Schefold Joerg C, Perner Anders, Lange Theis, Wetterslev Jørn, Wise Matt P, Borthwick Mark, Bendel Stepani, Keus Frederik, Guttormsen Anne Berit, Marker Søren, Krag Mette, Møller Morten Hylander
Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse 18, CH 3010, Bern, Switzerland.
Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Trials. 2018 Jan 10;19(1):26. doi: 10.1186/s13063-017-2408-3.
Proton pump inhibitors are often used in critically ill patients to prevent gastrointestinal bleeding despite limited evidence for benefit. Patients with acute kidney injury requiring renal replacement therapy (RRT) are at high risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through effects on platelets and coagulation cascades. No high-quality randomized clinical trials have previously assessed the benefits and harms of prophylactic proton pump inhibitor use in this high-risk population of adult critically ill patients.
METHODS/DESIGN: Among the 3350 patients included in the Stress Ulcer Prophylaxis in the Intensive Care Unit (SUP-ICU) trial-an investigator-initiated international randomized clinical trial on prophylactic proton pump inhibitor versus placebo in acutely admitted adult ICU patients at risk of gastrointestinal bleeding-we will compare the benefits and harms of prophylactic use of proton pump inhibitor in patients in need of RRT versus those not requiring this treatment. We will determine the proportion of patients with clinically important bleeding, the proportion of patients with adverse events including pneumonia, Clostridium difficile enteritis, or acute myocardial ischemia in the ICU, as well as transfusion requirements. Moreover, 90 day and 365 day mortality post-randomization will be investigated. As a secondary analysis, we will examine the association between acute kidney injury and RRT during ICU stay and gastrointestinal bleeding.
With the outlined predefined analysis, we will characterize the balance between the benefits and harms of stress ulcer prophylaxis in acutely admitted adult ICU patients in need of RRT, including the potential interaction of allocation to proton pump inhibitor versus placebo.
ClinicalTrials.gov, NCT02718261 . Registered on 14 March 2016.
尽管获益证据有限，但质子泵抑制剂常用于重症患者以预防胃肠道出血。需要肾脏替代治疗（RRT）的急性肾损伤患者发生胃肠道出血的风险很高，因为（预）尿毒症通过对血小板和凝血级联反应的影响诱发凝血病。此前尚无高质量随机临床试验评估在这一高危成年重症患者群体中预防性使用质子泵抑制剂的利弊。
方法/设计：在重症监护病房应激性溃疡预防（SUP-ICU）试验纳入的3350例患者中——这是一项由研究者发起的国际随机临床试验，比较急性入院有胃肠道出血风险的成年重症监护病房患者预防性使用质子泵抑制剂与安慰剂的效果——我们将比较需要RRT的患者与不需要这种治疗的患者预防性使用质子泵抑制剂的利弊。我们将确定发生具有临床意义出血的患者比例、发生不良事件（包括肺炎、艰难梭菌肠炎或重症监护病房急性心肌缺血）的患者比例以及输血需求。此外，还将调查随机分组后90天和365天的死亡率。作为一项次要分析，我们将研究重症监护病房住院期间急性肾损伤和RRT与胃肠道出血之间的关联。
通过概述的预定义分析，我们将描述在需要RRT的急性入院成年重症监护病房患者中应激性溃疡预防的利弊平衡，包括分配使用质子泵抑制剂与安慰剂的潜在相互作用。
ClinicalTrials.gov，NCT02718261。于2016年3月14日注册。
