A Study to Evaluate Efficacy and Safety of QPI-1002 for Prevention of Acute Kidney Injury Following Cardiac Surgery

NCT ID: NCT02610283

Last Updated: 2019-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 341 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-04-30

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

QPI-1002

QPI-1002 Injection, single dose

Group Type: ACTIVE_COMPARATOR

QPI-1002

Intervention Type: DRUG

IV injection

Placebo

isotonic saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

isotonic saline

Interventions

QPI-1002

IV injection

Intervention Type: DRUG

Placebo

isotonic saline

Intervention Type: DRUG

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.)

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quark Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elizabeth Squiers, M.D.

Role: STUDY_DIRECTOR

Quark Pharmaceuticals

Locations

University of Arizona Sarver Heart Center

Tucson, Arizona, United States

University of Florida

Gainesville, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

River City Clinical Research

Jacksonville, Florida, United States

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Indiana Ohio Heart

Fort Wayne, Indiana, United States

St. Vincent Medical Group

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Suburban Hospital

Bethesda, Maryland, United States

Mid Michigan Cardiovascular Research

Midland, Michigan, United States

Cardiac & Vascular Research Center of Northern Michigan

Petoskey, Michigan, United States

Washington University

St Louis, Missouri, United States

Bryan Heart

Lincoln, Nebraska, United States

Columbia University

New York, New York, United States

Duke University

Durham, North Carolina, United States

Lindner Research Center, The Christ Hospital

Cincinnati, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Baylor University

Dallas, Texas, United States

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, United States

St. John Regional Hospital

Saint John, New Brunswick, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Centre hospitalier de l'universite de Montreal

Montreal, Quebec, Canada

Mcgill University Health Center - Royal Victoria Hospital

Montreal, Quebec, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Instiut Universitaire de Cardiologie et Pneumologie de Quebec

Québec, Quebec, Canada

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Klinikum der Universität zu Köln

Cologne, , Germany

Herzzentrum Dresden GmbH

Dresden, , Germany

Westdeutsches Herzzentrum Essen / Universitätsklinikum Essen

Essen, , Germany

Universitätsklinikum Giessen und Marburg / Standort Giessen / Zentrum für Chirurgie

Giessen, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Herzzentrum Leipzig GmbH

Leipzig, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Countries

United States; Canada; Germany

References

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.

Reference Type: DERIVED

PMID: 34474590 (View on PubMed)

Other Identifiers

QRK209

Identifier Type: -

Identifier Source: org_study_id