ECMOPhase 1/2PACENCT07837869

PACE: Prostacyclin AntiCoagulation in ECMO

A Phase 1/2 study testing Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO in people with ECMO, run by Garrett Keim at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 0 days to 17 years
Conditions the study is for: ECMO
What is being tested?: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 44 participants
Where: 1 siteUnited States
Study dates: Oct 2026to Aug 2028
Phase: Phase 1/2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 0 days to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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).

Who cannot join

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.

Show all 12Show fewer

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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Adam Himebauch, MD, MSCE contact

610-731-5833

HIMEBAUCHA@chop.edu

Garrett Keim, MD, MSCE contact

814-490-2276

KeimG@chop.edu

United States1 site

Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Adam Himebauch, MD, MSCE, 610-731-5833, HIMEBAUCHA@chop.edu

Other trials in United States

About this study

Official title: Phase 1/2 Dose-Escalation Study of Epoprostenol as Adjunct Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation (ECMO)

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:

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?
How does epoprostenol move through the ECMO circuit?
What is the effect of epoprostenol on platelet function at different doses?

Participants receiving V-V or V-A ECMO with at least 12 hours of stable blood pressures and 6 hours of blood thinning within clinical practice goal, who agree to participate, will receive a 48-hour infusion of epoprostenol with associated blood sampling and adverse event monitoring. The three doses of epoprostenol in this dose-escalation study are 4 ng/kg/min, 8 ng/kg/min, and 12 ng/kg/min. Starting with the lowest dose, each participant will receive one dose throughout the 48 hours with close monitoring for side effects. The 3 major side effects that are being tracked are: 1) effects on blood pressure, 2) effects on unexpected bleeding, and 3) effects on fluid in the lungs.

Conditions: ECMO
Being tested: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO
Keywords: ECMO, Epoprostenol

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMODrug
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.

Study groups in NCT07837869
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Within 72 hours of epoprostenol initiation

Secondary outcomes (5)

Determination of the Steady State Concentration of Epoprostenol Metabolites
We will determine the steady-state concentration (Css) of epoprostenol metabolites in each patient. In a standard patient receiving drug by continuous infusion, Css is defined as: Css = R0/CL, where R0 is the rate of infusion and CL is the patient's clearance of the drug. In a patient on ECMO, clearance will include patient clearance (CLp) and sequestration of drug by the circuit (CLs).
The half-life of epoprostenol metabolites is ~15 minutes, so our first PK sampling time point (4 hours) will allow evaluation of ongoing sequestration across the ECMO circuit, since the patient should be at steady state at this time. We will compare metabolite concentrations at the 3 sampling sites - pre-membrane, post-membrane, and patient (arterial) - to determine sequestration at this time point. It is expected that sequestration is saturable and will not be ongoing at 24 hours.
Measured: Within 48 hrs of epoprostenol initiation
Population Pharmacokinetic Analysis
As an exploratory analysis, we will perform population PK (popPK) analysis using all available concentration data from enrolled patients. The objective of the popPK analysis is to develop metabolite-only models for each metabolite. Since parent drug concentrations will not be available, we will assume a two-compartment structure where drug is administered into the first (latent) compartment and only the 2nd compartment is observed. In this setup, k12 will represent formation of the metabolite. Because the fraction of parent drug converted to each metabolite will not be known, all PK parameters (CL, V) will be apparent parameters. As the data allows, more complex model structures will be explored. Covariate analysis will be used to statistically evaluate how factors relating to ECMO (flow rate, circuit age, etc.) and the patient (age, renal function, etc.) influence epoprostenol metabolite PK.
Measured: Within 48 hours of epoprostenol infusion
Thromboelastography (TEG) with platelet mapping
To evaluate the effect of epoprostenol on platelet function within the ECMO circuit environment and patient, thromboelastography (TEG) with platelet mapping, focusing on the Maximum Amplitude (MA) parameter, will be measured at various timepoints during epoprostenol infusion.
Measured: Within 48 hours of epoprostenol intiation
Light-transmission aggregometry
To evaluate the effect of epoprostenol on platelet function within the ECMO circuit environment and patient, light-transmission aggregometry against ADP, thrombin, TRAP, and CRP-A agonists will be utilized at various timepoints during epoprostenol infusion.
Measured: Within 48 hours of epoprostenol intiation
Platelet activation measurement through whole-blood flow cytometry
To evaluate the effect of epoprostenol on platelet function within the ECMO circuit environment and patient, whole-blood flow cytometry for PAC-1, P-selectin, and CD41 at baseline and post-agonist stimulation will be measured at various timepoints during epoprostenol infusion:
Measured: Within 48 hours of epoprostenol intiation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2026Aug 2028

