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

• Status: Completed
• Trial end date: 2015-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine whether THR-184 when administered around the time of cardiac surgery that requires cardiopulmonary bypass can prevent or ameliorate the development of acute kidney injury.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thrasos Innovation, Inc.

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.