ECMO Hemostatic Transfusions in Children (ECSTATIC)

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.

Study Overview

• Status: Completed
• Conditions: Hemorrhage; Thromboembolism; Extracorporeal Membrane Oxygenation Complication; Transfusion Adverse Reaction
• Intervention / Treatment: Biological: Platelet Transfusion

Detailed Description

Due to coagulopathy and thrombocytopenia induced by hemodilution and the extracorporeal circuit itself, children supported by extracorporeal membrane oxygenation (ECMO) are at significant risk of bleeding. In order to prevent bleeding, pediatric intensivists often prescribe prophylactic platelet transfusions. However, in observational studies, prophylactic platelet transfusions to children on ECMO have been independently associated with increased thrombosis, mortality, and paradoxically, increased bleeding. Guidelines to direct platelet transfusions in this patient population are limited by the lack of evidence and therefore based on expert opinion alone. Given the significant associated risks, it is crucial to provide evidence to guide clinicians.

The ECSTATIC pilot, a randomized controlled trial endorsed by BloodNet, PediECMO, the Extracorporeal Life Support Organization (ELSO), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI), will be conducted in ten sites (9 in the US and 1 in Israel). The investigators will enroll an anticipated 50 consecutive critically ill children (0 to <18 years of age), admitted to a participating pediatric, neonatal, or cardiac intensive care unit (PICU/NICU/CICU), on ECMO, and who have either no bleeding or minimal bleeding.

Non-bleeding children 0 to less than 18 years of age will be randomized 1:1 to either a platelet transfusion threshold of 90 x10e9/L (higher platelet transfusion strategy) or 50 x10e9/L (lower platelet transfusion strategy). Participants will be followed until progression to severe bleeding and/or severe thrombosis, decannulation from ECMO, or reach 21 days.

In this pilot, the investigators will test the separation between the lower and higher transfusion strategies. The primary outcomes will be the separation between pre-transfusion platelet counts, and the total platelet dose (in mL/kg/run). Secondary outcomes will be feasibility of patient enrollment and ability for an adjudication committee to determine the severity of bleeding and thrombotic outcomes.

The purpose of this pilot study is to determine the feasibility of the transfusion strategies, intervention parameters, subject availability, and other information regarding outcomes that are essential to complete the design of a large randomized controlled trial.

The large future trial will evaluate the efficacy of the two transfusion strategies, in terms of progression to severe bleeding and/or severe thrombosis. To adequately calculate the sample size, the investigators need to know the difference between the pre-transfusion platelet counts, the screening and inclusion rates, the proportion of patients who are consented within the first 24 hours after cannulation, the proportion of transfusions that are compliant with each arm's strategy, and the number of temporary suspensions.

The proposed pilot trial is innovative in that it is focused on children supported by ECMO, a population in whom transfusion strategies have never been tested previously; it involves the largest separation between the two arms of any platelet transfusion trial conducted in the past; and it involves two newly developed definitions of bleeding and thrombosis particularly applicable to children supported by ECMO.

The pilot trial will provide necessary and sufficient information to proceed with the definitive ECSTATIC Randomized Controlled Trial (RCT) to evaluate the impact of a lower prophylactic platelet transfusion threshold on the clinical outcomes in children on ECMO. ECSTATIC has the potential to optimize efficacy, to reduce platelet transfusion exposure and to decrease mortality and morbidity of these extremely ill infants and children.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Petach Tikva, Israel, 49504
    • Schneider Children's Medical Center
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Emory
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Health Care
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital of New York Presbyterian
    • New York, New York, United States, 10065
      • Komansky Children's Hospital of New York Presbyterian
    • Rochester, New York, United States, 14642
      • Golisano Children's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University School of Medicine
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Children's Hospital of Richmond at VCU
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Critically ill children (0 to <18 years of age)
• Admitted to a participating pediatric, neonatal, or cardiac intensive care unite (PICU/NICU/CICU)
• On extracorporeal Membrane Oxygenation (ECMO)

• Who have either no bleeding or minimal bleeding, within 24 hours of cannulation. Minimal bleeding is defined as:

  • streaks of blood in endotracheal tube or during suctioning only
  • streaks of blood in nasogastric tube
  • macroscopic hematuria
  • subcutaneous bleeding (including hematoma and petechiae) < 5 cm in diameter
  • quantifiable bleeding < 1mL/kg/hr (e.g., chest tube)
  • bloody dressings required to be changed no more often than each 6hr, or weighing no more than 1mL/kg/hr if weighed, due to slow saturation

