QPI-1002 Phase 3 for Prevention of Major Adverse Kidney Events (MAKE) in Subjects at High Risk for AKI Following Cardiac Surgery

NCT03510897 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: QRK309
• Study Type: interventional
• Target: 1,043
• Locations: 10 countries
• Sites: 101

Brief Summary

This trial is designed to evaluate QPI-1002 versus placebo for the prevention of Major Adverse Kidney Events (MAKE) in subjects at high risk for acute kidney injury following cardiac surgery. Half of the participants will receive QPI-1002 while the other half will receive placebo.

Conditions

Cardiac Surgery

Keywords

MAKE; AKI

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects through day 90 who develop major adverse kidney events

  Baseline through day 90

Secondary Outcomes (3)

• Proportion of subjects developing AKI overall by modified AKIN criteria within 5 days post-surgery

  Baseline through day 5

• Renal function as estimated by glomerular filtration rate

  Baseline through Day 90

• Proportion of subjects who die or initiate dialysis through day 90

  Baseline through day 90

Study Arms (2)

QPI-1002

ACTIVE COMPARATOR

QPI-1002 Injection, Single dose

Drug: teprasiran

Placebo

PLACEBO COMPARATOR

isotonic saline

Drug: Placebo

Interventions

teprasiran DRUG

IV injection

Also known as: QPI-1002

QPI-1002

Placebo DRUG

isotonic saline

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥ 18 years old
• At risk for AKI following cardiac surgery on the basis of at least one of the following pre-operatively assessed risk factors:
• Reduced renal function
• Diabetes with ongoing insulin treatment
• Albuminuria
• Undergoes non-emergent open chest cavity cardiovascular surgeries, with use of cardiopulmonary bypass (CPB), with or without hypothermic circulatory arrest

You may not qualify if:

• Emergent surgeries, including aortic dissection, and major congenital heart defects
• Undergoes cardiac surgery off CPB for subjects ≥45 years old. (Cardiac surgery off CPB for subjects \<45 years old is allowed.)
• Perioperative or post cardiac surgery, an left ventricular assist device (LVAD) is inserted or anticipated

Sponsors & Collaborators

• Quark Pharmaceuticals: lead

Study Sites (104)

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35294, United States

Location

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

Cedar-Sinai Heart Institute

Los Angeles, California, 90048, United States

Location

Ronald Regan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

River City Clinical Research

Jacksonville, Florida, 32207, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Indiana/ Ohio Heart, a division of Luthern Medical Group, LLC

Fort Wayne, Indiana, 46804, United States

Location

Indiana University Health-Methodist Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Healthcare

Lexington, Kentucky, 40536, United States

Location

University of Louisville Physicians (ULP)

Louisville, Kentucky, 40202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MidMichigan Medical Center Midland

Midland, Michigan, 48670, United States

Location

Cardiac & Vascular Research Center of Northern Michigan

Petoskey, Michigan, 49770, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Bryan Heart

Lincoln, Nebraska, 68506, United States

Location

Nebraska Heart Hospital

Lincoln, Nebraska, 68526, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Saint Barnabas Medical Center

Livingston, New Jersey, 07039, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Mission Hospital, Inc.

Asheville, North Carolina, 28801, United States

Location

Duke University Hospital Medical Center

Durham, North Carolina, 27710, United States

Location

East Carolina Heart Institute at East Carolina University

Greenville, North Carolina, 27834, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Baylor Jack and Jane Hamilton Heart and Vascular Hospital - Soltero Cardiovasular

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah Health

Salt Lake City, Utah, 84132, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

University Hospital

Madison, Wisconsin, 53792, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The Prince Charles Hospital

Chermside, Qeensland, 4032, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Qeensland, 4102, Australia

Location

The Townsville Hospital

Douglas, Queensland, 4814, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St. Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Medizinische Universitat Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Kepler Universitatsklinikum GmbH

Linz, Upper Austria, 4021, Austria

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

University Hospital Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Foothills Medical Centre, Libin Cardiovascular Institute of Alberta, University of Calgary

Calgary, Alberta, T2N 2T9, Canada

Location

University of Alberta Hospital / Mazankowski Alberta Heart Institute

Edmonton, Alberta, TG6 2B7, Canada

Location

Royal Jubilee Hospital (Victoria Island Health Authority)

Victoria, British Columbia, V8R 1J8, Canada

Location

St. Boniface Hospital

Winnipeg, Manitoba, R2H2A6, Canada

Location

Horizon Health Network, Saint John Regional Hospital

Saint John, New Brunswick, E2L4L2, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L2X2, Canada

Location

London Health Sciences Center, University Hospital

London, Ontario, N6A5A5, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

Location

Centre Hospitalier de l'Universite de Montreal (CHUM)

Montreal, Quebec, H2X0C1, Canada

Location

McGill University Health Center - Royal Victoria Hospital

Montreal, Quebec, H4A3J1, Canada

Location

Institut Universitaire de cardiologie et de pneomologie de Quebec, Universite Laval