First posted24 Sep 2026
Study startOct 2026 (estimated)
Primary completionFeb 2028 (estimated)
Study completionAug 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (25)Papers the sponsor has linked to this study.
Other trials for ECMOStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 44 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07837869
Sponsor's protocol ID: 26-024418
Acronym: PACE
Status last verified: Sep 2026
First submitted: 11 Sep 2026
Last updated: 24 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: De-identified individual participant data underlying published results, with a data dictionary, will be shared with qualified investigators. Sharing is limited to participants who consent at enrollment to future research use. Because enrollment is small and single-center in a rare pediatric population, the scope of the shareable dataset will be set by a formal expert determination of re-identification risk under 45 CFR 164.514(b)(1), conducted once final enrollment and consent numbers are known. If participant-level release is not feasible, sharing will be limited to aggregate or derived data as that determination permits, and this record will be updated. Sharing occurs after FDA reporting obligations under IND 182435 are fulfilled and requires an executed data use agreement.

Publications

Matics TJ, Sanchez-Pinto LN. Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children. JAMA Pediatr. 2017 Oct 2;171(10):e172352. doi: 10.1001/jamapediatrics.2017.2352. Epub 2017 Oct 2.
PubMed 28783810
Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F; Groupe Francophone de Reanimation et d'Urgences Pediatriques (GFRUP). PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit Care Med. 2013 Jul;41(7):1761-73. doi: 10.1097/CCM.0b013e31828a2bbd.
PubMed 23685639
Pollack MM, Holubkov R, Funai T, Dean JM, Berger JT, Wessel DL, Meert K, Berg RA, Newth CJ, Harrison RE, Carcillo J, Dalton H, Shanley T, Jenkins TL, Tamburro R; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. The Pediatric Risk of Mortality Score: Update 2015. Pediatr Crit Care Med. 2016 Jan;17(1):2-9. doi: 10.1097/PCC.0000000000000558.
PubMed 26492059
Aldairi N, Al Ali AS, Alabdulqader M, Al Jeraisy M, Cyrus J, Karam O. Efficacy of Prostacyclin Anticoagulation in Critically Ill Patients Requiring Extracorporeal Support: A Systematic Review and Meta-Analysis. Cureus. 2023 Jun 5;15(6):e39967. doi: 10.7759/cureus.39967. eCollection 2023 Jun.
PubMed 37416033
Deep A, Alexander EC, Khatri A, Kumari N, Sudheendhra K, Patel P, Joarder A, Elghuwael I. Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019. Pediatr Crit Care Med. 2024 Jan 1;25(1):15-23. doi: 10.1097/PCC.0000000000003371. Epub 2023 Sep 12.
PubMed 38169336
Sondhi E, Stewart M, Harper J, Konyk L, McSteen C, Crowley KL, Kim-Campbell N, Fabio A, Fuhrman DY. A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy. Blood Purif. 2024;53(10):838-846. doi: 10.1159/000540302. Epub 2024 Jul 18.
PubMed 38991509
Nicolas LB, Krause A, Gutierrez MM, Dingemanse J. Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects. Br J Clin Pharmacol. 2012 Dec;74(6):978-89. doi: 10.1111/j.1365-2125.2012.04301.x.
PubMed 22515646
Ylikorkala D, Viinikka L. Measurement of 6-keto-prostaglandin E1 alpha in human plasma with radioimmunoassay: effect of prostacyclin infusion. Prostaglandins Med. 1981 Apr;6(4):427-36. doi: 10.1016/0161-4630(81)90075-6.
PubMed 7025068
Mattke AC, Johnson K, Gibbons K, Long D, Robertson J, Venugopal PS, Blumenthal A, Schibler A, Schlapbach L. Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2023 Mar 15;12:e43760. doi: 10.2196/43760.
PubMed 36920455
Chaumais MC, Jobard M, Huertas A, Vignand-Courtin C, Humbert M, Sitbon O, Rieutord A, Montani D. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1587-98. doi: 10.1517/17425255.2010.534458.
PubMed 21077785
Kimmelstiel C, Zhang P, Kapur NK, Weintraub A, Krishnamurthy B, Castaneda V, Covic L, Kuliopulos A. Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2011 Apr 1;4(2):171-9. doi: 10.1161/CIRCINTERVENTIONS.110.959098. Epub 2011 Mar 1.
PubMed 21364148
Valdes CA, Sharaf OM, Bleiweis MS, Jacobs JP, Mumtaz M, Sharaf RM, Jeng EI, Peek GJ. Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review. Front Med (Lausanne). 2023 Mar 14;10:1137134. doi: 10.3389/fmed.2023.1137134. eCollection 2023.
PubMed 36999064
Seelhammer T, Ninan J, Nei S, Nabzdyk CG, Wang Z, Gerberi D, Wieruszewski PM. Anticoagulation during extracorporeal membrane oxygenation. Cochrane Database Syst Rev. 2024 Jun 10;6(6):CD015685. doi: 10.1002/14651858.CD015685.
PubMed 39804113
Liu L, Liu F, Tan J, Zhao L. Bivalirudin versus heparin in adult and pediatric patients with extracorporeal membrane oxygenation therapy: A systematic review and meta-analysis. Pharmacol Res. 2022 Mar;177:106089. doi: 10.1016/j.phrs.2022.106089. Epub 2022 Jan 20.
PubMed 35065202
Li MJ, Shi JY, Zhang JH. Bivalirudin vs. heparin in paediatric and adult patients on extracorporeal membrane oxygenation: A meta-analysis. Br J Clin Pharmacol. 2022 Jun;88(6):2605-2616. doi: 10.1111/bcp.15251. Epub 2022 Feb 14.
PubMed 35098565

