Effects of Donor-recipient Sex-matched Blood Transfusion on Patient Outcomes (SexMATTERS RCT)

March 10, 2026 updated by: Michelle Zeller

Effects of Donor-recipient Sex-matched Versus Sex-mismatched Red Blood Cell Transfusion on Outcomes in Critically Ill Adult Patients

Red blood cell (RBC) transfusions are selected based upon matching donor and recipient blood group: donor and recipient sex are not considered when selecting blood for transfusion. Hence, transfused patients can currently receive sex-matched and/or unmatched RBCs when transfusions are given. Sex-matched stem cell transplants, and some solid organ transplants, have shown that sex-matching donor to recipient improves patient outcomes. Recent exploratory studies have also suggested that patient outcomes could be improved by sex-matching for RBC transfusion. There is emerging evidence of underlying biologic mechanism(s) to support these observations. This study is designed as a randomized controlled trial and will explore the impact on patients who receive RBC transfusions from donors of the same sex ("sex-matched") compared with donors of the opposite sex ("sex-mismatched").

The trial will study adult patients admitted to the Intensive Care Unit who require an RBC transfusion. Patients will be assigned (through a process called randomization) to receive sex-matched RBCs or sex-mismatched RBCs to determine if there is a difference in mortality between those receiving matched versus mismatched RBCs. The results of this trial could have direct implications on resources, blood inventory, and RBC transfusion ordering practices.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background: Red blood cell (RBC) transfusions are selected based upon donor and recipient blood group compatibility without consideration of donor and recipient sex. Stem cell transplants, and some solid organ transplants, have shown that sex-matching donor to recipient improves patient outcomes. The Principal Investigator has completed a systematic review/meta-analysis and a 40,000 patient exploratory analysis; both showed a signal of benefit from sex-matched RBC transfusion. Biological findings to support the hypothesis that sex-matched RBC transfusions improve survival in recipients are also emerging.

Controversial results have emerged from observational studies and a randomized controlled trial (RCT) regarding recipient mortality from sex-mismatched RBC transfusions; hence, equipoise exists.

The Principal Investigator completed a multisite pilot RCT that showed feasibility for conducting a large-scale RCT and has helped to inform design for this study proposal. The goal of this research project is to develop a precision transfusion strategy based on sex-matching of blood donor and recipient to minimize adverse effects and improve patient outcomes post-transfusion.

Overall Research Question: In transfused adult patients admitted to the Intensive Care Unit (ICU), do donor-recipient sex-matched RBC transfusions result in improved mortality compared to sex-mismatched RBC transfusions?

Methods: This study is a superiority RCT with pragmatic features that will occur across participating sites in Canada.

Study population: adult patients (age≥18) who are hospitalized with admission to an eligible ICU and requiring RBC transfusion.

Intervention: donor-recipient sex-matched RBC transfusions. Comparison: donor-recipient sex-mismatched RBC transfusions.

Primary Outcome: 30 day mortality from time of randomization. Secondary Outcomes: time to death, 30 day in-hospital mortality, 90 day mortality, hemoglobin and creatinine increment, ICU and hospital lengths of stay, number/type of transfused products and cost effectiveness analysis. Subgroup analyses will consider recipient sex, age, transfusion exposure, blood type, admitting diagnosis, baseline hemoglobin/creatinine.

Expertise: The study team is uniquely positioned with extensive knowledge and expertise in transfusion medicine, research methodology, conduct of large pragmatic trials, and biostatistics. The study team will collaborate with Canadian Blood Services and experts in blood utilization, and operational modeling. This study is supported and endorsed by the Canadian Transfusion Trials Group.

Importance & Outcomes: Anemia is common in critically ill patients; as many as 90% of patients will become anemic by the third day of their ICU admission. Between 20% and 40% of critically ill patients admitted to the ICU will require RBC transfusion; each patient will receive on average 2 to 5 RBC units. The Age of Blood Evaluation (ABLE) study showed a 90 day all cause mortality rate of 35-37% in the transfused ICU population studied. The pilot study reflected similar mortality rates. If providing sex-matched transfusions can decrease mortality, this could translate to high numbers of preventable deaths given that 85 million RBC units are transfused globally each year. If this study finds that donor-recipient sex-matching saves lives, this would require changes at the level of the blood supplier to identify sex on each RBC unit, and changes at the hospital level that would incorporate sex-matching into the selection of compatible blood for each patient.

Study Type

Interventional

Enrollment (Estimated)

11082

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Michelle Zeller, Doctor of Medicine
  • Phone Number: 73928 1-905-525-9140
  • Email: zeller@mcmaster.ca

Study Contact Backup

  • Name: Bambie Levoy-Jones, Honours Bachelor of Science
  • Phone Number: 24928 1-905-525-9140
  • Email: levoyjob@mcmaster.ca

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8L 2X2
        • Recruiting
        • Hamilton General Hospital
        • Contact:
          • Andrew Shih, Doctor of Medicine
          • Phone Number: 46140 905-527-0271
          • Email: shiha@mcmaster.ca
        • Principal Investigator:
          • Andrew Shih, Doctor of Medicine
      • Kingston, Ontario, Canada, K7L 2V7
        • Not yet recruiting
        • Kingston Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Jeannie Callum, Doctor of Medicine
      • London, Ontario, Canada, N6A 5W9
        • Not yet recruiting
        • London Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Ziad Solh, Doctor of Medicine
      • Oshawa, Ontario, Canada, L1G 8A2
        • Not yet recruiting
        • Lakeridge Health Oshawa
        • Contact:
          • Karim Soliman, Doctor of Medicine
          • Phone Number: 33720 905-576-8711
          • Email: ksoliman@lh.ca
        • Principal Investigator:
          • Karim Soliman, Doctor of Medicine
      • Ottawa, Ontario, Canada, K1Y 1J8
        • Not yet recruiting
        • The Ottawa Hospital
        • Contact:
          • Shane English, Doctor of Medicine
          • Phone Number: 16405 613-737-8899
          • Email: senglish@toh.ca
        • Principal Investigator:
          • Shane English, Doctor of Medicine
      • Toronto, Ontario, Canada, M4N 3M5
        • Not yet recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Yulia Lin, Doctor of Medicine
      • Toronto, Ontario, Canada, M5G 2C4
        • Not yet recruiting
        • Toronto General Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jacob Pendergrast, Doctor of Medicine
        • Principal Investigator:
          • Nadia Gabarin, Doctor of Medicine
      • Toronto, Ontario, Canada, M5G 1X5
        • Not yet recruiting
        • Mount Sinai Hospital
        • Contact:
        • Principal Investigator:
          • Nadine Shehata, Doctor of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults (age ≥18);
  • Admission to a participating ICU;
  • Requiring RBC transfusion.

Exclusion Criteria:

  • Requirement for a specialized RBC product or unit not readily available in inventory (e.g., rare blood type, washed RBCs, complex RBC antibodies, etc.);
  • Massively bleeding patient (i.e., ≥4 units of blood ordered at one time, or Massive Hemorrhage Protocol initiated, or an urgent blood request made);
  • Sex unknown or sex other than male or female (i.e. intersex);
  • Do not have a valid Ontario Health Insurance Plan (OHIP) health card number.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sex-matched
Sex-matched red blood cell transfusion
Biological: Sex-matched red blood cell transfusions
Sex-matched red blood cell transfusions
Active Comparator: Sex-mismatched
Sex-mismatched red blood cell transfusion
Biological: Sex-mismatched red blood cell transfusions
Sex-mismatched red blood cell transfusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30 day mortality
Time Frame: From randomization to 30 days post-randomization.
Death within 30 days of randomization.
From randomization to 30 days post-randomization.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30 day in-hospital mortality
Time Frame: From randomization to 30 days post-randomization.
In-hospital death within 30 days of randomization.
From randomization to 30 days post-randomization.
90 day mortality
Time Frame: From randomization to 90 days post-randomization.
Death within 90 days of randomization.
From randomization to 90 days post-randomization.
Time to 30 day in-hospital mortality
Time Frame: From randomization to 30 days post-randomization.
Time to in-hospital death within 30 days of randomization.
From randomization to 30 days post-randomization.
Hemoglobin increment
Time Frame: From time of randomization until death or discharge from ICU; up to 90 days post randomization.
Lowest hemoglobin post-randomization during ICU admission.
From time of randomization until death or discharge from ICU; up to 90 days post randomization.
Need for renal replacement therapy
Time Frame: From time of randomization during ICU admission, until death or discharge from ICU; up to 90 days post randomization.
Need for renal replacement therapy e.g. CRRT or HD post randomization during ICU admission.
From time of randomization during ICU admission, until death or discharge from ICU; up to 90 days post randomization.
ICU/hospital length of stay
Time Frame: From randomization to 30 days post-randomization.
The number of ICU-free days over 30 days and the number of days in hospital over 30 days.
From randomization to 30 days post-randomization.
Number/type/volume/dose of transfused product
Time Frame: From randomization to 90 days post-randomization.
Total number of transfusion interventions, cumulative proportion of units received that were from a sex-mismatched donor
From randomization to 90 days post-randomization.
Transfusion reactions
Time Frame: From randomization to 30 days post-randomization.
Reactions related to RBC transfusions.
From randomization to 30 days post-randomization.
Cost effectiveness
Time Frame: From randomization to 90 days post-randomization.
Cost effectiveness measured using the incremental cost per life year saved (ICER) between sex-matched and mismatched transfusions.
From randomization to 90 days post-randomization.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Michelle Zeller

Collaborators

Canadian Institutes of Health Research (CIHR)

Investigators

  • Principal Investigator: Michelle Zeller, Doctor of Medicine, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2025

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

March 31, 2029

Study Registration Dates

First Submitted

January 27, 2025

First Submitted That Met QC Criteria

February 19, 2025

First Posted (Actual)

February 21, 2025

Study Record Updates

Last Update Posted (Actual)

March 12, 2026

Last Update Submitted That Met QC Criteria

March 10, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5080

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Aggregate data will be shared.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sex Differences

Clinical Trials on Sex-matched red blood cell transfusions

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Trinidad & Tobago

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe