ECMO Hemostatic Transfusions in Children — ECSTATIC  

Hemorrhage Clinical Trial

Official title: ECMO Hemostatic Transfusions in Children

Status Recruiting

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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Extracorporeal Membrane Oxygenation Complication
• Hemorrhage
• Thromboembolism

• NCT number: NCT05796557
• Study type: Interventional
• Source: Yale University
• Contact: Oliver Karam, MD, PhD
• Phone: 203-785-4651
• Email: oliver.karam@yale.edu
• Status: Recruiting
• Phase: Phase 4
• Start date: December 12, 2023
• Completion date: September 1, 2025