Red Blood Cell Transfusion Strategies for ECMO Patients

(TITRE Trial)

Not currently recruiting at 23 trial locations

Overseen By Peta Alexander, MBBS

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Boston Children's Hospital

Disqualifiers: Gestational age < 37 weeks, Congenital bleeding disorders, Hemoglobinopathies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method for administering red blood cell transfusions to critically ill children on ECMO, a life-support machine that aids heart and lung function. The researchers aim to determine if using specific criteria for transfusions, such as significant bleeding or poor oxygen delivery, is more effective than the standard method based solely on blood levels. The trial will compare these two strategies to identify which one better reduces organ problems and enhances brain development over time. Children under 6 years old on ECMO for the first time, using the VA (veno-arterial) mode, may be eligible to participate. As an unphased trial, this study provides a unique opportunity to contribute to medical knowledge that could improve care for critically ill children.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this red blood cell transfusion strategy is safe for ECMO patients?

Research shows that red blood cell transfusions are usually safe for patients using ECMO, a machine that supports the heart and lungs. Studies have found that giving fewer transfusions does not significantly change survival rates for these patients, suggesting it might be safe to limit transfusions.

Another study found that the method of administering transfusions can affect patient outcomes, but the effects depend on the patient's specific condition. Generally, medical teams carefully manage transfusions to ensure adequate oxygen delivery while minimizing risks.

Although blood transfusions carry some risks, such as allergic reactions or infections, these are rare. Medical teams closely monitor patients to ensure safety. Overall, evidence suggests that when managed carefully, red blood cell transfusions are safe for ECMO patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these transfusion strategies for ECMO patients because they aim to provide more personalized care. The center-specific threshold strategy allows red blood cell transfusions based on each hospital's established practices, which can vary but generally focus on hemoglobin or hematocrit levels. The indication-based strategy goes a step further by considering additional clinical signs, such as significant bleeding or inadequate oxygen delivery, before administering a transfusion. This approach could lead to more precise and effective treatments, potentially reducing unnecessary transfusions and improving patient outcomes.

What evidence suggests that this trial's red blood cell transfusion strategies could be effective for ECMO patients?

Research has shown that blood transfusions are crucial for patients using ECMO, a machine that supports breathing and heart function. This trial will compare two red blood cell transfusion strategies. One strategy involves center-specific hemoglobin/hematocrit threshold-based transfusions, where transfusions follow each study center's standard of care. The other strategy is indication-based, where transfusions occur if specific conditions are met in addition to the center-specific thresholds. Studies have found that setting specific guidelines for transfusions can affect patient outcomes. For example, one study discovered that using fewer blood transfusions improved blood utilization and might lead to better health outcomes. Another review emphasized the importance of balancing oxygen delivery through transfusions, especially for patients on ECMO. Overall, these findings suggest that carefully managing transfusions can help reduce complications and possibly improve recovery for critically ill patients on ECMO. ^{2 5 6 7 8}

Who Is on the Research Team?

Lynn A. Sleeper, ScD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

This trial is for critically ill children under 6 years old on their first ECMO run with veno-arterial mode. It's not for kids expected to have care limitations within 48 hours, those with congenital bleeding disorders or hemoglobinopathies, non-residents of the US/Canada, or those on short-term ECMO.

Inclusion Criteria

Veno-arterial (VA) mode of ECMO

First ECMO run during the index hospitalization

I was younger than 6 years old when I received ECMO treatment.

Exclusion Criteria

I was put on ECMO at a different hospital and then moved to a trial site.

I have a blood disorder affecting my hemoglobin.

Veno-venous (VV) mode of ECMO

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive red blood cell transfusion based on indication-based or center-specific threshold strategies while on ECMO support

Up to 30 days

Daily monitoring during ECMO

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neurodevelopmental assessments

12 months

Assessments at 3, 6, 9, and 12 months post-randomization

Long-term follow-up

Participants' neurodevelopmental outcomes and health-related quality of life are assessed one year post-randomization

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Red blood cell transfusion

Trial Overview The TITRE study tests if limiting red blood cell transfusions based on specific needs (like bleeding or low tissue oxygen) is better than using set hemoglobin levels. The goal is to see if this can reduce organ dysfunction and improve neurodevelopment in these children.