Exclusion Criteria:

• Post-conception age < 37 weeks at time of screening
• Underlying oncologic diagnosis (defined as receipt of chemotherapy or radiation in the last six months) or recipient of bone marrow transplant in the last year
• Congenital bleeding disorder
• Pregnant or admitted post-partum
• Decision to withdraw or withhold some critical care or interventions
• Known objection to blood transfusions
• On ECMO for > 24 hours at time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Higher platelet transfusion strategy; Participants randomized to this arm will be transfused if the platelet count is < 90 x 10e9 cells/L.	Biological: Platelet Transfusion; Participants will be transfused according to the assigned threshold for each group, with a transfusion dose of 10 mL/kg, up to one adult unit.
Experimental: Lower platelet transfusion strategy; Participants randomized to this arm will be transfused if the platelet count is < 50 x 10e9 cells/L.	Biological: Platelet Transfusion; Participants will be transfused according to the assigned threshold for each group, with a transfusion dose of 10 mL/kg, up to one adult unit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Platelet Transfusion Dose	The total dose (in mL/kg/day) will be computed by the research team, by dividing the total platelet transfusion volume by the patient's weight at admission and the number of days of intervention.	up to day 21
Pre-transfusion Platelet Count	Pre-transfusion platelet count, during intervention	During intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility Assessed by the Screening Rate	Feasibility will be assessed by the number of eligible participants that were screened.	At screening
Feasibility Assessed by the Inclusion Rate	Feasibility will be assessed by the number of eligible participants that were enrolled.	At screening
Feasibility Assessed by the Number of Informed Consents Signed in the First 24 Hours Post Cannulation.	Feasibility will be assessed by the number of participants that sign consent within the first 24 hours after ECMO cannulation.	At screening
Compliance With Transfusion Thresholds	The proportion of transfusions that were given for platelet counts below the arm threshold will be computed to assess compliance.	up to Day 21
Participants With at Least One Temporary Suspension	The number of participants who required at least one temporary suspension during ECMO.	up to Day 21
Duration for Temporary Suspensions	The investigators will collect information on the duration of each suspension.	up to Day 21
Progression to Composite Outcome of Severe Bleeding and/or Severe Thrombotic Event	The investigators will collect the proportion of participants who progress to a composite outcome of severe bleeding and/or severe thrombosis. The outcome will be adjudicated by an external review committee, blinded to the allocation arm.	up to Day 21
Number of Participants Who Were Withdrawn and/or Lost to Follow-up	Number of patients who withdraw from the study and/or are lost to follow-up (i.e., withdraw and/or are missing 90-day mortality assessment)	Up to 90 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Columbia University; University of Iowa; Emory University; Duke University; Weill Medical College of Cornell University; University of Utah; Virginia Commonwealth University; University of Rochester; Children's Hospital and Health System Foundation, Wisconsin; Johns Hopkins All Children's Hospital; Schneider Medical Children's Center, Israel
• Investigators: Principal Investigator: Oliver Karam, MD, PhD, Yale University; Principal Investigator: Marianne Nellis, MD, MS, NewYork-Presbyterian / Weill Cornell

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Actual): January 2, 2025
• Study Completion (Actual): March 25, 2025

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: ECMO; Mortality; Bleeding; Clotting; Platelet transfusion
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Embolism and Thrombosis; Thromboembolism; Hemorrhage
• Other Study ID Numbers: 2000034604; 1R34HL159119-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The proposed research will include data from 50 critically ill subjects who are on extracorporeal life support (ECMO) enrolled at ten participating sites. The final dataset will include demographic and medical information, as well as laboratory data.

After the investigators' proposed research is complete, each participating site will destroy the key linking this data to protected health information (PHI). Thus, the data will then be completely de-identified. However, the investigators believe that there remains the possibility of deductive disclosure of subjects with unusual characteristics, considering the variety of rare conditions leading to ECMO.

• IPD Sharing Time Frame: The investigators reserve the right to embargo the data for as long as two years after completion of the project (i.e. fall 2027) in order to allow the investigators' research team to publish additional observations from the data.
• IPD Sharing Access Criteria: The investigators will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; and (3) a commitment to destroying the data after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No