A Study of THR-184 in Patients at Risk of Developing Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI)
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury; Wounds and Injuries
Intervention: THR-184; Placebo
Intervention description: THR-184 is a synthetic oligopeptide administered intravenously.; A normal saline solution identical in appearance to the active drug solution
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 452.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Acute Kidney Injury; AKI; Cardiac surgery

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.
    

Eligibility 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.