How Is the Trial Designed?

Group I: Center-specific hemoglobin/hematocrit threshold-based red blood cell transfusion strategy Experimental Treatment 1 Intervention

Red blood cell transfusion will occur according to each study center's standard of care strategy, typically based on a particular hemoglobin threshold or hematocrit threshold. When hemoglobin or hematocrit decrease to the threshold, red blood cell transfusion is administered.

Group II: Indication-based red blood cell transfusion strategy Active Control 1 Intervention

Red blood cell transfusion will occur if the center-specific hemoglobin/hematocrit threshold for transfusion is met AND at least one of the following conditions is present: a) moderate or severe bleeding; b) reduced tissue oxygen delivery, defined as serum lactate \>5 mmol/L or 2 serum lactate levels \> 3 mmol/L measured 2 hours apart; or c) hemoglobin \< 8 g/dL or hematocrit \< 25%, except for neonates (age =\< 28 d) and children with single ventricle congenital heart disease (age \< 1 y) RBC transfusion for hemoglobin \< 10g/dL or hematocrit \<30% is allowed.

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

In a study of 484 patients receiving ECMO support, higher volumes of red blood cell (RBC) transfusions were linked to increased mortality risk, particularly in patients with non-cardiac conditions, where each additional 10 mL/kg/day of transfusion raised the odds of in-hospital death by 24%.

Patients requiring ECMO for cardiac and CPR indications received significantly more RBC transfusions (105 mL/kg/day and 66 mL/kg/day, respectively) compared to those with non-cardiac indications (20 mL/kg/day), suggesting that the reason for ECMO support influences transfusion needs and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Red blood cell transfusion volume and mortality among patients receiving extracorporeal membrane oxygenation. Smith, A., Hardison, D., Bridges, B., et al.[2022]

In a study of 208 patients receiving venovenous extracorporeal membrane oxygenation (ECMO), 88% received at least one red blood cell (RBC) transfusion, indicating a high transfusion rate even among nonbleeding patients.

Despite the high rate of transfusions, there were no significant differences in survival or complication rates between patients with liberal and restrictive transfusion thresholds, suggesting that the current guidelines may need reevaluation for optimal RBC transfusion practices in ECMO patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study. Raasveld, SJ., Karami, M., van den Bergh, WM., et al.[2023]

In a study of 281 patients receiving ECMO support, it was found that transfusing packed red blood cells (RBCs) when hemoglobin (HGB) levels were above 10 g/dL did not improve in-hospital survival, leading to a revised transfusion threshold of ≤10 g/dL.

Implementing this new threshold resulted in a significant reduction of 1.2 units of RBC transfusion per patient without negatively impacting mortality rates, demonstrating a successful approach to optimize transfusion practices in ECMO patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A value-based approach to optimize red blood cell transfusion in patients receiving extracorporeal membrane oxygenation. Shudo, Y., Cheng, N., He, H., et al.[2023]

In a study of 419 patients on venoarterial extracorporeal membrane oxygenation (VA ECMO), 89% received red blood cell (RBC) transfusions, with a median of eight units transfused during a median ECMO run of 5 days, indicating that transfusions are a common practice in this setting.

Factors such as lower hemoglobin levels before ECMO, longer ECMO duration, and hemorrhage were associated with increased RBC transfusions, but no significant differences in overall survival were found based on transfusion status or regimens, suggesting a need for further research on transfusion guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfusion of red blood cells in venoarterial extracorporeal membrane oxygenation: A multicenter retrospective observational cohort study. Raasveld, SJ., Karami, M., Schenk, J., et al.[2023]

In a study involving four dogs that experienced acute hemolytic transfusion reactions, two dogs died and one was euthanized due to complications likely caused by improper storage of red blood cell (RBC) products.

The investigation revealed that RBC units from two blood banks were hemolyzed after being stored incorrectly, highlighting the importance of proper storage and monitoring of blood products to prevent life-threatening transfusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro lysis and acute transfusion reactions with hemolysis caused by inappropriate storage of canine red blood cell products. Patterson, J., Rousseau, A., Kessler, RJ., et al.[2021]

A restrictive transfusion protocol, which only allows red blood cell transfusions for patients with hemoglobin levels below 6 g/dL or between 6 to 8 g/dL with specific conditions, was safely implemented in a study of 409 cardiac surgery patients across 30 centers.

