Department of Gastroenterological Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Department of Transplantation and Liver Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
JAMA Surg. 2020 Apr 1;155(4):291-298. doi: 10.1001/jamasurg.2019.6019.
Both hydrocortisone and pasireotide have been shown in randomized clinical trials to be effective in reducing postoperative complications of pancreatic surgery, but to date no randomized clinical trial has evaluated the effectiveness of pasireotide compared with hydrocortisone.
To assess the noninferiority of hydrocortisone compared with pasireotide in reducing complications after partial pancreatectomy.
DESIGN, SETTING, AND PARTICIPANTS: A noninferiority, parallel-group, individually randomized clinical trial was conducted at a single academic center between May 19, 2016, and December 17, 2018. Outcome collectors and analyzers were blinded. A total of 281 patients undergoing partial pancreatectomy were assessed for inclusion. Patients younger than 18 years, those allergic to hydrocortisone or pasireotide, patients undergoing pancreaticoduodenectomy with hard pancreas or dilated pancreatic duct, and patients not eventually undergoing partial pancreatectomy were excluded. Modified intention-to-treat analysis was used in determination of the results.
Treatment included pasireotide, 900 μg, subcutaneously twice a day for 7 days or hydrocortisone, 100 mg, intravenously 3 times a day for 3 days.
The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days. The noninferiority limit was set to 9 CCI points.
Of the 281 patients (mean [SD] age, 63.8 years) assessed for eligibility, 168 patients (mean [SD] age, 63.6 years) were randomized and 126 were included in the modified intention-to-treat analyses. Sixty-three patients received pasireotide (35 men [56%]; median [interquartile range] age, 64 [56-70] years) and 63 patients received hydrocortisone (25 men [40%]; median [interquartile range] age, 67 [56-73] years). The mean (SD) CCI score was 23.94 (17.06) in the pasireotide group and 30.11 (20.47) in the hydrocortisone group (mean difference, -6.16; 2-sided 90% CI, -11.73 to -0.60), indicating that hydrocortisone was not noninferior. Postoperative pancreatic fistula was detected in 34 patients (54%) in the pasireotide group and 39 patients (62%) in the hydrocortisone group (odds ratio, 1.39; 95% CI, 0.68-2.82; P = .37). One patient in the pasireotide group and 2 patients in the hydrocortisone group died within 30 days. In subgroup analyses of patients undergoing distal pancreatectomy, the CCI score was a mean of 10.3 points lower (mean [SD], 16.03 [11.94] vs 26.28 [21.76]; 2-sided 95% CI, -19.34 to -2.12; P = .03) and postoperative pancreatic fistula rate was lower (37% vs 67%; P = .02) in the pasireotide group compared with the hydrocortisone group.
In this study, hydrocortisone was not noninferior compared with pasireotide in patients undergoing partial pancreatectomy. Pasireotide may be more effective than hydrocortisone in patients undergoing distal pancreatectomy.
ClinicalTrials.gov identifier: NCT02775227; EudraCT identifier: 2016-000212-16.
已有随机临床试验表明，氢化可的松和培高利特在减少胰腺手术后并发症方面均有效，但迄今为止，尚无随机临床试验评估培高利特与氢化可的松相比的有效性。
评估在部分胰腺切除术后，氢化可的松与培高利特相比的非劣效性。
设计、设置和参与者：在 2016 年 5 月 19 日至 2018 年 12 月 17 日期间，在一家学术中心进行了一项非劣效性、平行组、个体随机临床试验。结果收集者和分析者均被设盲。共评估了 281 例接受部分胰腺切除术的患者是否符合纳入标准。年龄小于 18 岁、对氢化可的松或培高利特过敏、胰腺硬或胰管扩张行胰十二指肠切除术以及最终未行部分胰腺切除术的患者被排除在外。采用改良意向治疗分析来确定结果。
治疗包括培高利特，900μg，每天皮下注射 2 次，共 7 天，或氢化可的松，100mg，每天静脉注射 3 次，共 3 天。
主要结局是术后 30 天内的综合并发症指数（CCI）评分。非劣效性界限设定为 9 CCI 点。
在 281 例符合条件的患者（平均[标准差]年龄，63.8 岁）中，168 例（平均[标准差]年龄，63.6 岁）被随机分组，126 例被纳入改良意向治疗分析。63 例患者接受培高利特（35 例男性[56%]；中位[四分位间距]年龄，64 [56-70]岁），63 例患者接受氢化可的松（25 例男性[40%]；中位[四分位间距]年龄，67 [56-73]岁）。培高利特组的平均（标准差）CCI 评分为 23.94（17.06），氢化可的松组为 30.11（20.47）（平均差值，-6.16；双侧 90%置信区间，-11.73 至-0.60），表明氢化可的松不具有非劣效性。培高利特组有 34 例（54%）患者发生术后胰瘘，氢化可的松组有 39 例（62%）患者发生术后胰瘘（优势比，1.39；95%置信区间，0.68-2.82；P = 0.37）。培高利特组中有 1 例患者和氢化可的松组中有 2 例患者在术后 30 天内死亡。在接受远端胰腺切除术的患者亚组分析中，CCI 评分平均低 10.3 分（平均[标准差]，16.03 [11.94] vs 26.28 [21.76]；双侧 95%置信区间，-19.34 至-2.12；P = 0.03），术后胰瘘发生率较低（37% vs 67%；P = 0.02）。
在这项研究中，与氢化可的松相比，在接受部分胰腺切除术的患者中，培高利特不具有非劣效性。在接受远端胰腺切除术的患者中，培高利特可能比氢化可的松更有效。
ClinicalTrials.gov 标识符：NCT02775227；EudraCT 标识符：2016-000212-16。
