Efficacy and safety of iloprost in trauma patients with haemorrhagic shock-induced endotheliopathy-Protocol for the multicentre randomized, placebo-controlled, blinded, investigator-initiated shine-trauma trial.

Abstract

BackgroundTraumatic injury accounts for 800 000 deaths in the European Union annually. The main causes of deaths in trauma patients are exsanguination and multiple organ failure (MOF). We have studied >1000 trauma patients and identified shock‐induced endotheliopathy (SHINE), the pathophysiological mechanism responsible for MOF and high mortality. Pilot studies indicate that low‐dose iloprost (1 ng/kg/min) improves endothelial functionality in critically ill patients suggesting this intervention may improve patient outcome in traumatic SHINE.Material and MethodsThis is a multicentre, randomized, blinded clinical investigator‐initiated phase 2B trial in trauma patients with haemorrhagic shock‐induced endotheliopathy. Patients are randomized 1:1 to 72 hours infusion of iloprost 1 ng/kg/min or Placebo (equal volume of saline). A total of 220 trauma patients will be included. The primary endpoint is the number of intensive care unit (ICU)‐free days, within 28 days of admission. Secondary endpoints include 28‐ and 90‐day all‐cause mortality, hospital length of stay, vasopressor‐free days in the intensive care unit (ICU) within 28 days, ventilator‐free days in the ICU within 28 days, renal replacement‐free days in the ICU within 28 days, number of serious adverse reactions and serious adverse events within the first 4 days of admission.DiscussionThis trial will test the safety and efficacy of administration of iloprost vs placebo for 72 hours in trauma patients with haemorrhagic shock‐induced endotheliopathy. Trial endpoints focus on the potential effect of iloprost to reduce the need for ICU stay secondary to mitigation of organ failure.Trial registrationSHINE‐TRAUMA trial—EudraCT no. 2019‐000936‐24—Clinicaltrials.gov: NCT03903939 Ethics Committee no. H‐19014482.