Clinical trial NCT04814264: Pilot Study of Sex-matched vs. Sex-mismatched Red Blood Cell Transfusion
Official title: Pilot Study of Sex-matched vs. Sex-mismatched Red Blood Cell Transfusion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Blood Transfusion
Keywords: Blood
Transfusion
Intensive care
Sex-matched
Sex-mismatched
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2021-03-24
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentre, pilot randomized controlled trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility outcome - Missing randomization rate (%)
timeFrame: From date of study initiation at each site until date the final patient is randomized, approximately 8 months.
measure: Feasibility outcome - Recruitment compliance (%)
timeFrame: From date the first patient is randomized until 30 days after the final patient is randomized.
measure: Feasibility outcome - Protocol adherence (%)
timeFrame: From date the first patient is randomized until 30 days after the final patient is randomized.
Secondary outcomes:
Other outcomes:
measure: Data collection outcome - Ability to provide timely monthly reports
timeFrame: From date of study initiation at each site until 30 days after the final patient is randomized.
measure: Data collection outcome - Rate of post-randomization exclusions (%)
timeFrame: From date the first patient is randomized until 30 days after the final patient is randomized.
measure: Patient important clinical outcomes - In-hospital mortality (%)
timeFrame: From date the first patient is randomized until 30 days after the final patient is randomized.
measure: Patient important clinical outcomes - Time to death (days)
timeFrame: 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.
measure: Patient important clinical outcomes - Hemoglobin increment (g/L)
timeFrame: 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.
measure: Patient important clinical outcomes - Creatinine level and increment (umol/L)
timeFrame: 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.
measure: Patient important clinical outcomes - ICU/hospital length of stay (days)
timeFrame: 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.
measure: Patient important clinical outcomes - Number/type of transfused products (unit/volume)
timeFrame: 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.
measure: Patient important clinical outcomes - Number/type of transfusion reactions
timeFrame: 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.
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
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: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: McMaster University
name: Michelle Zeller, MD
role: PRINCIPAL_INVESTIGATOR
References: