ECMO Hemostatic Transfusions in Children

Hemorrhage Clinical Trial

— ECSTATIC  

Official title:

ECMO Hemostatic Transfusions in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05796557
• Other study ID #: 2000034604
• Secondary ID: 1R34HL159119-01A
• Status: Recruiting
• Phase: Phase 4
• Start date: December 12, 2023
• Est. completion date: September 1, 2025

Study information

• Verified date: June 2024
• Source: Yale University
• Contact: Oliver Karam, MD, PhD
• Phone: 203-785-4651
• Email: oliver.karam[@]yale.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Extracorporeal Membrane Oxygenation Complication
• Hemorrhage
• Thromboembolism

Intervention

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.

Locations

Country	Name	City	State
Israel	Schneider Children's Medical Center	Petach Tikva
United States	Children's Healthcare of Atlanta - Emory	Atlanta	Georgia
United States	Duke University School of Medicine	Durham	North Carolina
United States	University of Iowa Health Care	Iowa City	Iowa
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Komansky Children's Hospital of New York Presbyterian	New York	New York
United States	Morgan Stanley Children's Hospital of New York Presbyterian	New York	New York
United States	Children's Hospital of Richmond at VCU	Richmond	Virginia
United States	Golisano Children's Hospital	Rochester	New York

Sponsors (13)

Lead Sponsor	Collaborator
Yale University	Children's Hospital and Health System Foundation, Wisconsin, Columbia University, Duke University, Emory University, Johns Hopkins All Children's Hospital, National Heart, Lung, and Blood Institute (NHLBI), Schneider Medical Children's Center, Israel, University of Iowa, University of Rochester, University of Utah, Virginia Commonwealth University, Weill Medical College of Cornell University

Countries where clinical trial is conducted

United States,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pre-transfusion platelet count	Platelet count will be collected before each platelet transfusion.	up to Day 21
Primary	Total platelet transfusion dose	The total dose (in ml/kg/run) will be computed by the research team, by dividing the total platelet transfusion volume by the patient's weight at admission.	up to day 21
Secondary	Feasibility assessed by the screening rate	Feasibility will be assessed by the number of eligible participants that were screened.	Day 1
Secondary	Feasibility assessed by the inclusion rate	Feasibility will be assessed by the number of eligible participants that were enrolled.	Day 1
Secondary	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.	Day 1
Secondary	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
Secondary	Number of temporary suspensions	The number of temporary suspensions during ECMO will be reported.	up to Day 21
Secondary	Duration for temporary suspensions	The investigators will collect information on the duration of each suspension.	up to Day 21
Secondary	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