Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210000, Jiangsu, China.
National Institute of Healthcare Data Science, Nanjing University, Nanjing, 210010, Jiangsu, China.
Intensive Care Med. 2022 Jul;48(7):899-909. doi: 10.1007/s00134-022-06745-7. Epub 2022 Jun 17.
Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP.
We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission.
A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI - 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%).
The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.
感染性胰腺坏死（IPN）是急性坏死性胰腺炎（ANP）的一种高度致命的并发症。由于急性胰腺炎早期存在免疫抑制证据，免疫增强可能是一种治疗选择。本试验旨在评估早期免疫增强型胸腺素 alpha 1（Tα1）治疗是否可降低预测严重 ANP 患者 IPN 的发生率。
我们进行了一项多中心、双盲、随机、安慰剂对照试验，纳入了急性生理学和慢性健康评估 II 评分（APACHE II）≥8 分和计算机断层扫描（CT）严重程度评分≥5 分且在症状出现后 7 天内入院的 ANP 患者。入组患者被随机分配接受皮下注射 Tα1 1.6mg，每 12 小时一次，连用 7 天，随后每天一次，连用 7 天，或接受匹配的安慰剂（生理盐水）。主要结局是在本次住院期间发生 IPN。
共随机分配了 508 例患者，其中 254 例接受 Tα1 治疗，254 例接受安慰剂治疗。绝大多数患者需要入住重症监护病房（ICU）（479/508，94.3%）。在本次住院期间，Tα1 组有 40/254（15.7%）例患者发生 IPN，安慰剂组有 46/254 例（18.1%）患者发生 IPN（差异-2.4%[95%CI-7.4 至 5.1%]；p=0.48）。四个预先设定的亚组的结果相似。其他主要并发症（新发器官衰竭[10.6%比 15%]、出血[6.3%比 3.5%]和胃肠道瘘[2%比 2.4%]）也没有差异。
在本次住院期间，预测严重 ANP 患者的免疫增强 Tα1 治疗并未降低 IPN 的发生率。
