Pilot Study of Sex-matched vs. Sex-mismatched Red Blood Cell Transfusion

March 14, 2023 updated by: Michelle Zeller, McMaster University
Blood transfusion is common for patients in hospital, especially for those in intensive care. Patients receive blood that is matched to them based on their blood group (A, B, AB, O), but not based on sex. This means male or female patients may receive male or female blood. There is some evidence to suggest that giving male patients female blood and female patients male blood (sex-mismatched blood) may be harmful. The investigators think giving males only male blood and females only female blood (sex-matched blood) will be better for the patients and improve their survival. To test this, the study team will randomly give 50% of intensive care patients who require blood only sex-mismatched blood and 50% of intensive care patients only sex-matched blood for their entire hospital stay. Then, health data of patients will be collected to see if either group does better after transfusion. Before this is done as a large study with thousands of patients, it will be attempted as a smaller pilot study with a few hundred patients to be sure the processes suggested make sense and are possible for hospitals and for the blood supplier to follow.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Blood transfusion is one of the most common procedures performed during hospitalization. Approximately 85 million red blood cell (RBC) units are transfused globally each year. RBC units are matched for blood groups but matching for other donor characteristics such as sex, is not considered. By the current standard of care, female or male patients can receive RBCs from male or female donors. However, accumulating data suggests that sex-mismatched transfusions may be harmful.

Sex-mismatched transfusions and transplantations have been associated with poor outcomes. Plasma from female donors is associated with an increased risk of transfusion related acute lung injury (TRALI); sex-mismatched heart transplantation is associated with increased transplant-associated mortality; and stem cell transplants from female donors are associated with worse outcomes.

Anemia is common during critical illness and 20-40% of critically ill patients require a mean of two to five RBC units during admission to the intensive care unit (ICU). Once a patient receives more than six RBC units, virtually all patients (>97%) will have received at least one sex-mismatched RBC. The population of transfused ICU adult patients is already at high risk of death, with a demonstrated 90-day all-cause mortality of 35-37% based on the ABLE study, and in-hospital mortality of 24-34% (institutional data). Thus, new supportive care strategies are needed to improve outcomes of this highly vulnerable patient group.

Transfusion data linked to donor sex spanning a 6-year period was previously analyzed. Using a careful analysis that controlled for covariates and stratified on time-dependent and fixed variables, 25,219 transfusion recipients were retrospectively analyzed and a significant association between male to female RBC transfusions and death [hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.02-1.69] was found. A trend towards higher mortality was also noted with female to male RBCs (HR 1.13: 95% CI 0.92-1.39), and with sex-mismatched vs. sex-matched RBCs overall (HR 1.23: 95% CI 1.04-1.45). These findings suggest that matching RBC transfusions for sex can reduce mortality in ICU patients.

The investigators hypothesize that donor-recipient sex-matched RBC transfusions are associated with improved survival in hospital compared to sex-mismatched RBC transfusions. Sex-matched RBC transfusions may represent an important, readily implementable advance in supportive care of critically ill patients.

Study Type

Interventional

Enrollment (Actual)

270

Phase

  • Early Phase 1

Contacts and Locations

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

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 4A6
        • St. Joseph's Healthcare Hamilton
      • Hamilton, Ontario, Canada, L8L 2X2
        • Hamilton General Hospital
      • Kingston, Ontario, Canada, K7L 2V7
        • Kingston Health Sciences Centre
      • London, Ontario, Canada, N6A 5W9
        • London Health Sciences Centre
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adults (age ≥18)
  • Admitted to the intensive care unit
  • Requiring a red blood cell transfusion

Exclusion Criteria:

  • Requiring a specific red blood cell unit or unit not readily available (e.g., phenotypically matched, rare blood, washed, complex red blood cell antibodies, etc.)
  • Massively bleeding (i.e. ≥4 units of blood ordered, or Massive Hemorrhage Protocol initiated, or an urgent blood request made)
  • Biological sex unknown

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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sex-matched red blood cell transfusion
All patients will receive red blood cells (RBCs) that are ABO and Rh compatible as per routine blood bank practices. In addition to routine compatibility, subjects in this arm will receive blood that is matched to their sex (donor and recipient sex are the same). Patients in this arm will receive RBCs matched to their sex until discharge from hospital or death.
Biological: Red blood cells
All transfused red blood cells will be obtained from Canadian Blood Services and will be the standard red blood cell products currently provided in Canada.
Experimental: Sex-mismatched red blood cell transfusion
All patients will receive red blood cells (RBCs) that are ABO and Rh compatible as per routine blood bank practices. In addition to routine compatibility, subjects in this arm will receive blood that is not matched to their sex (donor and recipient sex are not the same). Patients in this arm will receive RBCs mismatched to their sex until discharge from hospital or death.
Biological: Red blood cells
All transfused red blood cells will be obtained from Canadian Blood Services and will be the standard red blood cell products currently provided in Canada.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility outcome - Missing randomization rate (%)
Time Frame: From date of study initiation at each site until date the final patient is randomized, approximately 8 months.
Feasibility of randomizing consecutive eligible patients in the intensive care unit who require blood transfusion. Data collected electronically at monthly intervals. Missing randomization rate calculated by taking the number of eligible patients not randomized divided by the total number of eligible patients × 100%.
From date of study initiation at each site until date the final patient is randomized, approximately 8 months.
Feasibility outcome - Recruitment compliance (%)
Time Frame: From date the first patient is randomized until 30 days after the final patient is randomized.
Number of recruitments that are compliant out of all randomizations. Reasons for recruitment non-compliance include: (a) duplicate randomization; (b) entering incorrect identification number into the randomization program; (c) patient randomized not admitted to ICU; and, (d) randomized ICU patients not transfused. Data collected electronically at monthly intervals. Frequency of recruitment compliance calculated by taking the number of recruitments that are compliant divided by the total number of patients randomized ×100%.
From date the first patient is randomized until 30 days after the final patient is randomized.
Feasibility outcome - Protocol adherence (%)
Time Frame: From date the first patient is randomized until 30 days after the final patient is randomized.
The proportion of patients in the intervention arms who receive all red blood cell transfusions as sex-matched/sex-mismatched out of all transfused per intervention arm. Data collected electronically at monthly intervals. Percentage protocol adherence rate calculated by taking the number of patients in the intervention arm who receive all RBC transfusions as sex-matched or mismatched divided by the total number of transfused patients in the intervention arm x 100%.
From date the first patient is randomized until 30 days after the final patient is randomized.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Data collection outcome - Ability to provide timely monthly reports
Time Frame: From date of study initiation at each site until 30 days after the final patient is randomized.
Ability of each participating site to provide timely monthly reports to monitor inventory levels and mortality outcomes.
From date of study initiation at each site until 30 days after the final patient is randomized.
Data collection outcome - Rate of post-randomization exclusions (%)
Time Frame: From date the first patient is randomized until 30 days after the final patient is randomized.
Rate of post-randomization exclusions calculated by taking the number of patient exclusions post randomization divided by the total number randomized x 100%.
From date the first patient is randomized until 30 days after the final patient is randomized.
Patient important clinical outcomes - In-hospital mortality (%)
Time Frame: From date the first patient is randomized until 30 days after the final patient is randomized.
In-hospital mortality calculated by taking the number of deaths in hospital divided by the total number randomized x 100%.
From date the first patient is randomized until 30 days after the final patient is randomized.
Patient important clinical outcomes - Time to death (days)
Time Frame: From date of patient randomization until the date of death from any cause while in hospital, assessed up to 30 days after the final patient is randomized.
Time to death in days, only applicable to patients who die while in hospital.
From date of patient randomization until the date of death from any cause while in hospital, assessed up to 30 days after the final patient is randomized.
Patient important clinical outcomes - Hemoglobin increment (g/L)
Time Frame: From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Hemoglobin increment calculated by taking the post-transfusion hemoglobin value minus the pre-transfusion hemoglobin value.
From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Patient important clinical outcomes - Creatinine level and increment (umol/L)
Time Frame: From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Creatinine increment calculated by taking the post-transfusion creatinine value minus the pre-transfusion creatinine value.
From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Patient important clinical outcomes - ICU/hospital length of stay (days)
Time Frame: From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Days admitted to ICU and/or hospital.
From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Patient important clinical outcomes - Number/type of transfused products (unit/volume)
Time Frame: From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Number of units and/or volume and type of blood products/plasma derivatives transfused.
From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Patient important clinical outcomes - Number/type of transfusion reactions
Time Frame: From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.
Number and type of transfusion reactions reported.
From date of patient randomization until the date of discharge from hospital or date of death from any cause, whichever comes first, assessed up to 30 days after the final patient is randomized.

Collaborators and Investigators

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

Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)

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)

January 7, 2022

Primary Completion (Actual)

May 27, 2022

Study Completion (Actual)

February 28, 2023

Study Registration Dates

First Submitted

March 16, 2021

First Submitted That Met QC Criteria

March 23, 2021

First Posted (Actual)

March 24, 2021

Study Record Updates

Last Update Posted (Actual)

March 16, 2023

Last Update Submitted That Met QC Criteria

March 14, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • Sex_MATTERS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

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