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

NCT02610283 | Completed Phase 2 DMC

• 1 other identifier: QRK209
• Study Type: interventional
• Target: 341
• Locations: 3 countries
• Sites: 36

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.

Conditions

Acute Kidney Injury

Keywords

AKI

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects developing AKI as defined by the AKIN criteria

  Baseline through Day 5

Secondary Outcomes (1)

• 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

  Baseline through Day 90

Study Arms (2)

QPI-1002

ACTIVE COMPARATOR

QPI-1002 Injection, single dose

Drug: QPI-1002

Placebo

PLACEBO COMPARATOR

isotonic saline

Drug: Placebo

Interventions

QPI-1002 DRUG

IV injection

QPI-1002

Placebo DRUG

isotonic saline

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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.)

Sponsors & Collaborators

• Quark Pharmaceuticals: lead

Study Sites (36)

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

River City Clinical Research

Jacksonville, Florida, 32216, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Indiana Ohio Heart

Fort Wayne, Indiana, 46804, United States

Location

St. Vincent Medical Group

Indianapolis, Indiana, 46290, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Suburban Hospital

Bethesda, Maryland, 20814, United States

Location

Mid Michigan Cardiovascular Research

Midland, Michigan, 48670, United States

Location

Cardiac & Vascular Research Center of Northern Michigan

Petoskey, Michigan, 49770, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Bryan Heart

Lincoln, Nebraska, 68506, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Lindner Research Center, The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44111, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Baylor University

Dallas, Texas, 75246, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

St. John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Z4W7, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Centre hospitalier de l'universite de Montreal

Montreal, Quebec, H2W 1T8, Canada

Location

Mcgill University Health Center - Royal Victoria Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Montreal Heart Institute

Montreal, Quebec, J0N 1P0, Canada

Location

Instiut Universitaire de Cardiologie et Pneumologie de Quebec

Québec, Quebec, G1V4G5, Canada

Location

Charité - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Klinikum der Universität zu Köln

Cologne, 50937, Germany

Location

Herzzentrum Dresden GmbH

Dresden, 01307, Germany

Location

Westdeutsches Herzzentrum Essen / Universitätsklinikum Essen

Essen, 45122, Germany

Location

Universitätsklinikum Giessen und Marburg / Standort Giessen / Zentrum für Chirurgie

Giessen, 35385, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Herzzentrum Leipzig GmbH

Leipzig, 04289, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Related Publications (1)

• 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.

  PMID: 34474590 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Elizabeth Squiers, M.D.

  Quark Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 20, 2015
• Study Start: December 1, 2015
• Primary Completion: February 1, 2018
• Study Completion: April 1, 2018
• Last Updated: January 10, 2019

Record last verified: 2018-04

Locations

US (20); CA (8); DE (8)