在重症急性胰腺炎早期进行人重组活化蛋白C（希加曲班）24小时输注：XIG-AP 1试验。

Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial.

作者信息

Miranda Charles J, Mason James M, Babu Benoy I, Sheen Aali J, Eddleston Jane M, Parker Michael J, Pemberton Philip, Siriwardena Ajith K

机构信息

Hepatobiliary Surgical Unit, Manchester Royal Infirmary, Manchester, UK.

Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.

出版信息

Pancreatology. 2015 Nov-Dec;15(6):635-41. doi: 10.1016/j.pan.2015.10.001. Epub 2015 Oct 20.

DOI:10.1016/j.pan.2015.10.001

PMID:26547592

Abstract

OBJECTIVE

Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis.

DESIGN

Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 μg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses.

RESULTS

Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion.

CONCLUSIONS

A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis.

TRIAL REGISTRATION

Eudract Number 2007-003635-23.

摘要

目的

尽管重症急性胰腺炎患者存在强烈的全身炎症反应，可能从治疗中获益，但由于担心胰腺出血，他们被排除在人重组活化蛋白C（Xigris）的主要试验之外。本研究的目的是提供评估Xigris用于重症急性胰腺炎的初步安全性数据。

设计

2009年11月至2011年10月的前瞻性临床试验。除标准临床护理外，患者通过静脉输注（24μg/kg/h）接受人重组活化蛋白C（Xigris）治疗24小时。使用在同一医院科室接受治疗的匹配历史对照组来比较结果。在166例连续入院的患者中，43例符合重症急性胰腺炎的筛查标准，19例被招募，所有患者均纳入分析。

结果

与历史对照组相比，Xigris组的出血事件较少，尽管这一发现未达到统计学意义（Xigris组为0%，对照组为21%，p = 0.13），同样，治疗组进一步干预的频率似乎也较低（11%对47%，p = 0.07）。接受Xigris治疗的患者住院时间较短（19天对41天，p = 0.03），使用血管活性药物的情况也是如此（5%对32%，p = 0.02）；两组的死亡率和感染发生率相似。输注后生物标志物蛋白C升高而IL-6降低。