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

This is an interventional treatment trial for Acute Kidney Injury focused on measuring Acute Kidney Injury, AKI, Cardiac surgery Read More

Inclusion Criteria:

• Male or female and >18 years of age.

• Scheduled for a non-emergent coronary and/or valve surgery procedure requiring CPB, to include:

  • coronary artery bypass graft (CABG) alone;
  • aortic valve replacement or repair alone, with or without aortic root repair;
  • mitral, tricuspid, or pulmonic valve replacement or repair alone;
  • simultaneous replacement of several cardiac valves;
  • CABG with aortic, mitral, tricuspid, or pulmonic valve replacement or repair;
  • CABG with combined cardiac valve replacement or repair.

• Have the following risk factors for CSA-AKI:

  • eGFR ≥ 20 and < 30 ml/min/1.73m2 OR
  • eGFR ≥ 30 and < 60 ml/min/1.73m2 and ONE of the following additional risk factors (other than age ≥ 75 years) OR
  • eGFR ≥ 60 ml/min/1.73m2 and TWO of the following additional risk factors

Additional Risk Factors:

• Age ≥ 75 years;
• Combined valve & coronary surgery;
• Previous cardiac surgery with sternotomy;
• Documented NYHA Class III or IV within 1 year prior to surgery;
• Left ventricular ejection fraction (LVEF) ≤ 35% by invasive or noninvasive diagnostic cardiac imaging - echocardiography, nuclear imaging, computed tomography, magnetic resonance imaging or angiography performed within 90 days prior to surgery. (If LVEF ≤ 35% by any invasive or noninvasive imaging procedure, patient meets the risk factor.)
• Insulin-requiring diabetes;
• Non-insulin-requiring diabetes and the presence of ≥+2 proteinuria on urinalysis (medical history or dipstick);
• Preoperative anemia (hemoglobin <11g/dl for men and women).

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.