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

Early Phase 1

Completed

• Conditions: Blood Transfusion
• Interventions: Biological: Red blood cells

• Registration Number: NCT04814264
• Lead Sponsor: McMaster University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-03-16
• Study First Submitted QC: 2021-03-23
• Study First Posted: 2021-03-24
• Study Start: 2022-01-07
• Primary Completion: 2022-05-27
• Study Completion: 2023-02-28
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-14
• Last Update Posted: 2023-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 270

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sex-mismatched red blood cell transfusion	Red blood cells	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.
Sex-matched red blood cell transfusion	Red blood cells	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.

Primary Outcome Measures

Name	Time	Method
Feasibility outcome - Missing randomization rate (%)	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%.
Feasibility outcome - Protocol adherence (%)	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%.
Feasibility outcome - Recruitment compliance (%)	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%.

Trial Locations

Locations (5)

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada