Clinical Drug Experience Knowledgebase

Criteria

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.