Clinical trial NCT03510897: QPI-1002 Phase 3 for Prevention of Major Adverse Kidney Events (MAKE) in Subjects at High Risk for AKI Following Cardiac Surgery
Official title: A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of QPI-1002 for the Prevention of Major Adverse Kidney Events (MAKE) in Subjects at High Risk for Acute Kidney Injury (AKI) Following Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cardiac Surgery
Keywords: MAKE
AKI
Lead sponsor: Quark Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-04-27
Enrollment: 1043
Sex: ALL
Minimum age (years): 18
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 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.

Detailed description: This is a randomized, double-blind, placebo-controlled, Phase 3 trial to evaluate QPI-1002 versus placebo for the prevention of Major Adverse Kidney Events in subjects at high risk for acute kidney injury following cardiac surgery. Subjects will be dosed with active drug or placebo after the completion of cardiovascular surgery.

Eligibility criteria: Key Inclusion Criteria:

* 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

Key Exclusion Criteria:

* 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

Primary outcomes:
measure: Proportion of subjects through day 90 who develop major adverse kidney events
timeFrame: Baseline through day 90
Secondary outcomes:
measure: Proportion of subjects developing AKI overall by modified AKIN criteria within 5 days post-surgery
timeFrame: Baseline through day 5
measure: Renal function as estimated by glomerular filtration rate
timeFrame: Baseline through Day 90
measure: Proportion of subjects who die or initiate dialysis through day 90
timeFrame: Baseline through day 90
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Hospital
state: Alabama
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: Cedar-Sinai Heart Institute
state: California
city: Los Angeles
country: United States
facility: Ronald Regan UCLA Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Jacksonville
country: United States
facility: River City Clinical Research
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: Fort Wayne
country: United States
facility: Indiana/ Ohio Heart, a division of Luthern Medical Group, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health-Methodist Hospital
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Physicians (ULP)
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Midland
country: United States
facility: MidMichigan Medical Center Midland
state: Michigan
city: Petoskey
country: United States
facility: Cardiac & Vascular Research Center of Northern Michigan
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital of Kansas City
state: Missouri
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Lincoln
country: United States
facility: Nebraska Heart Hospital
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Livingston
country: United States
facility: Saint Barnabas Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Asheville
country: United States
facility: Mission Hospital, Inc.
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina Heart Institute at East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor Jack and Jane Hamilton Heart and Vascular Hospital - Soltero Cardiovasular
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Madison
country: United States
facility: University Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Qeensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Qeensland
city: Douglas
country: Australia
facility: The Townsville Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital Melbourne
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universitat Innsbruck
state: Tyrol
city: Linz
country: Austria
facility: Kepler Universitatsklinikum GmbH
state: Upper Austria
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Leuven
country: Belgium
facility: University Hospital Leuven, Campus Gasthuisberg
city: Calgary
country: Canada
facility: Foothills Medical Centre, Libin Cardiovascular Institute of Alberta, University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital / Mazankowski Alberta Heart Institute
state: Alberta
city: Victoria
country: Canada
facility: Royal Jubilee Hospital (Victoria Island Health Authority)
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Saint John
country: Canada
facility: Horizon Health Network, Saint John Regional Hospital
state: New Brunswick
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Center, University Hospital
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 (CHUM)
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Center - Royal Victoria Hospital
state: Quebec
city: Québec
country: Canada
facility: Institut Universitaire de cardiologie et de pneomologie de Quebec, Universite Laval
state: Quebec
city: Hradec Králové
country: Czechia
facility: Fakulni nemocnice Hradec Kralove, Kardiochirurgicka klinika
city: Praha 4
country: Czechia
facility: Institut klinicke a experimenalni mediciny, Klinika kardiovaskularni chirurgie
city: Praha 5
country: Czechia
facility: Fakultni nemocnice Motol a 2. LF UK, Klinika kariovaskularni chirurgie 2. LF. UK
city: Besançon
country: France
facility: CHU Besancon-Service de Chirurgie Thoracique et Cardiovasculaire
city: Grenoble Cedex 9
country: France
facility: CHU - Grenoble Alpes
city: Pessac Cedex
country: France
facility: CHU Bordeaux
city: Reims
country: France
facility: Hospital Robert Debre
city: Rennes
country: France
facility: Chu Pontchaillou Rennes
city: Strasbourg Cedex
country: France
facility: Hopitaux Universitaires de Strasbourg - Service de Chirurgie Cardiovasculaire
city: Toulouse
country: France
facility: CHU Toulouse - Hospital Rangueil-Service de Chirurgie Cadriovasculaire
city: München
country: Germany
facility: Deutsches Herzzentrum Munchen
state: Bavaria
city: Berlin
country: Germany
facility: Charite-Universitatsmedizin Berlin
state: Brandenburg
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller-Universitat Jena
state: Deutschland
city: Frankfurt am main
country: Germany
facility: Universitatsklinikum Frankfurt am Main
state: Hesse
city: Geißen
country: Germany
facility: Universitasklinikum Giessen und Marburg GmbH
state: Hesse
city: Bad Bevensen
country: Germany
facility: Herz-Und Gefasszentrum Bad Bevensen
state: Lower Saxony
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Bruder Trier
state: Rhineland-Palatinate
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
state: Saxony
city: Bad Krozingen
country: Germany
facility: Universitats-Herzzentrum Freiburg-Bad Krozingen
city: Bad Neustadt An Der Saale
country: Germany
facility: RHON-KLINIKUM Campus Bad Neustadt
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Dresden
country: Germany
facility: Universitatsklinikum "Carl Gustav Carus" der Technischen Universitat Dresden Klinik fur Herzchirurgle
city: Essen
country: Germany
facility: Universitatklinicum Essen Westdeutsches Herzzentrum Essen
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg und Medizinische Fakultat
city: Lubeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein, Campus Lubeck
city: Mainz
country: Germany
facility: Universitatsmedizin der Johannes Gutenberg-Universitat Mainz
city: München
country: Germany
facility: Herzchirurgische Klinik und Poliklinik
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: Wellington Regional Hospital
city: Santiago De Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago-CHUS
state: A Coruña
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
state: Barcelona
city: L'Hospitalet De Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
state: Cordoba
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
state: Navarra
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Valencia
country: Spain
facility: Hospital Clinic Universitario de Valencia
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital NHS Foundation Trust
state: Cambridgeshire
city: London
country: United Kingdom
facility: Guy's and St Thomas Hospital
Study officials:
affiliation: Quark Pharmaceuticals
name: Nitsan Halevy, MD
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.
citation: 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.