Overview

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.