Blood Transfusion Strategies During Major Surgery (TOPGUN)

The TOPGUN Trial: Threshold for Operative and Postoperative Hemoglobin Trigger for Red Blood Cell Transfusion

The goal of this randomized clinical trial is to address the uncertainty surrounding blood transfusion strategies in the operating room for adult patients undergoing major surgery. The main question it aims to answer is:

Does a higher hemoglobin threshold for blood transfusion during surgery reduce the risk of serious complications or death after surgery compared with a lower hemoglobin threshold?

Researchers will compare a liberal and a restrictive transfusion strategy during surgery and the first few hours of recovery.

Participants will be randomly assigned to one of two blood transfusion strategies. Blood transfusions will be given to maintain either a higher hemoglobin level (90-100 g/L) or a lower hemoglobin level (70-80 g/L) during surgery and while in the recovery room after surgery. Participants will also complete questionnaires about their quality of life and recovery at 30 and 90 days after surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Perioperative Red Blood Cell Transfusion
• Intervention / Treatment: Procedure: Restrictive Transfusion; Procedure: Liberal transfusion

• Study Type: Interventional
• Enrollment (Estimated): 5058
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zanna L Vanterpool, MSc; Phone Number: 71484 613-737-8899; Email: zvanterpool@ohri.ca

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital
      • Contact: Zanna L Vanterpool, MSc; Phone Number: 71484 613-737-8899; Email: zvanterpool@ohri.ca
  • Quebec
    • Montreal, Quebec, Canada
      • Centre Hospitalier de l'Université de Montréal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients, age ≥18.
• Elective or urgent surgery.
• Risk of red blood cell transfusion of at least 10 percent.
• Preoperative hemoglobin of less than 130 g/L.
• Intraoperative hemoglobin of < 100 g/L at any time during surgery.

Exclusion Criteria:

• Active major hemorrhage as indication for surgery (e.g. ruptured aneurysm, polytrauma, etc.)
• Acute coronary syndrome or myocardial infarction within the past 6 weeks.
• Cardiac surgery, lung transplantation, or liver transplantation as the indication for surgery (a history of such surgery is allowed)
• Surgery for moderate to severe (Glasgow Coma Scale (GCS) score ≤ 12) traumatic brain injury
• Sickle cell disease (sickle cell trait is allowed)
• Pregnancy or obstetrical surgery
• Patient refusal of blood products
• Inability to provide consent
• Previous randomization in the TOPGUN(-Pilot) trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Restrictive transfusion strategy; The restrictive transfusion strategy will consist of administering red blood cell transfusion when the participant's hemoglobin level is measured below 70 g/L or to maintain a hemoglobin target range of 70-80 g/L.	Procedure: Restrictive Transfusion; Red blood cell transfusion when the participant's hemoglobin level is measured below 70 g/L or to maintain a hemoglobin target range of 70-80 g/L. This strategy will be adhered to during surgery and up to 6 hours in the post-operative anesthesia care unit.
Experimental: Liberal transfusion strategy; The liberal transfusion strategy will consist of administering red blood cell transfusion when the participant's hemoglobin level is measured below 90 g/L or to maintain a hemoglobin target range of 90-100 g/L.ed to during surgery and up to 6 hours in the post-operative anesthesia care unit.	Procedure: Liberal transfusion; Red blood cell transfusion when the participant's hemoglobin level is measured below 90 g/L or to maintain a hemoglobin target range of 90-100 g/L. This strategy will be adhered to during surgery and up to 6 hours in the post-operative anesthesia care unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day overall morbidity or mortality	Overall postoperative morbidity and mortality within 30 days after surgery, assessed using the Comprehensive Complication Index (CCI). Complications will be identified using the Postoperative Morbidity Survey (POMS) and graded according to the Clavien-Dindo classification. The CCI summarizes all postoperative complications into a continuous score ranging from 0 (no complications) to 100 (death), with higher scores indicating greater postoperative morbidity.	From randomization to 30 days post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30-day individual perioperative complications	The occurrence of individual perioperative complications will be captured using the Postoperative Morbidity Survey (POMS). Complications will be categorized according to the POMS domains, including pulmonary, infectious, renal, gastrointestinal, cardiovascular, neurological, wound, hematological, and pain-related morbidity.	From randomization to 30 days post-surgery
90-day mortality	All-cause mortality within 90 days after surgery, assessed through participant follow-up and review of the medical record.	From randomization to 90 days post-surgery
Blood product transfusions (intraoperative and postoperative)	Number of and type of blood product transfusions	From randomization to 30 days post-surgery
Change in hemoglobin	Change in hemoglobin concentration from preoperative baseline through the perioperative and postoperative period, assessed using routine laboratory measurements and reported in grams per liter (g/L).	From preoperative to 30 days post-surgery
Estimated blood loss	Estimated blood loss in mL as noted in the operative report or anesthesia record	During surgery
Intensive care admission	Occurrence of admission to an intensive care unit (ICU)	From randomization to 30 days post-surgery
Post-operative length of stay	Number of days from the date of surgery to the date of discharge from the index hospitalization	From randomization to hospital discharge (up to 30 days post-surgery)
Readmission to hospital	Occurrence of readmission to a hospital	From discharge to 30 days post-surgery
Patient-reported disability	Functional status and disability will be assessed using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The WHODAS 2.0 evaluates functioning across six domains: cognition, mobility, self-care, getting along with others, life activities, and participation in society. Higher scores indicate greater disability and functional impairment.	30 and 90 days post-surgery
Patient-reported quality of life	Patient-reported health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. The EQ-5D-5L evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	30 and 90 days post-surgery
Disease-free and overall survival (participants undergoing cancer resection)	For participants undergoing cancer resection, disease-free survival and overall survival will be assessed at 3 and 5 years after surgery through review of the electronic medical record.	3 and 5 years post-surgery

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Investigators: Principal Investigator: Daniel McIsaac, MD, The Ottawa Hospital; Principal Investigator: Guillaume Martel, MD, MSc, FRCSC, FACS, Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): August 19, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2035

Study Registration Dates

• First Submitted: July 31, 2026
• First Submitted That Met QC Criteria: July 31, 2026
• First Posted (Actual): August 6, 2026

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: July 31, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Perioperative Care; Surgery; Blood Transfusion; Anesthesiology; Perioperative Complications; Cancer Outcomes
• Other Study ID Numbers: CTO 5736; 20260417-01T (Other Identifier: OHSN-REB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Coded individual participant data from this study will be made available upon reasonable request.
• IPD Sharing Time Frame: After publication

IPD Sharing Access Criteria

Qualified researchers may access coded individual participant data and relevant supporting study documents upon reasonable request. Requests must be submitted to the Principal Investigator and include a detailed research proposal.

Access will be subject to review and approval by the Study Steering Committee, institutional review boards (if applicable), and execution of a signed data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No