A phase II randomized, double-blind, placebo-controlled, multi-center study to evaluate tolerability, safety pharmacokinetics and efficacy of intravenous INO-1001 in high-risk subjects undergoing cardiopulmonary by-pass for coronary revascularization and/or valve surgery.

INTERVENTION: Product Name: INO‐1001 Product Code: NA Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: 9‐[N‐ (3‐morpholinopropyl)‐aminosulfonyl]‐5,6‐dihydro‐5‐oxo‐11‐H‐indeno [1,2‐c] isoquinoline methanesulfonic acid CAS Number: NA Current Sponsor code: INO‐1001 Other descriptive name: NA Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 125 mg/250 ml ‐ Pharmaceutical form of the placebo: Intravenous infusion Route of administration of the placebo: Intravenous use Product Name: INO‐1001 Product Code: NA Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: 9‐[N‐ (3‐morpholinopropyl)‐aminosulfonyl]‐5,6‐dihydro‐5‐oxo‐11‐H‐indeno [1,2‐c] isoquinoline methanesulfonic acid CAS Number: NA Current Sponsor code: INO‐1001 Other descriptive name: NA Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 250 mg/250 ml ‐ CONDITION: INO‐1001 is being developed for the treatment of high‐risk subjects undergoing cardiopulmonary bypass (CPB) for coronary revascularization and/or valve surgery. PRIMARY OUTCOME: Main Objective: To demonstrate that intravenous INO‐1001 is safe and tolerable when administered to subjects undergoing elective CPB for coronary revascularization and/or valve surgery. ; ; To demonstrate that INO‐1001 reduces a composite endpoint of major post‐operative complications during the first 30 post‐operative days in high‐risk subjects undergoing elective CPB for coronary revascularization and/or valve surgery. Primary end point(s): The primary efficacy endpoint will be a reduction in a composite endpoint consisting of any one of the following major post‐operative complications which occur during the Treatment, Observation, or Followed‐Up Phases:; • thirty day all‐cause mortality; • prolonged mechanical ventilation, as defined by mechanical ventilatory support > seventy‐two hours following arrival in the intensive care unit / recovery room; • renal dysfunction, as defined by a need for renal replacement therapy (dialysis or CVVH); • profound cardiac failure, as defined by requirement of a left ventricular assist device or prolonged use of intravenous vasopressors or inotropic agents, as defined by usage more than forty‐eight (48) hours following arrival in the intensive care unit / recovery room Secondary Objective: To demonstrate that INO‐1001 improves post‐operative clinical outcomes and physiologic parameters during the first 30 post‐operative days in high risk subjects undergoing elective CPB for coronary revascularization and/or valve surgery.; ; Assessment of the pharmacokinetic profile of intravenous INO‐1001 administered to subjects undergoing elective CPB for coronary revascularization and/or valve surgery.; ; Assessment of the effect of intravenous INO‐1001 on cardiac biomarkers in subjects undergoing elective CPB for coronary revascularization and/or valve surgery.; INCLUSION CRITERIA: All eligible subjects must meet all of the following criteria: • Scheduled to undergo elective cardiopulmonary bypass for coronary revascularization and/or valve surgery • Written informed consent must be obtained prior to participation • Age eighteen (18) to ninety (90) years (inclusive) • Males and non‐pregnant non‐lactating femals of child‐bearing potential who agree to use two effective methods of contraception (e.g. condom and spermicide) for three (3) months following exposure to the study drug. • Third (Main) Phase ONLY: European System for Cardiac Operative Risk Evaluation (euroSCORE) equal to or greater than six calculated at any time within ninety‐six hours prior to anticipated study drug administration. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for thi