JMIR Publications

ABSTRACT

Background:

The cardiac surgery-induced systemic inflammatory response may induce post-operative hemodynamic instability and impairment of renal function. EA-230, a linear tetrapeptide (A-Q-G-V), is derived from the β-chain of the human chorionic gonadotropin pregnancy hormone. It has shown immunomodulatory and renoprotective effects in several animal models of systemic inflammation. In phase I and phase IIa studies these immunomodulatory effects were confirmed during human experimental endotoxaemia and EA-230 was found to have an excellent safety profile.

Objective:

This is the first-in-patient-study in which the safety and tolerability, immunomodulatory and renoprotective effects of EA-230 will be tested in a proof-of-principle design in patients with systemic inflammation following on-pump cardiac surgery.

Methods:

We describe a prospective, randomized, double-blind, placebo-controlled study in which 180 elective patients, undergoing on-pump coronary artery bypass grafting, with or without concomitant valve surgery, are enrolled. Patients will be randomized in a 1:1 ratio and will receive either EA-230, 90 mg/kg/hour, or a placebo. These will be infused at the start of the surgical procedure until the end of the use of the cardiopulmonary bypass. The main focus in this first-in-patient study will be on safety and tolerability of EA-230. the primary efficacy endpoint is the modulation of the inflammatory response by EA-230 quantified as the change in interleukin-6 plasma concentrations after surgery. The key secondary endpoint is effect of EA-230 on renal function. The study will be conducted in two parts to enable an interim safety analysis by an independent data monitoring committee at n=60. An adaptive design is used to re-assess statistical power halfway through the study.

Results:

This study has been approved by the independent competent authority and ethics committee and will be conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice and European Directive 2001/20/CE regarding the conduct of clinical trials. Results of this study will be submitted for publication in a peer-reviewed scientific journal. Enrollment of this study commenced in July 2016 and results are expected at the end of 2018.

Conclusions:

This adaptive phase 2 clinical study is designed to test the safety and tolerability of EA-230 in patients undergoing cardiac surgery. In addition, efficacy endpoints focused on the effect on the systemic inflammatory response and renal function are investigated. Clinical Trial: Clinicaltrials.gov NCT03145220; (https://clinicaltrials.gov/ct2/show/NCT03145220) (Archived by WebCite at http://www.webcitation.org/74JPh8GNN)