Clinical trial NCT05796557: ECMO Hemostatic Transfusions in Children
Official title: ECMO Hemostatic Transfusions in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Extracorporeal Membrane Oxygenation Complication
Hemorrhage
Thromboembolism
Transfusion Adverse Reaction
Keywords: Platelet transfusion
ECMO
Bleeding
Clotting
Mortality
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Weill Medical College of Cornell University
name: University of Utah
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Columbia University
name: Virginia Commonwealth University
name: University of Rochester
name: Children's Hospital and Health System Foundation, Wisconsin
name: Duke University
name: Johns Hopkins All Children's Hospital
name: University of Iowa
name: Emory University
name: Schneider Medical Children's Center, Israel
First posted: 2023-04-03
Enrollment: 50
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:1 ratio to either arm. Subjects will be stratified by type of extracorporeal membrane oxygenation (ECMO) support (Veno-Arterial vs Veno-Venous), by site, and by age (≤28 days vs \>28 days).
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Total Platelet Transfusion Dose
timeFrame: up to day 21
measure: Pre-transfusion Platelet Count
timeFrame: During intervention
Secondary outcomes:
measure: Feasibility Assessed by the Screening Rate
timeFrame: At screening
measure: Feasibility Assessed by the Inclusion Rate
timeFrame: At screening
measure: Feasibility Assessed by the Number of Informed Consents Signed in the First 24 Hours Post Cannulation.
timeFrame: At screening
measure: Compliance With Transfusion Thresholds
timeFrame: up to Day 21
measure: Participants With at Least One Temporary Suspension
timeFrame: up to Day 21
measure: Duration for Temporary Suspensions
timeFrame: up to Day 21
measure: Progression to Composite Outcome of Severe Bleeding and/or Severe Thrombotic Event
timeFrame: up to Day 21
measure: Number of Participants Who Were Withdrawn and/or Lost to Follow-up
timeFrame: Up to 90 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Emory
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York Presbyterian
state: New York
city: New York
country: United States
facility: Komansky Children's Hospital of New York Presbyterian
state: New York
city: Rochester
country: United States
facility: Golisano Children's Hospital
state: New York
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU
state: Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center
Study officials:
affiliation: Yale University
name: Oliver Karam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: NewYork-Presbyterian / Weill Cornell
name: Marianne Nellis, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: