A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)

Exclusion Criteria

• •If any of the following criteria apply prior to surgery, the patient will be excluded from the study:
• •Age \> 85 years;
• •Weight \>174 kg or 383 lbs;
• •The presence of AKI (KDIGO criteria) at the time of screening ;
• •Surgery to be performed without CPB;
• •Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature \< 28°Celsius (82.4° Fahrenheit);
• •eGFR (MDRD) \<20 ml/min/1.73m2;
• •Surgery for aortic dissection;
• •Surgery to correct a major congenital heart defect (e.g., Tetralogy of Fallot, transposition of the great vessels, single ventricle, Ebsteins anomaly. Bicuspid aortic valve is not to be considered a congenital heart defect.);
• •Prior organ transplantation;
• •Dialysis-dependence;
• •Administration of iodinated contrast media within 24 hours prior to cardiac surgery;
• •If received contrast media prior to 24 hours and have AKI as defined by KDIGO criteria;
• •Cardiogenic shock or haemodynamic instability within the 24 hours prior to surgery, including the anesthesia induction period; as defined by a systolic BP \<80 mm Hg and pulse \>120 beats per minute (bpm) and requirement for inotropes or vasopressors or other mechanical devices such as intra-aortic balloon counter-pulsation (IABP);
• •Requirement for any of the following within seven (7) days prior to cardiac surgery:
• •* defibrillator or permanent pacemaker,
• •* mechanical ventilation,
• •* intra-aortic balloon counter-pulsation (IABP),
• •* left ventricular assist device (LVAD),
• •* other forms of mechanical circulatory support (MCS);
• •Cardiopulmonary resuscitation within 14 days prior to cardiac surgery;
• •Known history of cancer within the past 5 years, except for carcinoma in situ of the cervix or adequately treated basal cell carcinoma of the skin;
• •Known or suspected sepsis at time of screening;
• •Known or suspected glomerulonephritis or interstitial nephritis at time of screening;
• •Confirmed or treated endocarditis within previous 30 days prior to cardiac surgery;
• •Other current active infection requiring antibiotic treatment;
• •Patients with known active human immunodeficiency virus infection;
• •Documented history of HIV antibodies;
• •Patients with known active Hepatitis B (HBV) or Hepatitis C (HCV) infection;
• •Documented history of HCV antibodies;
• •Documented history of HBV antigens;
• •Patients on immunosuppressant drugs or prednisone over the dose of 20 mg per day;
• •Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 times the upper limit of normal (ULN) at time of screening or Child Pugh Class C liver disease ( see appendix 6) or higher;
• •Any congenital coagulation disorder;
• •Pregnancy or lactation;
• •If patient has "Do Not Resuscitate" (DNR) status;
• •Known hypersensitivity to the study drug or any of its excipients;
• •Treatment with an investigational drug or participation in an interventional trial within 60 days prior to 1st dose of study drug;
• •In the opinion of the investigator any disease processes or confounding variables that would inappropriately alter the outcome of the study;
• •Inability to comply with the requirements of the study protocol.