Transfusion Requirements in Cardiac Surgery III (TRICS-III)

An International, Multi-centre, Randomized Controlled Trial to Assess Transfusion Thresholds in Patients Undergoing Cardiac Surgery

TRICS-III is an international, multi-centre, open-label randomized controlled trial of two commonly used transfusion strategies in high risk patients having cardiac surgery using a non-inferiority trial design.

Study Overview

• Status: Completed
• Conditions: Disorder; Heart, Functional, Postoperative, Cardiac Surgery
• Intervention / Treatment: Other: Restrictive Transfusion Strategy; Other: Liberal transfusion strategy

• Study Type: Interventional
• Enrollment (Actual): 5028
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital, Melbourne
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Malvern, Victoria, Australia, 3144
      • Cabrini Health
    • Melbourne, Victoria, Australia, 3004
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3220
      • Barwon Health (University Hospital Geelong)
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Brazil
  • Rio de Janeiro, Brazil
    • Hospital Unimed Rio (National Institute of Cardiology)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1T2
      • Kelowna General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1L7
      • Vancouver General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St Boniface Hospital
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L4
      • Saint John Regional Hospital
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1B 3X9
      • Health Sciences Centre (Memorial University)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Science Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • London, Ontario, Canada, N6G 2V4
      • London Health Sciences Center
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B1W8
      • St Michael's Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network Toronto General Hospital
  • Quebec
    • Chemin Sainte-Foy, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital Du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada
      • Centre Hospitalier de l'Université de Montréal
    • Montreal, Quebec, Canada, H3T 1E2
      • SMBD Jewish General Hospital
    • Montréal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
    • Sherbrooke, Quebec, Canada, J1G 2E8
      • Centre Hospitalier Universitaire de Sherbrooke
• China
  • Shanghai, China
    • RenJi Hospital
  • Shanghai, China, 200235
    • Shanghai Yodak Cardio-Thoracic Hospital
• Colombia
  • Bogota, Colombia
    • Fundación Clínica Shaio
  • Bogota, Colombia
    • Fundación Cardioinfantil Instituto de Cardiología
  • Bogota, Colombia
    • Clínica de Marly
  • Bogota, Colombia
    • Hospital De San Jose
  • Santander
    • Bucaramanga, Santander, Colombia
      • Instituto del Corazón de Bucaramanga
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet - Copenhagen University Hospital
• Egypt
  • Tanta, Egypt
    • Tanta University Hospital
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Giessen, Germany
    • University Hospital Giessen
• Greece
  • Volos, Greece
    • University of Thessaly
• India
  • Gujarat, India, 380054
    • SAL Hospital
  • Karnataka
    • Bangalore, Karnataka, India
      • Narayana Health
• Israel
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Centre
• Malaysia
  • Kuala Lampur, Malaysia, 50400
    • Institut Jantung Negara
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
  • Christchurch, New Zealand, 4710
    • Christchurch Hospital
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Wellington, New Zealand, 6021
    • Wellington Hospital
• Romania
  • Târgu-Mureș, Romania
    • Emergency Institute for Cardiovascular Diseases
• Singapore
  • Singapore, Singapore
    • National Heart Centre Singapore
• South Africa
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4041
      • University of KwaZulu-Natal
• Spain
  • Barcelona, Spain
    • Hospital De La Santa Creu I Sant Pau
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Valencia, Spain, 46014
    • Consorcio Hospital General Universitario de Valencia
  • Valencia, Spain, 46026
    • Instituto de Investigación Sanitaria Hospital Univ. & Politc. La Fe de Valencia
• Switzerland
  • Basel, Switzerland, 4056
    • University Hospital Basel
  • Bern, Switzerland
    • University Hospital Bern (Inselspital)
• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3202
      • Yale-New Haven Hospital
  • Maine
    • Portland, Maine, United States
      • Maine Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Durham Veterans Affairs Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 or older
• Planned cardiac surgery using cardiopulmonary bypass
• Informed consent obtained
• Preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more

Exclusion Criteria:

