Clinical trial NCT06840756: Effects of Donor-recipient Sex-matched Blood Transfusion on Patient Outcomes
Official title: Effects of Donor-recipient Sex-matched Versus Sex-mismatched Red Blood Cell Transfusion on Outcomes in Critically Ill Adult Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Red Blood Cell Transfusions
Sex Differences
Health Services
Critically Ill Intensive Care Unit Patients
Hematology
Cardiovascular
Keywords: transfusions
red blood cell transfusions
sex-matched
sex-mismatched
intensive care unit
ICU
cardiovascular
circulatory
hematology
mortality
blood donor characteristics
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2025-02-21
Enrollment: 11082
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a large scale, double-blind, superiority randomized control trial (RCT).
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 30 day mortality
timeFrame: From randomization to 30 days post-randomization.
Secondary outcomes:
measure: 30 day in-hospital mortality
timeFrame: From randomization to 30 days post-randomization.
measure: 90 day mortality
timeFrame: From randomization to 90 days post-randomization.
measure: Time to 30 day in-hospital mortality
timeFrame: From randomization to 30 days post-randomization.
measure: Hemoglobin increment
timeFrame: From time of randomization until death or discharge from ICU; up to 90 days post randomization.
measure: Need for renal replacement therapy
timeFrame: From time of randomization during ICU admission, until death or discharge from ICU; up to 90 days post randomization.
measure: ICU/hospital length of stay
timeFrame: From randomization to 30 days post-randomization.
measure: Number/type/volume/dose of transfused product
timeFrame: From randomization to 90 days post-randomization.
measure: Transfusion reactions
timeFrame: From randomization to 30 days post-randomization.
measure: Cost effectiveness
timeFrame: From randomization to 90 days post-randomization.
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Michelle Zeller, Doctor of Medicine
role: PRINCIPAL_INVESTIGATOR
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