Clinical trial NCT02610283 (phase 2, status: completed)
Conditions: acute kidney injury
ICD codes: N26.2, Q63.0, Q63.2, Z52.4, I75.81, N19, N20.0
Drugs: qpi-1002, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Have the ability to understand the requirements of the study, are able to provide
             written informed consent and are willing and able to comply with the requirements of
             the study

          -  Male or female, age ≥ 45 years old.

          -  Have stable renal function per Investigator assessment and no known increase in serum
             creatinine of ≥ 0.3 mg/dL during preceding 4 weeks.

          -  Scheduled to undergo non-emergent open chest cavity cardiovascular surgeries,
             including use of coronary pulmonary bypass (CPB) and no CPB:

               -  Combined coronary artery bypass grafting (CABG) surgery and surgery of one or
                  more cardiac valve (valve(s) surgery) and at least 1 AKI Risk Factor;

               -  Surgery of more than one cardiac valve (valve surgery) and at least 1 AKI Risk
                  Factor;

               -  Surgery of the aortic root or ascending part of the aorta, or in combination with
                  the aortic valve, and at least 1 AKI Risk Factor; circulatory arrest is not
                  excluded;

               -  Aortic root or ascending part of the aorta, combined with CABG and/or valve(s)
                  surgery and at least 1 AKI Risk Factor; circulatory arrest is not excluded;

               -  If only CABG or single valve surgery, subjects are required to have at least 2
                  AKI Risk Factors:

        AKI Risk Factors:

          -  Age ≥ 70 years

          -  eGFR ≤ 60 ml/min/1.73m2 by CKD-EPI formula at Screening.

          -  Diabetes (Type 1 or 2), requiring at least 1 oral hypoglycemic agent or insulin

          -  Proteinuria ≥ 0.3g/d, spot UPCR ≥ 0.3g/gm or urine dip stick ≥ +2

          -  History of congestive heart failure requiring hospitalization

        Exclusion Criteria:

          -  Have an eGFR ≤ 20 mL/min/1.73 m2

          -  Subjects with an eGFR ≤ 60 mL/min/1.73 m2 requiring intravascular iodinated contrast
             within 48 hours of the day of surgery. However, subjects may be included if the post
             contrast increase in serum creatinine is < 0.3 mg/dl in at least 2 serum creatinine
             evaluations performed not less than 36 hours apart.

          -  Have a history of any organ or cellular transplant which requires active
             immunosuppressive treatment which can interfere with kidney function

          -  Emergent surgeries, including aortic dissection, and major congenital heart defects

          -  Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter
             aortic valve replacement (TAVR) or single vessel, mid-CAB off-pump surgeries or left
             ventricular assist device (LVAD) implantation

          -  Have participated in an investigational drug study in the last 30 days

          -  Have a known allergy to or had participated in a prior study with siRNA

          -  Have a history of human immunodeficiency virus (HIV) infection

          -  Have known active Hepatitis B (HBV) (Note: Subjects with a serological profile
             suggestive of clearance, or prior antiviral treatment of HBV infection may be
             enrolled)

          -  Are HCV-positive (detectable HCV RNA) (Note: Subjects at least 24 weeks from
             completion of treatment with an antiviral regimen and who remain free of HCV as
             determined by HCV RNA testing may be enrolled.)

          -  Have had cardiogenic shock or hemodynamic instability within the 24 hours prior to
             surgery, requiring inotropes or vasopressors or other mechanical devices such as
             intra-aortic balloon counter-pulsation (IABP)

          -  Have required any of the following within a week prior to cardiac surgery:
             defibrillator or permanent pacemaker, mechanical ventilation, IABP, left ventricular
             assist device (LVAD), other forms of mechanical circulatory support (MCS) (Note: The
             prophylactic insertion of an IABP preoperatively for reasons not related to existing
             LV pump function is not exclusionary).

          -  Have required cardiopulmonary resuscitation within 14 days prior to cardiac surgery

          -  Have ongoing sepsis or history of sepsis within the past 2 weeks or untreated
             diagnosed infection prior to Screening visit. Sepsis is defined as presence of a
             confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension

          -  Have total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) > 2 times the upper limit of normal (ULN) at time of screening

          -  Have Child Pugh Class A liver disease with ALT/AST above the upper limit of normal or
             Class B or higher. (This criterion is only applicable in a patient population with
             underlying chronic liver disease, i.e., cirrhosis.)