• Patients who are unable to receive or who refuse blood products
• Patients who are involved in a preoperative autologous pre-donation program
• Patients who are having a heart transplant or having surgery solely for an insertion of a ventricular assist device
• Pregnancy or lactation (a negative pregnancy test must be obtained prior to randomization for women of childbearing potential.)
• Patients who are unable to receive or who refuse blood products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Restrictive transfusion strategy; Restrictive transfusion strategy: patients will receive a red cell transfusion if their hemoglobin is <75 g/L (<7.5 g/dL;<4.7mmol/L) intraoperatively and/or postoperatively	Other: Restrictive Transfusion Strategy
Active Comparator: Liberal transfusion strategy; Liberal transfusion strategy: patients will receive a red cell transfusion if their hemoglobin concentration is <95 g/L (<9.5 g/dL<5.9mmol/L) intraoperatively, or postoperatively in the intensive care unit; and/or <85 g/L (< 8.5 g/dL;<5.3mmol/L) on the ward.	Other: Liberal transfusion strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite score of any one of the following: (1) all-cause mortality; (2) myocardial infarction; (3) new renal failure requiring dialysis; or (4) new focal neurological deficit	Composite score of any one of the following events occurring during the index hospitalization (from the start of surgery until hospital discharge or postoperative day 28, whichever comes first): (1) all-cause mortality; (2) myocardial infarction; (3) new renal failure requiring dialysis; or (4) new focal neurological deficit	Up to hospital discharge or postoperative day 28 (whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Time Frame
Myocardial infarction	6 months
Death	6 months
Stroke	6 months
Incidence of in-hospital all-cause mortality	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of in-hospital myocardial infarction	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of in-hospital new renal failure requiring dialysis	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of in-hospital new focal neurological deficit	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Length of stay in the ICU and hospital	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Prolonged low output state defined as the need for two or more inotropes for 24 hours or more, intra-aortic balloon pump postoperatively or ventricular assist device	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Duration of mechanical ventilation	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of infection	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Acute kidney injury (defined by Kidney Disease Improving Global Outcomes criteria)	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of gut infarction	Up to hospital discharge or postoperative day 28 (whichever occurs first)
The proportion of patients transfused and the number of blood products and hemostatic products utilized (e.g. red cells, plasma, platelets, cryoprecipitate, factor VII) (index hospitalization)	Up to hospital discharge or postoperative day 28 (whichever occurs first)
New onset dialysis (since incident surgery) status	6 months
Coronary revascularization	6 months
Health Care Utilization	6 months
Renal function, based on changes in postoperative serum creatinine	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of Seizures	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of Encephalopathy	Up to hospital discharge or postoperative day 28 (whichever occurs first)
Incidence of Delirium	Up to hospital discharge or postoperative day 28 (whichever occurs first)

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Investigators: Principal Investigator: David Mazer, MD, Unity Health Toronto; Principal Investigator: Nadine Shehata, MD, Mount Sinai Hospital; Principal Investigator: Richard Whitlock, MD, McMaster University; Principal Investigator: Dean Fergusson, MD, Ottawa Hospital Research Institute; Principal Investigator: Kevin Thorpe, MSc, University of Toronto

Publications and helpful links

General Publications

• Carson JL, Stanworth SJ, Dennis JA, Trivella M, Roubinian N, Fergusson DA, Triulzi D, Doree C, Hebert PC. Transfusion thresholds for guiding red blood cell transfusion. Cochrane Database Syst Rev. 2021 Dec 21;12(12):CD002042. doi: 10.1002/14651858.CD002042.pub5.
• Sankar A, Rotstein AJ, Teja B, Carrier FM, Belley-Cote EP, Bolliger D, Saha T, Carmona P, Sander M, Shehata N, Thorpe KE, Mazer CD. Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial. Can J Anaesth. 2022 Dec;69(12):1493-1506. doi: 10.1007/s12630-022-02319-9. Epub 2022 Sep 19.
• Mazer CD, Whitlock RP, Fergusson DA, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, Carrier FM, McGuinness S, Young PJ, Byrne K, Villar JC, Royse A, Grocott HP, Seeberger MD, Mehta C, Lellouche F, Hare GMT, Painter TW, Fremes S, Syed S, Bagshaw SM, Hwang NC, Royse C, Hall J, Dai D, Mistry N, Thorpe K, Verma S, Juni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery. N Engl J Med. 2018 Sep 27;379(13):1224-1233. doi: 10.1056/NEJMoa1808561. Epub 2018 Aug 26.
• Garg AX, Shehata N, McGuinness S, Whitlock R, Fergusson D, Wald R, Parikh C, Bagshaw SM, Khanykin B, Gregory A, Syed S, Hare GMT, Cuerden MS, Thorpe KE, Hall J, Verma S, Roshanov PS, Sontrop JM, Mazer CD. Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial. Can J Kidney Health Dis. 2018 Jan 3;5:2054358117749532. doi: 10.1177/2054358117749532. eCollection 2018.
• Shehata N, Whitlock R, Fergusson DA, Thorpe KE, MacAdams C, Grocott HP, Rubens F, Fremes S, Lellouche F, Bagshaw S, Royse A, Rosseel PM, Hare G, Medicis E, Hudson C, Belley-Cote E, Bainbridge D, Kent B, Shaw A, Byrne K, Syed S, Royse CF, McGuiness S, Hall J, Mazer CD. Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial. J Cardiothorac Vasc Anesth. 2018 Feb;32(1):121-129. doi: 10.1053/j.jvca.2017.10.036. Epub 2017 Nov 3.
• Mazer CD, Whitlock RP, Fergusson DA, Hall J, Belley-Cote E, Connolly K, Khanykin B, Gregory AJ, de Medicis E, McGuinness S, Royse A, Carrier FM, Young PJ, Villar JC, Grocott HP, Seeberger MD, Fremes S, Lellouche F, Syed S, Byrne K, Bagshaw SM, Hwang NC, Mehta C, Painter TW, Royse C, Verma S, Hare GMT, Cohen A, Thorpe KE, Juni P, Shehata N; TRICS Investigators and Perioperative Anesthesia Clinical Trials Group. Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery. N Engl J Med. 2017 Nov 30;377(22):2133-2144. doi: 10.1056/NEJMoa1711818. Epub 2017 Nov 12.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2014
• Primary Completion (Actual): April 28, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: January 20, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Actual): August 15, 2018
• Last Update Submitted That Met QC Criteria: August 14, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Transfusion
• Other Study ID Numbers: TRICSIII; 301852 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED