Efficacy and safety of SP16 in preventing Acute Kidney Injury in at-risk subjects with chronic kidney disease undergoing elective cardiac surgery using the heart-lung-machine (EASE-AKI): study protocol for a prospective, randomised, double-blind, placebo-controlled clinical trial

Background: Cardiac surgery using cardiopulmonary bypass uses controlled hypoperfusion which leads to relative organ damage. Acute kidney injury is the most frequent and most important organ failure, in particular in patients with chronic kidney disease. To date, there are no approved drug treatments that could effectively prevent acute kidney injury. SP16, an agonist of the low-density lipoprotein receptor-related protein 1, has been shown to exert both reno- and cardioprotective effects in preclinical trials. Early clinical use of SP16 in phase I trials was safe. Administration of SP16 had beneficial trends on inflammatory response and infarct size in patients with ST-segment elevation myocardial infarction. The primary objective of this phase IIa trial is to demonstrate that injection of SP16 is safe and superior to placebo in preventing cardiac surgery-associated acute kidney injury within 7 days after surgery. Methods: This randomised, double-blinded, placebo-controlled, single centre study evaluates the efficacy and safety of SP16 in 120 high-risk chronic kidney disease patients with disease stadium G2-G3b undergoing cardiac surgery who are randomised into one of two treatment groups in a 1:1 ratio: SP16 (12 mg) or placebo. The study medication is administered via two subcutaneous injections, with the first dose given before surgery, followed by an additional dose after 9 h. Primary endpoints are the incidence of acute kidney injury during 7 days post-surgery and the frequency of adverse events within 72 h after index surgery. Important secondary endpoints include the incidence of major adverse kidney events at day 90 and impact on cardiac function. Safety assessments encompass adverse events, vital signs, electrocardiograms and routine safety laboratory tests. Additional evaluations include pharmacokinetics and immunological biomarkers. Discussion: This single-centre phase IIa trial will assess the incidence of cardiac surgery-associated acute kidney injury, describing the renoprotective potential of SP16 and its safety profile in patients undergoing cardiac surgery.