PACE: Prostacyclin AntiCoagulation in ECMO

NCT07837869 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 26-024418
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Extracorporeal membrane oxygenation (ECMO) is a machine that temporarily supports the heart and/or lungs and is a critical rescue therapy for refractory cardiac and respiratory failure in pediatric populations. Despite technological advancements, the contact between blood and the artificial surface of the ECMO circuit often triggers blood clotting that requires blood thinning medications while on ECMO. The current standard of care is to use medications that have little effect on platelets, a part of the clotting system that can be activated by parts of the ECMO machine. The goal of this clinical trial is to find the safest dose of a medication called epoprostenol (also known as Veletri) when it is given directly into the ECMO circuit and investigate its pharmacokinetics and effect on platelets for patients on ECMO. This medication is primarily used for the management of patients with pulmonary hypertension and does have a known side effect of decreasing platelet activation. This clinical trial is investigating what doses of this medication are safe in ECMO populations and if there is a measurable effect on platelet function with the trial doses. There is the possibility of direct benefit to the participant because if epoprostenol reduces platelet activation in the ECMO circuit it could potentially decrease ECMO circuit clotting events or reduce the need for escalation of other systemic blood thinning medications during the 48-hour infusion. The main questions this study aims to answer are:

1. 1.What is the safest and maximum tolerated dose (MTD) of continuous intravenous (IV) epoprostenol when administered as an additional anticoagulant in pediatric patients receiving veno-arterial (V-A) or veno-venous (V-V) ECMO?
2. 2.How does epoprostenol move through the ECMO circuit?
3. 3.What is the effect of epoprostenol on platelet function at different doses?

Conditions

ECMO

Keywords

ECMO; Epoprostenol

Outcome Measures

Primary Outcomes (1)

• Safety and Maximum Tolerated Dose

  The primary outcome is to determine the MTD of continuous infusion epoprostenol, defined as a DLT rate ≥ 33.3% after a cohort has enrolled and study drug received. There are 3 DLTs defined for this study and will be followed for 24 hours after end of infusion: 1. Adverse Hemodynamic Effects - in the first 4 hours following target dose, sustained decreases in mean arterial pressure, increases in vasopressor/inotropic support, or administration of 40 mL/kg or \>2 L of fluid to treat hypotension; between 4-72h if any of the above hemodynamic changes occur, the independent medical monitor (IMM) will adjudicate 2. Clinically Significant Bleeding - adapted from ECMO-CENTRAL definitions for the duration of epoprostenol infusion 3. Clinically Significant Pulmonary Edema - in the first 4 hours following target dose and defined through combination of changes in lung ultrasound score and changes in oxygenation; between 4-72h if any of the above hemodynamic changes occur, the IMM will adjudicate

  Within 72 hours of epoprostenol initiation

Secondary Outcomes (5)

• Determination of the Steady State Concentration of Epoprostenol Metabolites

  Within 48 hrs of epoprostenol initiation

• Population Pharmacokinetic Analysis

  Within 48 hours of epoprostenol infusion

• Thromboelastography (TEG) with platelet mapping

  Within 48 hours of epoprostenol intiation

• Light-transmission aggregometry

  Within 48 hours of epoprostenol intiation

• Platelet activation measurement through whole-blood flow cytometry

  Within 48 hours of epoprostenol intiation

Other Outcomes (4)

• Exploratory Efficacy

  Within 72 hrs of epoprostenol initiation

• Platelet transfusion Requirements

  ECMO Duration

• Platelet Count Trend

  ECMO Duration

Study Arms (6)

Statum A: 4 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum A: \< 10kg. Escalation will proceed independently within each stratum. The epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 4 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Statum B: 4 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum B: ≥ 10kg. Escalation will proceed independently within each stratum. The epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 4 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Statum A: 8 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum A: \< 10kg. Escalation will proceed independently within each stratum. For this arm the epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 8 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Statum B: 8 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum B: ≥10kg. Escalation will proceed independently within each stratum. For this arm the epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 8 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Statum A: 12 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum A: \< 10kg. Escalation will proceed independently within each stratum. In this arm, the epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 12 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Statum B: 12 ng/kg/min

