Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Tuberculosis, Shanghai Pulmonary Hospital, Shanghai, China.
Liver Int. 2022 Aug;42(8):1803-1813. doi: 10.1111/liv.15290. Epub 2022 May 25.
Evidence for using bicyclol in drug-induced liver injury (DILI) is limited. This study aimed to explore the efficacy and safety of bicyclol in acute DILI.
This was a multicenter, randomized, double-blinded, double-dummy, active-controlled, superiority and phase II trial. Patients with idiosyncratic acute DILI were randomized 1: 1:1 to low-dose bicyclol (25 mg times a day [TID]), high-dose bicyclol (50 mg TID) and polyene phosphatidylcholine (control) groups. The primary endpoint was the decrease from baseline in serum alanine aminotransferase (ALT) levels at post-treatment for 4 weeks.
Overall, 241 patients were included in the full analysis set, with 81, 82 and 78 patients in the low-dose bicyclol, high-dose bicyclol, and control groups respectively. ALT levels decreased across groups (-249.2 ± 151.1, -273.6 ± 203.1, and -180.8 ± 218.2 U/L in the low-dose bicyclol, high-dose bicyclol and control groups, respectively; both p < .001, the bicyclol-dependent groups vs. control group). The ALT normalization rates at weeks 1, 2, 4, 6 and 8 were higher in the bicyclol-dependent groups than in the control group (p = .002 at week 1 and all p < .001 at weeks 2, 4, 6 and 8 respectively). The median times to ALT normalization in the low-dose bicyclol, high-dose bicyclol and control groups were 29, 16 and 43 days respectively. Adverse events, serious adverse events and adverse drug reactions were similar across groups.
Bicyclol (25 and 50 mg TID) appeared efficacious and safe for treating idiosyncratic acute DILI, while bicyclol 50 mg TID showed higher efficacy.
www.
gov (registration no. NCT02944552).
目前针对药物性肝损伤（DILI）使用双环醇的证据有限。本研究旨在探索双环醇治疗急性 DILI 的疗效和安全性。
这是一项多中心、随机、双盲、双模拟、阳性对照、Ⅱ期临床试验。将特发性急性 DILI 患者按 1:1:1 随机分为低剂量双环醇（25mg，每日 3 次[TID]）、高剂量双环醇（50mg，TID）和多烯磷脂酰胆碱（对照）组。主要终点为治疗后 4 周时血清丙氨酸氨基转移酶（ALT）水平自基线的下降。
共有 241 例患者纳入全分析集，低剂量双环醇、高剂量双环醇和对照组分别有 81、82 和 78 例患者。各组 ALT 水平均下降（低剂量双环醇组、高剂量双环醇组和对照组分别为-249.2±151.1、-273.6±203.1 和-180.8±218.2 U/L；均 p<.001，双环醇依赖组与对照组比较）。双环醇依赖组在治疗第 1、2、4、6 和 8 周时的 ALT 正常化率均高于对照组（第 1 周时 p=.002，第 2、4、6 和 8 周时均 p<.001）。低剂量双环醇、高剂量双环醇和对照组的 ALT 正常化中位时间分别为 29、16 和 43 天。各组不良反应、严重不良反应和药物不良反应发生率相似。
双环醇（25 和 50mg，TID）治疗特发性急性 DILI 有效且安全，而双环醇 50mg，TID 显示出更高的疗效。
www.
gov（注册号：NCT02944552）。
