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特利加压素联合白蛋白治疗1型肝肾综合征
Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome


Florence Wong ... 其他 • 2021.03.04

摘要


背景

血管收缩药特利加压素在全球许多地区被用于治疗1型肝肾综合征(HRS-1),也被纳入欧洲临床诊疗指南。

 

方法

我们开展了一项3期试验,目的是证实特利加压素+白蛋白联合治疗对HRS-1成人患者的疗效和安全性。我们以2∶1的比例将患者随机分组,两组分别接受最长14日的特利加压素或安慰剂治疗;并强烈建议两组均并用白蛋白。主要终点是经证实的HRS逆转,其定义为间隔至少2小时的连续两次血清肌酐测定值≤1.5 mg/dL,并且患者完成治疗后可在未接受肾脏替代治疗的情况下生存至少10日。考虑到多重比较,我们利用Hochberg方法分析了四项预设的次要终点。

 

结果

共计300例患者接受了随机分组(特利加压素组199例,安慰剂组101例)。特利加压素组63例患者(32%)和安慰剂组17例患者(17%)出现了经证实的HRS逆转(P=0.006)。关于预设的次要终点,特利加压素组78例患者(39%)和安慰剂组18例患者(18%)出现了HRS逆转,其定义为前14日期间出现血清肌酐水平≤1.5 mg/dL(P<0.001);截至第30日,两组分别有68例(34%)和17例(17%)患者在未接受肾脏替代治疗的情况下出现了HRS逆转(P=0.001);在全身性炎症反应综合征患者(特利加压素组84例患者,安慰剂组48例患者)中,两组分别有31例(37%)和3例(6%)患者出现了HRS逆转(P<0.001);截至第30日,两组分别有52例(26%)和17例(17%)患者出现了经证实的HRS逆转(P=0.08)。第90日时,特利加压素组46例患者(23%)和安慰剂组29例患者(29%)已接受了肝移植,两组分别有101例(51%)和45例(45%)患者死亡。特利加压素组的不良事件(包括腹痛、恶心、腹泻和呼吸衰竭)发生率高于安慰剂。特利加压素组22例患者(11%)和安慰剂组2例患者(2%)在90日死于呼吸系统疾病。

 

结论

在肝硬化合并HRS-1的成人患者中,试验结果表明特利加压素改善肾功能的效果优于安慰剂,但特利加压素组发生了包括呼吸衰竭在内的严重不良事件(由Mallinckrodt Pharmaceuticals资助,CONFIRM在ClinicalTrials.gov注册号为NCT02770716)。





作者信息

Florence Wong, M.B., B.S., M.D., S. Chris Pappas, M.D., J.D., Michael P. Curry, M.D., K. Rajender Reddy, M.D., Raymond A. Rubin, M.D., Michael K. Porayko, M.D., Stevan A. Gonzalez, M.D., Khalid Mumtaz, M.B., B.S., Nicholas Lim, M.D., Douglas A. Simonetto, M.D., Pratima Sharma, M.D., Arun J. Sanyal, M.B., B.S., M.D., Marlyn J. Mayo, M.D., R. Todd Frederick, M.D., Shannon Escalante, M.S., and Khurram Jamil, M.D. for the CONFIRM Study Investigators*
From the Department of Medicine, University of Toronto, Toronto (F.W.); Orphan Therapeutics, Annandale (S.C.P.), and Mallinckrodt Pharmaceuticals, Bedminster (S.E., K.J.) — both in New Jersey; the Department of Medicine, Beth Israel Deaconess Medical Center, Boston (M.P.C.); the University of Pennsylvania, Philadelphia (K.R.R.); Piedmont Transplant Institute, Piedmont Healthcare, Atlanta (R.A.R.); the Department of Medicine, Vanderbilt University Medical Center, Nashville (M.K.P.); the Department of Medicine, Baylor Scott and White All Saints Medical Center, Fort Worth (S.A.G.), and the Department of Medicine, University of Texas Southwestern Medical Center, Dallas (M.J.M.) — both in Texas; Ohio State University, Columbus (K.M.); the Department of Medicine, University of Minnesota, Minneapolis (N.L.), and the Department of Medicine, Mayo Clinic, Rochester (D.A.S.) — both in Minnesota; the Department of Medicine, University of Michigan Medical Center, Ann Arbor (P.S.); Virginia Commonwealth University, Richmond (A.J.S.); and Hepatology and Liver Transplantation, California Pacific Medical Center, San Francisco (R.T.F.). Address reprint requests to Dr. Wong at the Department of Medicine, University of Toronto, 200 Elizabeth St., Toronto, ON M5G 2C4, Canada, or at florence.wong@utoronto.ca. *A complete list of investigators in the CONFIRM Study are listed in the Supplementary Appendix, available at NEJM.org.

 

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