Study protocol of a phase 2, randomised, placebo-controlled, double-blind, adaptive, parallel group clinical study to evaluate the efficacy and safety of recombinant alpha-1-microglobulin in subjects at high risk for acute kidney injury following open-chest cardiac surgery (AKITA trial)
Abstract
Introduction Acute kidney injury (AKI) is a common complication after cardiac surgery (CS) and is associated with adverse short-term and long-term outcomes. Alpha-1-microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme binding and mitochondrial-protective mechanisms.
RMC-035 is a modified, more soluble, variant of A1M and has been proposed as a novel targeted therapeutic protein to prevent CS-associated AKI (CS-AKI). RMC-035 was considered safe and generally well tolerated when evaluated in four clinical phase 1 studies.
Methods and analysis This is a phase 2, randomised, double-blind, adaptive design, parallel group clinical study that evaluates RMC-035 compared with placebo in approximately 268 cardiac surgical patients at high risk for CS-AKI. RMC-035 is administered as an intravenous infusion.
In total, five doses will be given. Dosing is based on presurgery estimated glomerular filtration rate (eGFR), and will be either 1.3 or 0.65mg/kg.The primary study objective is to evaluate whether RMC-035 reduces the incidence of postoperative AKI, and key secondary objectives are to evaluate whether RMC-035 improves postoperative renal function compared with placebo.
A blinded interim analysis with potential sample size reassessment is planned once 134 randomised subjects have completed dosing. An independent data monitoring committee will evaluate safety and efficacy data at prespecified intervals throughout the trial.
The study is a global multicentre study at approximately 30 sites. Ethics and dissemination The trial was approved by the joint ethics committee of the physician chamber Westfalen-Lippe and the University of Munster (code '2021-778f-A') and subsequently approved by the responsible ethics committees/relevant institutional review boards for the participating sites.
The study is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki and other applicable regulations. Results of this study will be published in a peer-reviewed scientific journal.