随机临床试验：一项为期 1 周、双盲、安慰剂对照的研究，评估了胰酶 25000 欧药典微球（Creon 25000 MMS）治疗胰腺手术后胰腺外分泌不足的疗效，研究有 1 年的开放标签扩展期。

Randomised clinical trial: a 1-week, double-blind, placebo-controlled study of pancreatin 25 000 Ph. Eur. minimicrospheres (Creon 25000 MMS) for pancreatic exocrine insufficiency after pancreatic surgery, with a 1-year open-label extension.

机构信息

Department of General, Visceral and Vascular Surgery, Josephs-Hospital Warendorf, Warendorf, Germany.

出版信息

Aliment Pharmacol Ther. 2013 Apr;37(7):691-702. doi: 10.1111/apt.12236. Epub 2013 Feb 5.

BACKGROUND

Pancreatic exocrine insufficiency (PEI) often occurs following pancreatic surgery.

AIM

To demonstrate the superior efficacy of pancreatin 25 000 minimicrospheres (Creon 25000 MMS; 9-15 capsules/day) over placebo in treating PEI after pancreatic resection.

METHODS

A 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study with a 1-year, open-label extension (OLE). Subjects ≥18 years old with PEI after pancreatic resection, defined as baseline coefficient of fat absorption (CFA) <80%, were randomised to oral pancreatin or placebo (9-15 capsules/day: 3 with main meals, 2 with snacks). In the OLE, all subjects received pancreatin. The primary efficacy measure was least squares mean CFA change from baseline to end of double-blind treatment (ancova).

RESULTS

All 58 subjects randomised (32 pancreatin, 26 placebo) completed double-blind treatment and entered the OLE; 51 completed the OLE. The least squares mean CFA change in the double-blind phase was significantly greater with pancreatin vs. placebo: 21.4% (95% CI: 13.7, 29.2) vs. -4.2% (-12.8, 4.5); difference 25.6% (13.9, 37.3), P < 0.001. The mean ± s.d. CFA increased from 53.6 ± 20.6% at baseline to 78.4 ± 20.7% at OLE end (P < 0.001). Treatment-emergent adverse events occurred in 37.5% subjects on pancreatin and 26.9% on placebo during double-blind treatment, with flatulence being the most common (pancreatin 12.5%, placebo 7.7%). Only two subjects discontinued due to treatment-emergent adverse events, both during the OLE.

CONCLUSIONS

This study demonstrates superior efficacy of pancreatin 25 000 over placebo in patients with PEI after pancreatic surgery, measured by change in CFA. Pancreatin was generally well tolerated at the high dose administered (EudraCT registration number: 2005-004854-29).

背景

胰腺外分泌不足（PEI）常发生于胰腺手术后。

目的

证明胰酶 25000 微囊（Creon 25000 MMS；每天 9-15 粒胶囊）治疗胰腺切除术后 PEI 的疗效优于安慰剂。

方法

这是一项为期 1 周的、双盲、随机、安慰剂对照、平行组、多中心研究，随后进行为期 1 年的开放标签扩展（OLE）。研究对象为胰腺切除术后存在 PEI 的年龄≥18 岁患者，定义为基线脂肪吸收系数（CFA）＜80%，他们被随机分配接受胰酶或安慰剂（每天 9-15 粒胶囊：3 粒随主餐服用，2 粒随零食服用）。在 OLE 中，所有患者均接受胰酶治疗。主要疗效指标为从双盲治疗开始到结束时的最小二乘均数 CFA 变化（协方差分析）。

结果

所有 58 例随机分组患者（胰酶组 32 例，安慰剂组 26 例）均完成双盲治疗并进入 OLE；51 例完成 OLE。双盲阶段胰酶组的 CFA 最小二乘均数变化明显大于安慰剂组：21.4%（95%CI：13.7，29.2）比-4.2%（-12.8，4.5）；差异 25.6%（13.9，37.3），P＜0.001。治疗开始时的平均 CFA 为 53.6±20.6%，OLE 结束时为 78.4±20.7%（P＜0.001）。在双盲治疗期间，胰酶组有 37.5%的患者和安慰剂组有 26.9%的患者出现治疗相关不良事件，最常见的是气胀（胰酶组 12.5%，安慰剂组 7.7%）。仅有 2 例患者因治疗相关不良事件在 OLE 期间停药。