Red Blood Cell TransfusionsPhase 4SexMATTERS RCTNCT06840756
Effects of Donor-recipient Sex-matched Blood Transfusion on Patient Outcomes
A Phase 4 study testing Sex-mismatched red blood cell transfusions and Sex-matched red blood cell transfusions in people with Red Blood Cell Transfusions and Sex Differences, run by Michelle Zeller at 8 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Red Blood Cell Transfusions, Sex Differences, Health Services
- What is being tested?
- Sex-mismatched red blood cell transfusions and Sex-matched red blood cell transfusions
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11,082 participants
- Where
- 8 sitesCanada
- Study dates
- 11 Sep 2025to 31 Mar 2029
- Phase
- Phase 4
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);
- Admission to a participating ICU;
- Requiring RBC transfusion.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Bambie Levoy-Jones, Honours Bachelor of Science contact
8 sites in 1 country
Canada8 sites, 8 recruiting
- Recruiting
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
Andrew Shih, Doctor of Medicine, 905-527-0271 ext. 46140, shiha@mcmaster.ca
Andrew Shih, Doctor of Medicine
- Not yet recruiting
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Jeannie Callum, Doctor of Medicine, 613-533-6000 ext. 74897, Jeannie.Callum@kingstonhsc.ca
Jeannie Callum, Doctor of Medicine
- Not yet recruiting
London Health Sciences Centre
London, Ontario, N6A 5W9
Ziad Solh, Doctor of Medicine, 1-519-685-8500 ext. 56447, Ziad.Solh@lhsc.on.ca
Ziad Solh, Doctor of Medicine
- Not yet recruiting
Lakeridge Health Oshawa
Oshawa, Ontario, L1G 8A2
Karim Soliman, Doctor of Medicine, 905-576-8711 ext. 33720, ksoliman@lh.ca
Karim Soliman, Doctor of Medicine
- Not yet recruiting
The Ottawa Hospital
Ottawa, Ontario, K1Y 1J8
Shane English, Doctor of Medicine, 613-737-8899 ext. 16405, senglish@toh.ca
Shane English, Doctor of Medicine
- Not yet recruiting
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Yulia Lin, Doctor of Medicine, 1-416-480-4042, Yulia.Lin@sunnybrook.ca
Yulia Lin, Doctor of Medicine
- Not yet recruiting
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Nadine Shehata, Doctor of Medicine, 416-586-4800 ext. 2296, Nadine.Shehata@sinaihealth.ca
Nadine Shehata, Doctor of Medicine
- Not yet recruiting
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Jacob Pendergrast, Doctor of Medicine, 1-416-340-4800 ext. 8116, Jacob.Pendergrast@uhn.ca
Nadia Gabarin, Doctor of Medicine, 416-340-4800 ext. 8116, nadia.gabarin@uhn.ca
About this study
Official title: Effects of Donor-recipient Sex-matched Versus Sex-mismatched Red Blood Cell Transfusion on Outcomes in Critically Ill Adult Patients
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.
Read the 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.
- Conditions
- Red Blood Cell Transfusions, Sex Differences, Health Services, Critically Ill Intensive Care Unit Patients, Hematology, Cardiovascular
- Being tested
- Sex-mismatched red blood cell transfusions, Sex-matched red blood cell transfusions
- Keywords
- transfusions, red blood cell transfusions, sex-matched, sex-mismatched, intensive care unit, ICU, cardiovascular, circulatory, hematology, mortality, blood donor characteristics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sex-mismatched red blood cell transfusionsBiological
Sex-mismatched red blood cell transfusions
Sex-matched red blood cell transfusionsBiological
Sex-matched red blood cell transfusions
| Study group | Role | What they receive |
|---|---|---|
| Sex-matched | Experimental | Sex-matched red blood cell transfusion Receives: Biological: Sex-matched red blood cell transfusions |
| Sex-mismatched | Active comparator | Sex-mismatched red blood cell transfusion Receives: Biological: Sex-mismatched red blood cell transfusions |
What is being measured
The primary outcome is the main question the study is designed to answer.
30 day mortality
Death within 30 days of randomization.
Measured: From randomization to 30 days post-randomization.
Secondary outcomes (9)
30 day in-hospital mortality
In-hospital death within 30 days of randomization.
Measured: From randomization to 30 days post-randomization.
90 day mortality
Death within 90 days of randomization.
Measured: From randomization to 90 days post-randomization.
Time to 30 day in-hospital mortality
Time to in-hospital death within 30 days of randomization.
Measured: From randomization to 30 days post-randomization.
Hemoglobin increment
Lowest hemoglobin post-randomization during ICU admission.
