Platelet Transfusion for Bleeding in Children on ECMO

(ECSTATIC Trial)

Recruiting at 10 trial locations

Overseen By Oliver Karam, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Disqualifiers: Oncology, Congenital bleeding, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 21 days

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Critically ill children supported by extracorporeal membrane oxygenation (ECMO) receive large volumes of prophylactic platelet transfusions to prevent bleeding. However, mounting evidence has demonstrated significant morbidity and mortality associated with these transfusions. The ECmo hemoSTAtic Transfusions In Children (ECSTATIC) pilot trial will test two different platelet transfusion strategies, based on two different platelet counts thresholds, one high (higher platelet transfusion strategy) and one low (lower platelet transfusion strategy). The pilot will gather the necessary information to perform a full trial which will provide a better understanding of how to transfuse platelets to children supported by ECMO and reduce the associated morbidity.

Do I have to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It is best to consult with the trial coordinators for specific guidance.

What data supports the idea that Platelet Transfusion for Bleeding in Children on ECMO is an effective treatment?

The available research shows that platelet transfusions are commonly used for children on ECMO due to frequent bleeding complications. However, the studies mainly focus on describing the practice of platelet transfusion and its association with complications and mortality, rather than directly proving its effectiveness. There is no mention of alternative treatments being compared or specific data points showing improved outcomes directly linked to platelet transfusions. Therefore, while platelet transfusions are a standard practice, the research does not provide clear evidence of their effectiveness in improving outcomes for bleeding in children on ECMO. ^{1 2 3 4 5}

What safety data exists for platelet transfusion in children on ECMO?

The safety data for platelet transfusion in children on ECMO is limited. Studies indicate that bleeding is a common complication during ECMO, and platelet transfusions are often used to manage this. However, there is little information on how platelet transfusions affect ECMO oxygenator function. One study found that higher numbers of platelet transfusions were associated with increased in-hospital mortality, suggesting a need for more research to determine appropriate transfusion triggers. Another study highlighted the incidence of platelet dysfunction in children on ECMO, which could contribute to bleeding complications. Overall, more randomized controlled trials are needed to better understand the safety and efficacy of platelet transfusions in this context. ^{1 2 3 5 6}

Is platelet transfusion a promising treatment for bleeding in children on ECMO?

Platelet transfusion is a promising treatment for bleeding in children on ECMO because it is commonly used to manage bleeding, which is a major complication of ECMO. It helps to replenish platelets, which are crucial for blood clotting, and is currently the main option available for these patients. ^{1 2 3 4 7}

Research Team

Oliver Karam, MD, PhD

Principal Investigator

Yale University

Marianne Nellis, MD

Principal Investigator

NewYork-Presbyterian / Weill Cornell

Eligibility Criteria

This trial is for critically ill children on ECMO with minimal or no bleeding. They must be between 0 to <18 years old, not have been on ECMO for more than 24 hours, and without certain conditions like cancer treatment in the last six months or congenital bleeding disorders.

Inclusion Criteria

I only have minor bleeding issues.

My child is critically ill, under 18, in intensive care on ECMO, and has had no or minimal bleeding after the procedure.

Exclusion Criteria

I have received cancer treatment or a bone marrow transplant recently.

Known objection to blood transfusions

My baby was born before 37 weeks of pregnancy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive platelet transfusions based on randomized transfusion strategy (higher or lower threshold)

Up to 21 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression to severe bleeding and/or thrombosis

Up to 90 days

Periodic assessments (in-person and virtual)

Treatment Details

Interventions

• Platelet Transfusion

Trial Overview The ECSTATIC pilot trial is testing two strategies of platelet transfusions in children on ECMO: one uses a high threshold for when to give platelets, and the other a low threshold. The goal is to find out which strategy better prevents complications.

Participant Groups

Group I: Lower platelet transfusion strategy Experimental Treatment 1 Intervention

Participants randomized to this arm will be transfused if the platelet count is \< 50 x 10e9 cells/L.

Group II: Higher platelet transfusion strategy Active Control 1 Intervention

Participants randomized to this arm will be transfused if the platelet count is \< 90 x 10e9 cells/L.

Platelet Transfusion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Platelet transfusion for:

• Prevention of bleeding in critically ill children supported by ECMO
• Treatment of bleeding in critically ill children supported by ECMO

Approved in European Union as Platelet transfusion for:

• Prevention of bleeding in critically ill children supported by ECMO
• Treatment of bleeding in critically ill children supported by ECMO

Approved in Canada as Platelet transfusion for:

• Prevention of bleeding in critically ill children supported by ECMO
• Treatment of bleeding in critically ill children supported by ECMO

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Virginia Commonwealth University

Collaborator

Trials

732

Recruited

22,900,000+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Schneider Medical Children's Center, Israel

Collaborator

Trials

1

Recruited

50+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Children's Hospital and Health System Foundation, Wisconsin

Collaborator

Trials

56

Recruited

93,300+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study of 235 platelet transfusions in 55 children on ECMO, overall platelet transfusions did not significantly affect the function of the ECMO oxygenator, indicating safety in general use.

However, in children with the lowest pre-transfusion oxygenator function, platelet transfusions were linked to a significant worsening of oxygenator performance, suggesting that careful monitoring and potential adjustments in anticoagulation strategies may be needed for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Platelet Transfusions on Extracorporeal Life Support Oxygenator's Function. Chegondi, M., Vijayakumar, N., Badheka, A., et al.[2022]

In a study of 511 children undergoing extracorporeal membrane oxygenation (ECMO), 97.1% received platelet transfusions, with higher transfusion volumes linked to increased mortality risk (odds ratio 1.05 per mL/kg).

Platelet transfusion volume was also associated with higher risks of bleeding and thrombosis, indicating that while transfusions are common, they may contribute to serious complications in pediatric patients on ECMO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet Transfusion Practice and Related Outcomes in Pediatric Extracorporeal Membrane Oxygenation. Cashen, K., Dalton, H., Reeder, RW., et al.[2022]

In a study of 87 pediatric patients on ECMO, nearly half experienced major bleeding, highlighting a significant risk associated with this life-saving intervention.

The research found that platelet function decreased over time during ECMO, which may explain the increased bleeding risk; monitoring platelet markers could help predict and manage these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation. Van Den Helm, S., Yaw, HP., Letunica, N., et al.[2023]

In a study of 234 neonates on extracorporeal membrane oxygenation (ECMO), it was found that these patients received an average of 1.3 platelet transfusions per day, highlighting the high need for transfusions in this vulnerable population.

The number of platelet transfusions varied significantly based on the medical diagnosis, with neonates suffering from meconium aspiration and sepsis requiring more transfusions, and those on venoarterial (VA) ECMO needing more transfusions than those on venovenous (VV) ECMO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter analysis of platelet transfusion usage among neonates on extracorporeal membrane oxygenation. Chevuru, SC., Sola, MC., Theriaque, DW., et al.[2019]

In a study of 24 children on ECMO, severe bleeding complications occurred in 42% of cases, and the mortality rate was 54%, highlighting the serious risks associated with ECMO support.

The study found that severe platelet dysfunction was prevalent, particularly with ADP-mediated aggregation (92% affected), suggesting that monitoring platelet function could be crucial for predicting bleeding complications in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of Platelet Dysfunction by Thromboelastography-Platelet Mapping in Children Supported with ECMO: A Pilot Retrospective Study. Saini, A., Hartman, ME., Gage, BF., et al.[2022]

In a study of 188 patients on veno-arterial (VA) ECMO, those who received 4 or more platelet transfusions had a significantly higher in-hospital mortality rate (78.6%) compared to those who received no platelets (19.6%), suggesting a potential link between excessive platelet transfusion and worse outcomes.

After adjusting for various factors, receiving 4 or more platelet transfusions was associated with a 4.68 times higher risk of in-hospital mortality, indicating the need for more research to determine appropriate transfusion practices in VA ECMO patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Platelet Transfusion and In-Hospital Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation Patients. Mazzeffi, M., Rabin, J., Deatrick, K., et al.[2023]

In a multicenter study involving 419 patients on venoarterial extracorporeal membrane oxygenation (VA ECMO), 95% developed thrombocytopenia, with 45% experiencing severe cases, highlighting a higher occurrence of this condition than previously recognized.

Severe thrombocytopenia was strongly linked to the need for platelet transfusions, with an adjusted odds ratio of 31.8, which increased to 110 when considering the presence of hemorrhage, indicating a critical relationship between low platelet counts and transfusion requirements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study. Raasveld, SJ., van den Oord, C., Schenk, J., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of Platelet Transfusions on Extracorporeal Life Support Oxygenator's Function. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Platelet Transfusion Practice and Related Outcomes in Pediatric Extracorporeal Membrane Oxygenation. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Multicenter analysis of platelet transfusion usage among neonates on extracorporeal membrane oxygenation. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Incidence of Platelet Dysfunction by Thromboelastography-Platelet Mapping in Children Supported with ECMO: A Pilot Retrospective Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Platelet Transfusion and In-Hospital Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation Patients. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The interaction of thrombocytopenia, hemorrhage, and platelet transfusion in venoarterial extracorporeal membrane oxygenation: a multicenter observational study. [2023]