The protocol resulted in excellent patient outcomes, with a low mortality rate of 0.49% and a significant portion (65.0%) of patients avoiding transfusions altogether, suggesting that this approach can effectively reduce unnecessary transfusions while maintaining safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe application of a restrictive transfusion protocol in moderate-risk patients undergoing cardiac operations. Song, HK., von Heymann, C., Jespersen, CM., et al.[2014]

In a study involving pediatric patients under 19 years old receiving extracorporeal membrane oxygenation (ECMO) across eight institutions, higher volumes of red blood cell (RBC) transfusions were linked to increased hospital mortality, with each additional 10 mL/kg/d of transfusion raising the odds of death by 9%.

Despite maintaining average hematocrit levels at 36.8%, the high RBC transfusion volume (29.4 mL/kg/d) suggests a need for further research to determine optimal transfusion thresholds to improve outcomes in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RBC Transfusion Practice in Pediatric Extracorporeal Membrane Oxygenation Support. Muszynski, JA., Reeder, RW., Hall, MW., et al.[2023]

In a study of 201 patients undergoing extracorporeal membrane oxygenation (ECMO), red blood cell transfusion was linked to a higher risk of in-intensive care unit mortality, with each additional unit increasing the odds of death by 7%.

Transfusions were also associated with increased rates of severe complications, including acute renal failure, thromboembolic events, and sepsis, suggesting that while transfusions may be necessary, they could indicate a poorer prognosis rather than directly causing these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of red blood cell transfusion and its association with prognosis in patients undergoing extracorporeal membrane oxygenation. Lo Pinto, H., Allyn, J., Persichini, R., et al.[2018]

In a study analyzing 149,052 units of transfused red blood cells (RBCs) over 5.5 years, irradiated RBCs were found to significantly increase the frequency of non-allergic transfusion reactions, with an odds ratio of 1.89.

Prolonged storage of irradiated RBCs was specifically linked to a higher incidence of these non-allergic reactions, suggesting that both irradiation and storage duration may impact the safety of RBC transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irradiation and prolonged storage of red cells are associated with increased adverse events. Chen, J., Biller, E., Losos, M., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12361832/

Red blood cell transfusion practices in extracorporeal ... Evaluating blood transfusion practices and their impact on morbidity and mortality across extracorporeal membrane oxygenation (ECMO) configurations.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10723844/

Extracorporeal Membrane Oxygenation Patient Outcomes ... To investigate the effect of a restrictive blood product utilization protocol on blood product utilization and clinical outcomes.

3. aob.amegroups.org aob.amegroups.org/article/view/6699/html

An oxygen balancing act: a narrative review of red blood cell ... To review current literature regarding red blood cell (RBC) transfusion thresholds in extracorporeal membrane oxygenation (ECMO).

4. sciencedirect.com sciencedirect.com/science/article/pii/S0147956324001365

Evaluation of staged autologous blood transfusion during ... Outcomes assessed included Hb levels, Hct, adverse events, the success rate for decannulation, the volume of allogeneic RBC transfusions, and associated costs.

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/02676591241239569

Red blood cell transfusion in veno-arterial extracorporeal ... This narrative review aims to examine the historical and current approaches of red cell transfusion in veno-arterial extracorporeal membrane ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40615231/

Red blood cell transfusion practices in extracorporeal ... Objectives: Evaluating blood transfusion practices and their impact on morbidity and mortality across extracorporeal membrane oxygenation (ECMO) ...

7. nature.com nature.com/articles/s41598-025-11702-7

Association between blood transfusion and early mortality ... Extracorporeal membrane oxygenation (ECMO) has emerged as a crucial tool in the management of acute cardiac or respiratory failure refractory to ...

8. journals.lww.com journals.lww.com/ccejournal/fulltext/2023/12000/extracorporeal_membrane_oxygenation_patient.11.aspx

Extracorporeal Membrane Oxygenation Patient Outcomes... Findings: A restrictive blood product transfusion protocol does not significantly affect survival on ECMO for patients on venoarterial ECMO, venovenous ECMO, ...