Revisiting the Universal Donor: Does Exposure to O Blood Products Affect Patient Outcomes?

NCT04859218 | Recruiting DMC

• 1 other identifier: UD_3414
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In a recent analysis of a large transfusion database (Transfusion Research Utilization, Surveillance and Tracking database \[TRUST\]), the investigators found that the transfusion of ABO non-identical RBCs to group A individual was associated with an increased risk of death in-hospital compared to patients transfused with ABO identical RBCs (Red Blood Cells). Our finding was corroborated in a separate study of low birth weight neonates who received only group O RBCs (e.g., group O neonates received ABO identical RBCs but group A, B, and AB neonates received ABO non-identical RBCs). A subgroup of neonates who received ABO non-identical transfusions had higher mortality (Z. Sohl, personal communication, April 30th, 2020). Similar adverse clinical outcomes have been reported in a number of studies where patients have received ABO non-identical RBCs and/or platelets. Together, these findings raise the concern that the longstanding policy of transfusing group O non-identical RBCs and platelets may increase the risk of harm for some patients. In Hamilton, Ontario hospitals, approximately 20% of transfused patients receive ABO non-identical RBCs every year because of inventory shortages, urgent requests, and specific phenotype requirements. The negative impact of this practice could have widespread national and international implications for transfusion policy. The ability to undertake critical exploratory analyses in transfusion medicine is enabled by large research and administrative data sets that include all Hamilton hospitals. The initial finding of potential harm with ABO non-identical RBCs is hypothesis-generating and requires confirmation through external datasets and translational studies to support a biological mechanism. If confirmed, this hypothesis can then be tested in a clinical trial.

Conditions

Myelodysplastic Syndrome

Keywords

MDS; myeloid clonal disorder

Outcome Measures

Primary Outcomes (3)

• Change in the biomarkers of inflammation(C-Reactive Protein, Circulating Immune Complexes, IL-6, IL-1β, TNF-α, IL-8, CD40 Ligand)

  The biomarkers of inflammation tests that will be performed at different time points

  Baseline

• Change in the biomarkers of inflammation from baseline (C-Reactive Protein, Circulating Immune Complexes, IL-6, IL-1β, TNF-α, IL-8, CD40 Ligand)

  The biomarkers of inflammation tests that will be performed at different time points

  1 hour after transfusion

• Change in the biomarkers of inflammation from baseline (C-Reactive Protein, Circulating Immune Complexes, IL-6, IL-1β, TNF-α, IL-8, CD40 Ligand)

  The biomarkers of inflammation tests that will be performed at different time points

  12-24 hours after transfusion

Study Arms (2)

ABO non-identical transfusion

EXPERIMENTAL

All study patients will participate in the study for two consecutive transfusion episodes (a transfusion episode is defined as a clinic visit where 2 RBC units are transfused) and will receive an ABO identical product at one transfusion episode and an ABO non-identical product for the other episode. Randomization will dictate the order of the transfusion. The number of RBCs given for each study transfusion episode will be identical 2 RBC units.

Procedure: RBC transfusion

ABO identical transfusion

ACTIVE COMPARATOR

All study patients will participate in the study for two consecutive transfusion episodes (a transfusion episode is defined as a clinic visit where 2 RBC units are transfused) and will receive an ABO identical product at one transfusion episode and an ABO non-identical product for the other episode. Randomization will dictate the order of the transfusion. The number of RBCs given for each study transfusion episode will be identical 2 RBC units.

Procedure: RBC transfusion

Interventions

RBC transfusion PROCEDURE

two consecutive transfusion episodes: an ABO identical product at one transfusion episode and an ABO non-identical product for the other episode. The number of RBCs given for each study transfusion episode will be identical 2 RBC units.

ABO identical transfusion; ABO non-identical transfusion

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age
• Diagnosis of MDS (Myelodysplastic syndrome ) without leukemia (IPSS-R classified or physician indicated either low-risk or intermediate-1)
• Stable disease (as assessed by the patient's physician using MDS Stability Assessment Algorithm)
• Blood group A, B, or AB
• Requiring 2 RBC units at least every 6 weeks or less
• Receiving transfusions in an outpatient setting

You may not qualify if:

• Unable to provide informed consent
• Blood group O
• Clinical requirement for special products because of reactions (e.g. washed or volume-reduced)

Sponsors & Collaborators

• McMaster University: lead
• CBS: collaborator

Study Sites (1)

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V-1C3, Canada

RECRUITING

Related Publications (6)

• Lapierre V, Mahe C, Auperin A, Stambouli F, Oubouzar N, Tramalloni D, Benhamou E, Tiberghien P, Hartmann O. Platelet transfusion containing ABO-incompatible plasma and hepatic veno-occlusive disease after hematopoietic transplantation in young children. Transplantation. 2005 Aug 15;80(3):314-9. doi: 10.1097/01.tp.0000167758.63247.f4.

  PMID: 16082325 BACKGROUND

• Zeller 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.

  PMID: 28840943 BACKGROUND

• Pai M, Cook R, Barty R, Eikelboom J, Lee KA, Heddle N. Exposure to ABO-nonidentical blood associated with increased in-hospital mortality in patients with group A blood. Transfusion. 2016 Mar;56(3):550-7. doi: 10.1111/trf.13376. Epub 2015 Oct 15.

  PMID: 26472598 BACKGROUND

• Refaai MA, Cahill C, Masel D, Schmidt AE, Heal JM, Kirkley SA, Blumberg N. Is It Time to Reconsider the Concepts of "Universal Donor" and "ABO Compatible" Transfusions? Anesth Analg. 2018 Jun;126(6):2135-2138. doi: 10.1213/ANE.0000000000002600. No abstract available.

  PMID: 29099432 BACKGROUND

• Heal JM, Liesveld JL, Phillips GL, Blumberg N. What would Karl Landsteiner do? The ABO blood group and stem cell transplantation. Bone Marrow Transplant. 2005 Nov;36(9):747-55. doi: 10.1038/sj.bmt.1705101.

  PMID: 16044140 BACKGROUND

• Julmy F, Ammann RA, Taleghani BM, Fontana S, Hirt A, Leibundgut K. Transfusion efficacy of ABO major-mismatched platelets (PLTs) in children is inferior to that of ABO-identical PLTs. Transfusion. 2009 Jan;49(1):21-33. doi: 10.1111/j.1537-2995.2008.01914.x. Epub 2008 Sep 4.

  PMID: 18774963 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Donald Arnold

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Donald Arnold

CONTACT

905 525-9140; arnold@mcmaster.ca

Nancy Heddle

CONTACT

905 525-9140; heddlen@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Study Design A randomized crossover design will be performed at Three (3) out-patient treatment centres in Hamilton, London, and Toronto (Juravinski Hospital Cancer Centre; London Health Sciences Centre; and Sunnybrook Health Sciences Centre). Eligible patients who require at least 2 RBCs transfusions will be randomized to receive either ABO identical followed by ABO non-identical transfusion, or ABO non-identical followed by ABO identical transfusion. The outcome will be biomarkers of inflammation. The trial will be registered on ClinicalTrials.gov and approved by the Research Ethics Boards at each site.

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 26, 2021
• Study Start: October 17, 2023
• Primary Completion: July 1, 2025
• Study Completion: December 1, 2025
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)