Platelet Transfusion for Bleeding in Children on ECMO

(ECSTATIC Trial)

No longer recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal method for administering platelet transfusions to critically ill children on ECMO, a machine that assists with breathing and heart function, to prevent bleeding. Researchers will test two strategies: one administering transfusions at a higher platelet count and another at a lower count. The goal is to reduce transfusion-related risks. Children on ECMO with no or minimal bleeding within 24 hours of starting the machine may qualify for participation. As a Phase 4 trial, the treatment has already received FDA approval and proven effective, allowing researchers to understand its benefits for more patients.

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 is the safety track record for these platelet transfusion strategies?

Studies have shown that platelet transfusions are common in children using ECMO, a machine that supports the heart and lungs. However, these transfusions carry risks. Research indicates that excessive platelet transfusions might increase the chances of complications or even death. One study found that over 97% of children on ECMO needed platelet transfusions at some point, highlighting their prevalence.

Another study suggested that reducing the number of transfusions does not affect survival rates, indicating that fewer transfusions might be just as safe as more. The evidence emphasizes the importance of finding the right balance to avoid unnecessary risks while still aiding children on ECMO. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it aims to identify the best platelet transfusion strategy for children experiencing bleeding while on ECMO (extracorporeal membrane oxygenation). Unlike the standard approach, which often involves a one-size-fits-all platelet count threshold, this trial compares two specific strategies: a higher threshold and a lower threshold for when to transfuse platelets. By tailoring platelet transfusion more precisely, the trial hopes to improve outcomes and minimize unnecessary transfusions, which can reduce potential side effects and resource use.

What evidence suggests that this trial's platelet transfusion strategies could be effective for children on ECMO?

Research has shown that platelet transfusions for children on ECMO (a machine that assists heart and lung function) can increase the risk of bleeding and death. Some studies found that children receiving more platelet transfusions had a higher chance of dying in the hospital. Observational data also suggest a link between the number of platelet transfusions and a higher risk of bleeding. In this trial, participants will be randomized into different transfusion strategies. Evidence indicates that the higher platelet transfusion strategy can lead to more issues, such as blood clots. In contrast, the lower platelet transfusion strategy aims to reduce these risks by limiting transfusions, hoping to decrease complications and improve outcomes for these critically ill children. ^{6 7 8 9 10}

Who Is on the Research Team?

Oliver Karam, MD, PhD

Principal Investigator

Yale University

Marianne Nellis, MD

Principal Investigator

NewYork-Presbyterian / Weill Cornell

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05796557

NCT05796557 | ECMO Hemostatic Transfusions in Children However, in observational studies, prophylactic platelet transfusions to children on ECMO have been independently associated with increased thrombosis, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39485885/

Analysis of platelet transfusion efficacy during ... The aim of this study was to investigate the effect of platelet transfusion during postoperative treatment with ECMO in children undergoing ...

3. journals.lww.com journals.lww.com/pccmjournal/fulltext/2024/07001/prophylactic_transfusion_strategies_in_children.4.aspx

Prophylactic Transfusion Strategies in Children Supported.. ... Observational data suggest that platelet transfusion volume may be associated with increased bleeding risk in pediatric ECMO patients (6).

4. withpower.com withpower.com/trial/phase-4-thromboembolism-6-2023-d12d6

Platelet Transfusion for Bleeding in Children on ECMO 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 ...

5. ctv.veeva.com ctv.veeva.com/study/ecmo-hemostatic-transfusions-in-children

ECMO Hemostatic Transfusions in Children (ECSTATIC) The primary outcomes will be the separation between pre-transfusion platelet counts, and the total platelet dose (in mL/kg/run). Secondary ...

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

Extracorporeal Membrane Oxygenation Patient Outcomes ... CONCLUSIONS: These data suggest that a restrictive transfusion protocol is noninferior to ECMO patient survival. Additional, prospective ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7433883/

Blood product transfusion and mortality in neonatal ... In summary, our data suggests that the rate of RBC and platelet transfusions administered during neonatal ECMO is associated with increased ...

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

Association between blood transfusion and early mortality ... Blood transfusion normalized by hospital stay emerged as a critical predictor of 90-day mortality in ECMO patients. Thus, optimizing blood ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/vox.13583

Patient‐tailored platelet transfusion practices for children ... We found that more than 97.4% of patients had a platelet count <100 × 109/L at some point during their ECMO course. Platelets were transfused ...

10. accjournal.org accjournal.org/journal/view.php?doi=10.4266/kjccm.2016.00983

Blood Transfusion Strategies in Patients Undergoing ... Their survival rate was 73.7% and the transfusion rate was 63.2%. They increased the ECMO flow rate, instead of transfusing RBCs, to keep SpO2 > ...