EXPERIMENTAL

Patients will be enrolled into two distinct strata based on weight: Stratum B: ≥10kg. Escalation will proceed independently within each stratum. In this arm, the epoprostenol infusion will start at 2 ng/kg/min and increase 2 ng/kg/min every 15 minutes to the goal dose of 12 ng/kg/min for the remainder of the study period or until other stopping criteria are met.

Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

Interventions

Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO DRUG

Epoprostenol infusion administered pre-ECMO lung membrane for a maximum of 48 hours with associated blood sampling and adverse event monitoring. The 3 doses of epoprostenol in this dose-escalation study are 4 ng/kg/min, 8 ng/kg/min, and 12 ng/kg/min.

Statum A: 12 ng/kg/min; Statum A: 4 ng/kg/min; Statum A: 8 ng/kg/min; Statum B: 12 ng/kg/min; Statum B: 4 ng/kg/min; Statum B: 8 ng/kg/min

Eligibility Criteria

• Age: 0 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≤ 17.5 years of age at the time of ECMO initiation.
• Corrected Gestational Age ≥ 37 weeks at the time of ECMO initiation.
• Admitted to the PICU, CICU, or NI/ICU requiring V-A or V-V ECMO support.
• Receiving standard systemic anticoagulation with Unfractionated Heparin (UFH) or Bivalirudin
• Written informed consent provided by the patient's parent or Legally Authorized Representative (LAR).

You may not qualify if:

• Active bleeding: Any active bleeding requiring \>20ml/kg or ≥2 Units of Packed Red Blood Cells in the prior 12 hours.
• Known intracranial hemorrhage during acute hospitalization either prior to or during ECMO.
• Severe coagulopathy: Platelet count \< 50,000/ uL or Fibrinogen \< 50 mg/dL at baseline.
• Known or suspected qualitative platelet dysfunction disorder (congenital bleeding disorder)
• Clinical Contraindication to vasodilation: Severe left ventricular outflow tract obstruction (e.g., HOCM, severe aortic stenosis, or post-capillary cause of pulmonary hypertension).
• Prior major bleeding episode during current hospitalization including gastrointestinal bleed that required \> 20ml/kg or ≥2 Units of PRBCs in a 12-hour period.
• Known hypersensitivity to epoprostenol
• Patients with known esophageal varices
• Systemic prostacyclin therapy for pulmonary hypertension
• Moribund clinical condition as assessed by the investigators and/or clinical team
• Positive pregnancy test
• Inability to achieve hemodynamic and anticoagulation stability as previously defined in the first 7 days of ECMO support.

Sponsors & Collaborators

• Garrett Keim: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

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MeSH Terms

Interventions

Extracorporeal Membrane Oxygenation

Intervention Hierarchy (Ancestors)

Respiratory Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Central Study Contacts

Adam Himebauch, MD, MSCE

CONTACT

610-731-5833; HIMEBAUCHA@chop.edu

Garrett Keim, MD, MSCE

CONTACT

814-490-2276; KeimG@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology And Critical Care Medicine

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 24, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months after publication of the primary results and ending 5 years after publication.
• Access Criteria: Requests should be submitted in writing to the sponsor-investigator at keimg@chop.edu. Requests must include a specific research question, a statistical analysis plan, a description of the intended use and planned output, and documentation of IRB approval or exemption at the requesting institution. Requests are reviewed by the sponsor-investigator and study team for scientific merit, consistency with the scope of participant future-use consent, and consistency with the expert determination of re-identification risk. Approved requests require an executed data use agreement between the requesting institution and the Children's Hospital of Philadelphia that prohibits re-identification and onward transfer.

Locations

US (1)