Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial
Greg Knoll,
Bram Rochwerg,
François Lauzier,
Marat Slessarev,
Michaël Chasse,
Karen E A Burns,
Alexis F Turgeon,
John Gordon Boyd,
Frédérick D'Aragon,
Shane English,
Matthew Weiss,
Maureen Meade,
Sonny Dhanani,
Marie-Hélène Masse,
François-Martin Carrier,
Steven Hanna,
Andrew Healey,
Simon J W Oczkowski,
Anne-Julie Frenette,
Anique Ducharme,
Prosanto Chaudhury,
Markus Selzner,
Ruth Breau,
Mélanie Masse,
Héloïse Cardinal,
Brigitte Bolduc,
Caroline Lamarche,
Etienne Couture,
Sandra Holdsworth,
Liz Bertholz,
Heather Talbot,
Patrick Luke,
M Khaled Shamseddin,
Jeffrey Zaltzman,
Darin Treleaven
Affiliations
Greg Knoll
Department of Medicine, Division of Nephrology, University of Ottawa, Ottawa, Ontario, Canada
Bram Rochwerg
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
François Lauzier
Population Health and Optimal Health Practives Research Unit (Trauma - Emergency - Critical Care Medicine), Centre de Recherche du CHU de Québec - Université Laval, Quebec, Quebec, Canada
Marat Slessarev
Department of Medicine, Division of Critical Care, Western University, London, Ontario, Canada
Michaël Chasse
Department of Medicine, Université de Montréal, Montreal, Québec, Canada
Karen E A Burns
Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Ontario, Canada
Alexis F Turgeon
Population Health and Optimal Health Practives Research Unit (Trauma - Emergency - Critical Care Medicine), Centre de Recherche du CHU de Québec - Université Laval, Quebec, Quebec, Canada
John Gordon Boyd
Department of Critical Care Medicine, Queen’s University, Kingston, Ontario, Canada
Frédérick D'Aragon
Department of Anesthesiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Shane English
Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Matthew Weiss
Transplant Québec, Montreal, Québec, Canada
Maureen Meade
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
Sonny Dhanani
Department of Pediatrics, Division of Critical Care, Children’s Hospital of Eastern Ontario and University of Ottawa, Ottawa, Ontario, Canada
Marie-Hélène Masse
Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
François-Martin Carrier
Department of Anesthesiology, Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada
Steven Hanna
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
Andrew Healey
Department of Medicine, Division of Emergency Medicine, McMaster University, Hamilton, Ontario, Canada
Simon J W Oczkowski
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Anne-Julie Frenette
Universite de Montreal, Montreal, Québec, Canada
Anique Ducharme
Department of Medicine, Université de Montréal, Montreal, Québec, Canada
Prosanto Chaudhury
Department of Surgery and Oncology, McGill University, Montreal, Québec, Canada
Markus Selzner
Multi-Organ Transplant Program, Toronto General Hospital, Toronto, Quebec, Canada
Ruth Breau
Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
Mélanie Masse
Department of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
Héloïse Cardinal
Department of Medicine, Université de Montréal, Montreal, Québec, Canada
Brigitte Bolduc
Department of Pharmacy, Centre integre universitaire de sante et de services sociaux de l`Estrie Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
Caroline Lamarche
Department of Medicine, Université de Montréal, Montreal, Québec, Canada
Etienne Couture
Department of Anesthesiology and Critical Care, Quebec Heart & Lung Institute, Université Laval, Quebec, Quebec, Canada
Sandra Holdsworth
Canadian Donation and Transplant Research Program, Edmonton, Alberta, Canada
Liz Bertholz
Canadian Donation and Transplant Research Program, Edmonton, Alberta, Canada
Heather Talbot
Canadian Donation and Transplant Research Program, Edmonton, Alberta, Canada
Patrick Luke
Department of Surgery, Division of Urology, Western University, London, Ontario, Canada
M Khaled Shamseddin
Department of Medicine, Division of Nephrology, Queen’s University, Kingston, Ontario, Canada
Jeffrey Zaltzman
Department of Medicine, University of Toronto, Toronto, Ontario, Canada
Darin Treleaven
Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Introduction Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.Methods and analysis We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.Ethics and dissemination We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).Trial registration number NCT05148715.
