Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System (TROLLEY)

Multicenter Trial to Evaluate the Safety and Effectiveness of the Cardiohelp System for up to 30 Days of Support in Children With Severe Cardiac Failure

There are two primary goals of this multicenter clinical trial that combines an FDA device trial and a phase II drug trial in the same study cohort. These two goals are to:

1. To evaluate the safety and effectiveness of the Cardiohelp Device for VA-ECMO (heart-lung support) for up to 30 days of support in children with severe heart failure with the goal to support its FDA clearance in children.
2. To evaluate heparin versus bivalirudin as the primary blood thinner (anticoagulant) in a randomized trial of children supported with the Cardiohelp ECMO System with the goal to plan a phase III (pivotal) randomized clinical trial

The main questions the Cardiohelp single-arm trial seeks to answer are:

• What is the safety and effectiveness of the Cardiohelp device for pediatric ECMO?
• Should the Cardiohelp device be FDA-cleared for children based on the results of the study?
• What are the optimal performance specifications of the Cardiohelp device in children?

The main questions the blood thinner randomized trial seeks to answer are:

• Which blood thinner is more promising (i.e., more effective and safer) in children on the Cardiohelp device?
• How should a pivotal trial of heparin vs. bivalirudin be designed so it is the most informative and efficient to determine the best blood thinner?

Children who are receiving the Cardiohelp device will be approached and consented to participate if interested. For the Cardiohelp device trial, participants will undergo a standardized data collection to estimate survival to 30 days and the prevalence of serious adverse events like stroke, bleeding, and hemolysis. For the blood thinner randomized trial, participants will be randomized 1:1 to blood thinner strategy to determine which blood thinner has the fewest bleeding and clotting complications.

For the Cardiohelp single-arm trial, participant outcomes will be compared to performance goals (PG) derived from the ECMO literature. For the blood thinner randomized trial, the amount of bleeding and clotting will be measured.

The study is funded by an R01 grant from the FDA's Office of Orphan Product Development (OOPD).

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Cardiomyopathies; Congenital Heart Disease; Cardiogenic Shock
• Intervention / Treatment: Device: Cardiohelp device (VA-ECMO); Drug: Heparin; Drug: Bivalirudin

Detailed Description

This is a multicenter clinical trial to evaluate the safety and effectiveness of the Cardiohelp System for up to 30 days of support in children with severe cardiac failure. The trial includes a secondary randomized study comparing heparin versus bivalirudin anticoagulation according to standard treatment protocols.

Despite more than 50 years of ECMO use that carries up to 50% mortality, no standalone ECMO device has ever received FDA clearance for pediatric ECMO. All ECMO use in children is off-label, which may contribute to substantial mortality and complications, as well as wide center-to-center variation in ECMO practices that lacks an evidence base. Additionally, while two anticoagulants (heparin and bivalirudin) are commonly used in ECMO circuits, the optimal choice remains unknown-specifically, which anticoagulant is associated with the fewest circuit clots and least bleeding.

This study, funded by an R01 clinical trials Orphan Grant from the FDA, seeks to change the current status quo. By collecting systematic safety and effectiveness data on the Cardiohelp Device, we aim to determine whether it is safe and effective enough to become the first standalone ECMO device to receive FDA clearance for up to 30 days of support in children. The FDA clearance decision will be based on how the Cardiohelp performs relative to several key performance benchmarks drawn from the published ECMO literature, which the FDA has jointly agreed upon. These benchmarks include overall survival without severe stroke, degree of hemolysis (red blood cell breakdown), frequency of circuit change due to thrombus or device malfunction, stroke rate, and kidney injury rate.

For the anticoagulant randomized trial, we will collect systematic data on clotting and bleeding complications associated with each anticoagulant. As a Phase II study, the goal is not to reach a final answer, but to design a Phase III (pivotal) trial that is as informative and efficient as possible for addressing this critical question in the field of ECMO.

Tertiary goals of the study are: (1) to determine the optimal performance range (i.e., device specifications) for the Cardiohelp device in children to inform an eventual FDA label and Instructions for Use (IFU); and (2) to provide the FDA with a predicate device to support FDA clearance of other ECMO systems under 510(k) regulation, as no predicate devices currently exist to support such regulatory comparisons.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Selena Gonzales, MPH; Phone Number: 650-723-7913; Email: selena.gonzales@stanford.edu
• Study Contact Backup: Name: Christopher SD Almond, MD, MPH; Phone Number: 6507237913; Email: calmond@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Lucile Packard Children's Hospital
      • Contact: Kate Ryan, MD; Phone Number: 650-724-5554; Email: kateryan@stanford.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Cuimc/Nyph
      • Contact: Eva Cheung, MD; Phone Number: (212) 305-8458; Email: ec2335@cumc.columbia.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Caroline Ozment, MD; Email: caroline.ozment@duke.edu
  • Texas
    • Dallas, Texas, United States, 95235
      • Recruiting
      • Children's Health Dallas
      • Contact: Sirine Baltagi, MD; Email: Sirine.Baltagi@UTSouthwestern.edu
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Michael McMullan, MD; Phone Number: 206-987-2015; Email: michael.mcmullan@seattlechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Study Population

All children between 0 and 16 years of age supported with the VA-ECMO using the Cardiohelp system for primary myocardial failure where all other treatment options have failed, and clinical deterioration is expected, or risk of death is imminent.

