Clinical trial NCT02610283: A Study to Evaluate Efficacy and Safety of QPI-1002 for Prevention of Acute Kidney Injury Following Cardiac Surgery
Official title: A Randomized, Double-Blind, Placebo Controlled , Phase 2 Study to Evaluate the Efficacy and Safety of QPI-1002 for the Prevention of Acute Kidney Injury in Subjects at High Risk for AKI Following Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: AKI
Lead sponsor: Quark Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-11-20
Enrollment: 341
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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.)

Primary outcomes:
measure: Proportion of subjects developing AKI as defined by the AKIN criteria
timeFrame: Baseline through Day 5
Secondary outcomes:
measure: Proportion of subjects developing at least on of the following events: death, needing renal replacement therapy (RRT) during the 90-day post-operative period, or having a ≥ 25% reduction in SCr based eGFR at the Day 90 visit
timeFrame: Baseline through Day 90
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Sarver Heart Center
state: Arizona
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: River City Clinical Research
state: Florida
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Indiana Ohio Heart
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Medical Group
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Bethesda
country: United States
facility: Suburban Hospital
state: Maryland
city: Midland
country: United States
facility: Mid Michigan Cardiovascular Research
state: Michigan
city: Petoskey
country: United States
facility: Cardiac & Vascular Research Center of Northern Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: New York
country: United States
facility: Columbia University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Lindner Research Center, The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Dallas
country: United States
facility: Baylor University
state: Texas
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Saint John
country: Canada
facility: St. John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Mcgill University Health Center - Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Quebec City
country: Canada
facility: Instiut Universitaire de Cardiologie et Pneumologie de Quebec
state: Quebec
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH
city: Essen
country: Germany
facility: Westdeutsches Herzzentrum Essen / Universitätsklinikum Essen
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen und Marburg / Standort Giessen / Zentrum für Chirurgie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig GmbH
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Study officials:
affiliation: Quark Pharmaceuticals
name: Elizabeth Squiers, M.D.
role: STUDY_DIRECTOR
References:
citation: Thielmann M, Corteville D, Szabo G, Swaminathan M, Lamy A, Lehner LJ, Brown CD, Noiseux N, Atta MG, Squiers EC, Erlich S, Rothenstein D, Molitoris B, Mazer CD. Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study. Circulation. 2021 Oct 5;144(14):1133-1144. doi: 10.1161/CIRCULATIONAHA.120.053029. Epub 2021 Sep 3.