An International, Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Trial on the Effects of EA-230 on the Length of Hospital Stay Following On-Pump Coronary Artery Bypass Grafting Surgery

Prior treatment

• Patients undergoing non-elective on-pump CABG (i.e., emergency surgery). Emergency surgery is defined as planned surgery within 24 hours of diagnosis.
• Previous receipt of EA-230.
• Use of any investigational drug within 1 month or 5 half-lives of said investigational drug (whichever is longer) prior to IMP administration in this trial. Participation in an observational clinical trial is not exclusionary.
• Cardiogenic shock or hemodynamic instability that requires inotropes, vasopressors, or other mechanical devices, such as an intra-aortic balloon counter-pulsation (IABP), within 24 hours prior to surgery.
• Use of a left ventricular assist device (LVAD), or intra-aortic balloon pump or other cardiac devices, within 7 days prior to surgery.
• A requirement for any of the following within 7 days prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, or other forms of mechanical circulatory support.
• Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery.
• Confirmed or treated endocarditis requiring antimicrobial or antiviral treatment within 30 days prior to surgery or other current active infection requiring antimicrobial or antiviral treatment within 14 days prior to surgery.
• Ongoing sepsis (as defined by SEPSIS-3) within 2 weeks of screening or, in the opinion of the investigator, an untreated clinically significant infection (viral or bacterial) prior to or at Screening and before randomization.
• Immuno-compromised patients, as self-reported or as observed in medical records, including patients: a. with solid organ transplantation. b. known to be positive for human immunodeficiency virus (HIV). c. that use immunosuppressive drugs or have received recent chemotherapy, at the discretion of the Investigator and including patients; i. with active malignancy who have undergone chemotherapy within 30 days prior to trial entry. ii. receiving chronic corticosteroid treatment equivalent to a prednisone dose of 10 mg or higher per day, within 30 days prior to trial entry, or an equivalent dose of another corticosteroid or any other anti-inflammatory or inflammation-suppressing medications such as interleukin blockers, methotrexate or similar therapies. Non-Steroidal Anti-Inflammatory Drugs are not exclusionary.

Other illness

• Patients with hematological disorders (known disorders from myeloid and/or lymphoid origin, leucopenia (both active and in remission)).
• Known hypersensitivity to the IMP.
• Any other condition which, in the Investigator’s opinion, will interfere with completion of the trial.
• Known chronic liver disorder with Child-Pugh C classification.

Lab values

• Known severe renal disease requiring dialysis, or a known estimated Glomerular Filtration Rate (eGFR) prior to admission of < 20 ml/min/1.73 m2.

Other

• Women who are pregnant, breastfeeding or planning to become pregnant during the trial or within 28 days after IMP administration.
• Patients (or partners of patients) not willing to use a reliable method of contraception from enrollment and up to 28 days after IMP administration.
• Patients who are unable to communicate effectively in the local language of the trial site, at the discretion of the Investigator.
• Inability to personally provide written informed consent
• Known or suspected of not being able to comply with the trial protocol, at the discretion of the Investigator.
• Being an employee of the Investigator or trial site with direct involvement in the proposed trial or other studies under the direction of that Investigator or trial site or being a family member of an employee of the Investigator with direct involvement in the proposed trial.

• Patients aged ≥18 years, both male and female.
• Patients scheduled for elective on-pump CABG with at least 3 bypasses, with or without valve replacement.
• For women of childbearing potential (WOCBP), agree to use adequate contraception from enrollment and up to 28 days after IMP administration, and must have a negative pregnancy test prior to entry into the trial
• For male patients, agree to use adequate contraception and refrain from donating sperm from enrollment and up to 28 days after IMP administration.
• Willing and able to give written informed consent