Québec, Quebec, G1V4G5, Canada

Location

Fakulni nemocnice Hradec Kralove, Kardiochirurgicka klinika

Hradec Králové, 500 05, Czechia

Location

Institut klinicke a experimenalni mediciny, Klinika kardiovaskularni chirurgie

Prague, 140 21, Czechia

Location

Fakultni nemocnice Motol a 2. LF UK, Klinika kariovaskularni chirurgie 2. LF. UK

Prague, 15006, Czechia

Location

CHU Besancon-Service de Chirurgie Thoracique et Cardiovasculaire

Besançon, 25000, France

Location

CHU - Grenoble Alpes

Grenoble, 38043, France

Location

CHU Bordeaux

Pessac, 33604, France

Location

Hospital Robert Debre

Reims, 51092, France

Location

Chu Pontchaillou Rennes

Rennes, 35000, France

Location

Hopitaux Universitaires de Strasbourg - Service de Chirurgie Cardiovasculaire

Strasbourg, 67091, France

Location

CHU Toulouse - Hospital Rangueil-Service de Chirurgie Cadriovasculaire

Toulouse, 31059, France

Location

Deutsches Herzzentrum Munchen

München, Bavaria, 80636, Germany

Location

Charite-Universitatsmedizin Berlin

Berlin, Brandenburg, 13353, Germany

Location

Klinikum der Friedrich-Schiller-Universitat Jena

Jena, Deutschland, 07747, Germany

Location

Universitatsklinikum Frankfurt am Main

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitasklinikum Giessen und Marburg GmbH

Geißen, Hesse, 35392, Germany

Location

Herz-Und Gefasszentrum Bad Bevensen

Bad Bevensen, Lower Saxony, 29549, Germany

Location

Krankenhaus der Barmherzigen Bruder Trier

Trier, Rhineland-Palatinate, 54292, Germany

Location

Herzzentrum Leipzig

Leipzig, Saxony, 04289, Germany

Location

Universitats-Herzzentrum Freiburg-Bad Krozingen

Bad Krozingen, 79189, Germany

Location

RHON-KLINIKUM Campus Bad Neustadt

Bad Neustadt an der Saale, 97616, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, 13353, Germany

Location

Universitatsklinikum Bonn

Bonn, 53127, Germany

Location

Universitatsklinikum "Carl Gustav Carus" der Technischen Universitat Dresden Klinik fur Herzchirurgle

Dresden, 01307, Germany

Location

Universitatklinicum Essen Westdeutsches Herzzentrum Essen

Essen, 45122, Germany

Location

Universitatsklinikum Heidelberg und Medizinische Fakultat

Heidelberg, 69120, Germany

Location

Universitatsklinikum Schleswig-Holstein, Campus Lubeck

Lübeck, 23538, Germany

Location

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz

Mainz, 55131, Germany

Location

Herzchirurgische Klinik und Poliklinik

München, 81377, Germany

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Waikato Hospital

Hamilton, 3204, New Zealand

Location

Wellington Regional Hospital

Wellington, 6021, New Zealand

Location

Hospital Clinico Universitario de Santiago-CHUS

Santiago de Compostela, A Coruña, 15706, Spain

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Clinic Universitario de Valencia

Valencia, 46010, Spain

Location

Royal Papworth Hospital NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0AY, United Kingdom

Location

Guy's and St Thomas Hospital

London, SE1 7EH, United Kingdom

Location

Related Publications (3)

• Scurt FG, Bose K, Mertens PR, Chatzikyrkou C, Herzog C. Cardiac Surgery-Associated Acute Kidney Injury. Kidney360. 2024 Jun 1;5(6):909-926. doi: 10.34067/KID.0000000000000466. Epub 2024 May 1.

  PMID: 38689404 DERIVED

• 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

• Hinze C, Karaiskos N, Boltengagen A, Walentin K, Redo K, Himmerkus N, Bleich M, Potter SS, Potter AS, Eckardt KU, Kocks C, Rajewsky N, Schmidt-Ott KM. Kidney Single-cell Transcriptomes Predict Spatial Corticomedullary Gene Expression and Tissue Osmolality Gradients. J Am Soc Nephrol. 2021 Feb;32(2):291-306. doi: 10.1681/ASN.2020070930. Epub 2020 Nov 25.

  PMID: 33239393 DERIVED

Study Officials

• Nitsan Halevy, MD

  Quark Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: April 18, 2018
• First Posted: April 27, 2018
• Study Start: June 29, 2018
• Primary Completion: October 14, 2020
• Study Completion: April 12, 2021
• Last Updated: July 16, 2021

Record last verified: 2021-07

Locations

DE (18); NZ (3); GB (2); BE (1); CA (12); ES (10); AU (9); FR (7); US (36); CZ (3)