Measured: From time of randomization until death or discharge from ICU; up to 90 days post randomization.
Need for renal replacement therapy
Need for renal replacement therapy e.g. CRRT or HD post randomization during ICU admission.
Measured: From time of randomization during ICU admission, until death or discharge from ICU; up to 90 days post randomization.
ICU/hospital length of stay
The number of ICU-free days over 30 days and the number of days in hospital over 30 days.
Measured: From randomization to 30 days post-randomization.
Number/type/volume/dose of transfused product
Total number of transfusion interventions, cumulative proportion of units received that were from a sex-mismatched donor
Measured: From randomization to 90 days post-randomization.
Transfusion reactions
Reactions related to RBC transfusions.
Measured: From randomization to 30 days post-randomization.
Cost effectiveness
Cost effectiveness measured using the incremental cost per life year saved (ICER) between sex-matched and mismatched transfusions.
Measured: From randomization to 90 days post-randomization.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2025
- Study start11 Sep 2025
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (65)Papers the sponsor has linked to this study.
- Other trials for Red Blood Cell TransfusionsStudies of the same condition, open and under way.
- 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
- Phase 4
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a large scale, double-blind, superiority randomized control trial (RCT).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 11,082 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Michelle Zeller
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor-investigator, Michelle Zeller, McMaster University
- Investigators
- Michelle Zeller, Doctor of Medicine, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06840756
- Sponsor's protocol ID
- 5080
- Acronym
- SexMATTERS RCT
- Status last verified
- Mar 2026
- First submitted
- 27 Jan 2025
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregate data will be shared.
Publications
Alshalani A, van Manen L, Boshuizen M, van Bruggen R, Acker JP, Juffermans NP. The Effect of Sex-Mismatched Red Blood Cell Transfusion on Endothelial Cell Activation in Critically Ill Patients. Transfus Med Hemother. 2021 Nov 24;49(2):98-105. doi: 10.1159/000520651. eCollection 2022 Apr.
PubMed 35611381Aubron C, Nichol A, Cooper DJ, Bellomo R. Age of red blood cells and transfusion in critically ill patients. Ann Intensive Care. 2013 Jan 15;3(1):2. doi: 10.1186/2110-5820-3-2.
PubMed 23316800Zeller MP, Barty R, Aandahl A, Apelseth TO, Callum J, Dunbar NM, Elahie A, Garritsen H, Hancock H, Kutner JM, Manukian B, Mizuta S, Okuda M, Pagano MB, Poglod R, Rushford K, Selleng K, Sorensen CH, Sprogoe U, Staves J, Weiland T, Wendel S, Wood EM, van de Watering L, van Wordragen-Vlaswinkel M, Ziman A, Jan Zwaginga J, Murphy MF, Heddle NM, Yazer MH; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. An international investigation into O red blood cell unit administration in hospitals: the GRoup O Utilization Patterns (GROUP) study. Transfusion. 2017 Oct;57(10):2329-2337. doi: 10.1111/trf.14255. Epub 2017 Aug 25.
PubMed 28840943Zeller MP, Barty R, Dunbar NM, Elahie A, Flanagan P, Garritsen H, Kutner JM, Pagano MB, Poglod R, Rogers TS, Staves J, van Wordragen-Vlaswinkel M, Zwaginga JJ, Murphy MF, Heddle NM, Yazer MH; Biomedical Excellence for Safer Transfusion (BEST) Collaborative. An international investigation into AB plasma administration in hospitals: how many AB plasma units were infused? The HABSWIN study. Transfusion. 2018 Jan;58(1):151-157. doi: 10.1111/trf.14368. Epub 2017 Oct 14.
PubMed 29030954Friede T, Kieser M. Blinded sample size re-estimation in superiority and noninferiority trials: bias versus variance in variance estimation. Pharm Stat. 2013 May-Jun;12(3):141-6. doi: 10.1002/pst.1564. Epub 2013 Mar 19.
PubMed 23509095Leach Bennett J, Blajchman MA, Delage G, Fearon M, Devine D. Proceedings of a consensus conference: Risk-Based Decision Making for Blood Safety. Transfus Med Rev. 2011 Oct;25(4):267-92. doi: 10.1016/j.tmrv.2011.05.002. Epub 2011 Jul 16.
PubMed 21763103Cooper DJ, McQuilten ZK, Nichol A, Ady B, Aubron C, Bailey M, Bellomo R, Gantner D, Irving DO, Kaukonen KM, McArthur C, Murray L, Pettila V, French C; TRANSFUSE Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults. N Engl J Med. 2017 Nov 9;377(19):1858-1867. doi: 10.1056/NEJMoa1707572. Epub 2017 Sep 27.
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