a study to evaluate efficacy and safety of qpi-1002 for prevention of acute kidney injury following cardiac surgery

Conditions: Acute Kidney Injury

Summary: this trial is designed to evaluate qpi-1002 versus placebo for the prevention of aki in subjects who are at high risk for aki following cardiac surgery. half of the participants will receive qpi-1002 while the other half will receive placebo.

this is a randomized, double-blind, placebo-controlled, phase 2 trial to evaluate qpi-1002 versus placebo for the prevention of aki in subjects who are at high risk for aki following cardiac surgery.

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.)

Keywords: aki