ECMO Hemostatic Transfusions in Children

NCT ID: NCT05796557

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-12
• Study Completion Date: 2025-03-25

Brief Summary

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.

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.

Conditions

Extracorporeal Membrane Oxygenation Complication; Hemorrhage; Thromboembolism; Transfusion Adverse Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Higher platelet transfusion strategy

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

Group Type: ACTIVE_COMPARATOR

Platelet Transfusion

Intervention Type: BIOLOGICAL

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.

Lower platelet transfusion strategy

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

Group Type: EXPERIMENTAL

Platelet Transfusion

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: collaborator

Children's Hospital and Health System Foundation, Wisconsin

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

Johns Hopkins All Children's Hospital

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Schneider Medical Children's Center, Israel

UNKNOWN

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Oliver Karam, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Marianne Nellis, MD, MS

Role: PRINCIPAL_INVESTIGATOR

NewYork-Presbyterian / Weill Cornell

Locations

Children's Healthcare of Atlanta - Emory

Atlanta, Georgia, United States

University of Iowa Health Care

Iowa City, Iowa, United States

Norton Children's Hospital

Louisville, Kentucky, United States

Morgan Stanley Children's Hospital of New York Presbyterian

New York, New York, United States

Komansky Children's Hospital of New York Presbyterian

New York, New York, United States

Golisano Children's Hospital

Rochester, New York, United States

Duke University School of Medicine

Durham, North Carolina, United States

Children's Hospital of Richmond at VCU

Richmond, Virginia, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Schneider Children's Medical Center

Petah Tikva, , Israel

Countries

United States; Israel

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R34HL159119-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000034604

Identifier Type: -

Identifier Source: org_study_id