Blood TransfusionEarly Phase 1NCT04814264
Pilot Study of Sex-matched vs. Sex-mismatched Red Blood Cell Transfusion
A Early Phase 1 study testing Red blood cells in people with Blood Transfusion, run by McMaster University at 5 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blood Transfusion
- What is being tested?
- Red blood cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 270 participants
- Where
- 5 sitesCanada
- Study dates
- 7 Jan 2022to 28 Feb 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (age ≥18)
- Admitted to the intensive care unit
- Requiring a red blood cell transfusion
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
London Health Sciences Centre
London, Ontario, N6A 5W9
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
About this study
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.
Read the 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.
- Conditions
- Blood Transfusion
- Being tested
- Red blood cells
- Keywords
- Blood, Transfusion, Intensive care, Sex-matched, Sex-mismatched
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red blood cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Sex-matched red blood cell transfusion | Experimental | 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. Receives: Biological: Red blood cells |
| Sex-mismatched red blood cell transfusion | Experimental | 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. Receives: Biological: Red blood cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility outcome - Missing randomization rate (%)
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%.
Measured: From date of study initiation at each site until date the final patient is randomized, approximately 8 months.
Feasibility outcome - Recruitment compliance (%)
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%.
Measured: From date the first patient is randomized until 30 days after the final patient is randomized.
Feasibility outcome - Protocol adherence (%)
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%.
Measured: From date the first patient is randomized until 30 days after the final patient is randomized.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2021
- Study start7 Jan 2022
- Primary completion27 May 2022
- Study completion28 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Blood TransfusionStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentre, pilot randomized controlled trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 270 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Principal investigator, Michelle Zeller, McMaster University
- Investigators
- Michelle Zeller, MD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04814264
- Sponsor's protocol ID
- Sex_MATTERS
- Status last verified
- Mar 2023
- First submitted
- 16 Mar 2021
- Last updated
- 16 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.
PubMed 38780066
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Sex-matched vs. Sex-mismatched Red Blood Cell Transfusion
- ClinicalTrials.gov ID
- NCT04814264
- Acronym / sponsor ID
- Sex_MATTERS
- Conditions
- Blood Transfusion
- Keywords
- Blood, Transfusion, Intensive care, Sex-matched, Sex-mismatched
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 270 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- 7 Jan 2022 (actual)
- Primary completion
- 27 May 2022 (actual)
- Study completion
- 28 Feb 2023 (actual)
- First posted
- 24 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicentre, pilot randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Sex-matched red blood cell transfusion | Experimental | Biological: Red blood cellsAll 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. |
| Sex-mismatched red blood cell transfusion | Experimental | Biological: Red blood cellsAll 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults (age ≥18)
- Admitted to the intensive care unit
- Requiring a red blood cell transfusion
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Red blood cellsAll transfused red blood cells will be obtained from Canadian Blood Services and will be the standard red blood cell products currently provided in Canada. | Biological | Sex-matched red blood cell transfusion, Sex-mismatched red blood cell transfusion |
Primary outcome
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%.
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%.
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%.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2023.
- Derived from this study: PubMed 38780066Radford M, Estcourt LJ, Sirotich E, Pitre T, Britto J, Watson M, Brunskill SJ, Fergusson DA, Doree C, Arnold DM. Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support. Cochrane Database Syst Rev. 2024 May 23;5(5):CD011305. doi: 10.1002/14651858.CD011305.pub3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Zeller, MD principal investigator
McMaster University
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Red blood cells in people with Blood Transfusion, run by McMaster University at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04814264, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.