Description

Inclusion Criteria:

1. Age 0 to 16 years of age (i.e., <17 years)
2. Body weight 3 to 80 kilograms
3. VA-ECMO use for primary cardiac failure using the Cardiohelp system.
4. First ECMO run during the current hospitalization

Exclusion Criteria:Children must not meet any of the following exclusion criteria within 48 hours prior to device implant:

1. Gestationally-corrected age <37 weeks
2. Bleeding or coagulopathy that is a contraindication to anticoagulation
3. Irreversible renal, hepatic or lung failure
4. Stroke or uncertain neurological status within the past 30 days
5. Severely malnourished
6. Use of an ECMO system other than the Cardiohelp
7. VV-ECMO or ECMO for primary respiratory failure
8. Goals of patient to focus on comfort measures only.
9. Failure to separate from cardiopulmonary bypass
10. Allergy or contraindication to receiving UFH or bivalirudin as a primary anticoagulant on ECMO.
11. Patients who are pregnant or breastfeeding.
12. Unable to undergo randomization within 30 hours following ECMO cannulation (randomized cohort only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardiohelp device managed according to a standardized guideline using heparin anticoagulation; Participants receiving the Cardiohelp device for severe heart failure will be managed according to a standardized treatment guideline (equipment, monitoring, etc.) where heparin is the primary blood thinner to estimate the safety and effectiveness of the device and blood thinner strategy for up to 30 days of support.	Device: Cardiohelp device (VA-ECMO); The Cardiohelp system is a compact cardiopulmonary support system used off-label for ECMO for patients with cardiac and/or respiratory failure. It is currently FDA-cleared for <6 hours of support for cardiopulmonary bypass.; Drug: Heparin; Blood thinner that works by inactivating factor Xa that is administered as a continuous intravenous infusion.
Experimental: Cardiohelp device managed according to a standardized guideline using bivalirudin anticoagulation; Participants receiving the Cardiohelp device for severe heart failure will be managed according to a standardized treatment guideline (equipment, monitoring, etc.) where bivalirudin is the primary blood thinner to estimate the safety and effectiveness of the device and blood thinner strategy for up to 30 days of support.	Device: Cardiohelp device (VA-ECMO); The Cardiohelp system is a compact cardiopulmonary support system used off-label for ECMO for patients with cardiac and/or respiratory failure. It is currently FDA-cleared for <6 hours of support for cardiopulmonary bypass.; Drug: Bivalirudin; Blood thinner that works by inhibiting thrombin directly that is administered as a continuous intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival to 30 days, recovery, ventricular assist device implant or transplant in the absence of severe symptomatic stroke (primary device effectiveness)	Survival in the absence of severe symptomatic stroke to 30 days or decannulation for recovery, transplant or VAD implant. For patients with stroke definitely or probably related to ECMO, symptoms and severity will be determined at hospital discharge or 90 days, whichever is first.	30 days of ECMO support or ECMO explant, whichever is earlier.
Symptomatic stroke (primary device safety)	For patients with stroke definitely or probably related to ECMO, the presence of stroke symptoms and its severity will be determined at hospital discharge or 90 days, whichever is first.	30 days of ECMO support or ECMO explant, whichever is earlier.
Severe hemolysis (primary device safety)	Severe hemolysis as defined by the plasma-free hemoglobin level >100 mg/dL confirmed on repeat testing and outside the first 72 hours that is probably or definitely related to the device.	30 days of ECMO support or ECMO explant, whichever is earlier.
Circuit change due to thrombus (primary device safety)	ECMO circuit change due primarily to thrombus that is probably or definitely related to the device.	30 days of ECMO support or ECMO explant, whichever is earlier.
Circuit change due primarily to device malfunction (primary device safety)	Circuit change due primarily to device malfunction that is probably or definitely related to the device.	30 days of ECMO support or ECMO explant, whichever is earlier.
Renal injury/failure (primary device safety)	renal injury/failure defined as three times the upper limit of normal or 3X baseline if the baseline is above the upper limit of normal.	30 days of ECMO support or ECMO explant, whichever is earlier.
Circuit-change free survival primarily due to thrombus (primary safety endpoint for anticoagulation RCT)	Circuit-change free survival where the circuit is change is primarily due to thrombus and is definitely or probably related to the anticoagulant (primary safety endpoint for anticoagulation RCT)	30 days of ECMO support or ECMO explant, whichever is earlier.
Bleeding	Total red blood cell transfusion volume in cc/kg/day probably or definitely related to the anticoagulant.	30 days of ECMO support or ECMO explant, whichever is earlier.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of all serious adverse events	Incidence rate of all serious adverse events (per day of support)	30 days
NHLBI bleeding and clotting score	The bleeding and clotting score as categorized by the ordinal 5-grade NHLBI score.	through 30 days of ECMO support or ECMO explant, whichever is earlier.

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Boston Children's Hospital; Duke University; FDA Office of Orphan Products Development
• Investigators: Principal Investigator: Lynn Sleeper, ScD, Boston Children's Hospital; Principal Investigator: Caroline Ozment, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: heart failure; ECMO; blood thinner; heparin; bivalirudin; FDA regulation; pediatric medical devices; 510k clearance
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Congenital Abnormalities; Cardiovascular Abnormalities; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Heart Failure; Heart Defects, Congenital; Cardiomyopathies; Shock, Cardiogenic; Carbohydrates; Glycosaminoglycans; Polysaccharides; Heparin; bivalirudin
• Other Study ID Numbers: 72467; 1R01FD007833-01A1 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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