应用两次，连续7天。主要结局是从基线到第7天SIC评分改善≥2分的患者比例。次要结局包括血小板计数、国际标准化比值、活化部分凝血活酶时间、D-二聚体、纤维蛋白原、降钙素原、C反应蛋白、白细胞介素-6、血管生成素-2、全身免疫炎症指数、乳酸、抗生素治疗持续时间、住院时间和28天全因死亡率。还将记录不良事件和方案依从性。数据将采用意向性分析原则进行分析。主要结局的组间比较将采用X检验。重复测量方差分析将用于纵向次要结局。
本研究方案已获得盐城市第三人民医院伦理委员会批准（批准号：2023-058-01）。该试验已在中国临床试验注册中心注册（注册号：ChiCTR2400082378）。研究结果将通过同行评审出版物和学术会议进行传播。
ChiCTR2400082378。