Interested in taking part?

Adam Himebauch, MD, MSCE

610-731-5833

HIMEBAUCHA@chop.edu

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Pharmacokinetics of Sedatives and Analgesics During Extracorporeal Membrane Oxygenation (ECMO) Support
Drug Effect
Recruiting
Platform of Randomized Adaptive Clinical Trials in Critical Illness
Respiratory Insufficiency, Extracorporeal Membrane Oxygenation Complication
RecruitingObservational study
Factors Influencing Outcomes in ECMO and Impella Patients: Metabolic and Thyroid Hormone Dynamics
Cardiogenic Shock, Euthyroid Sick Syndrome
RecruitingObservational study
CytOSorb TreatMent Of Critically Ill PatientS Registry
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All ECMO trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1/2 Dose-Escalation Study of Epoprostenol as Adjunct Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation (ECMO)
ClinicalTrials.gov ID: NCT07837869
Acronym / sponsor ID: PACE / 26-024418
Conditions: ECMO
Keywords: ECMO, Epoprostenol
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 44 participants (estimated)
Lead sponsor: Garrett KeimUniversity, hospital or other
Study start: Oct 2026 (estimated)
Primary completion: Feb 2028 (estimated)
Study completion: Aug 2028 (estimated)
First posted: 24 Sep 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The main questions this study aims to answer are:

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?
How does epoprostenol move through the ECMO circuit?
What is the effect of epoprostenol on platelet function at different doses?

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Statum A: 4 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.
Statum B: 4 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.
Statum A: 8 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.
Statum B: 8 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.
Statum A: 12 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.
Statum B: 12 ng/kg/min	Experimental	Drug: Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOPatients 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.

Who may qualify

Ages: 0 days to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

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).

Key exclusion criteria (12 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMOEpoprostenol 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.	Drug	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

Primary outcome

Safety and Maximum Tolerated Dose
Time frame: Within 72 hours of epoprostenol initiation
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

5 secondary outcomes

Determination of the Steady State Concentration of Epoprostenol Metabolites
Time frame: Within 48 hrs of epoprostenol initiation
Population Pharmacokinetic Analysis
Time frame: Within 48 hours of epoprostenol infusion
Thromboelastography (TEG) with platelet mapping
Time frame: Within 48 hours of epoprostenol intiation
Light-transmission aggregometry
Time frame: Within 48 hours of epoprostenol intiation
Platelet activation measurement through whole-blood flow cytometry
Time frame: Within 48 hours of epoprostenol intiation

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
Background: PubMed 28783810Matics TJ, Sanchez-Pinto LN. Adaptation and Validation of a Pediatric Sequential Organ Failure Assessment Score and Evaluation of the Sepsis-3 Definitions in Critically Ill Children. JAMA Pediatr. 2017 Oct 2;171(10):e172352. doi: 10.1001/jamapediatrics.2017.2352. Epub 2017 Oct 2.
Background: PubMed 23685639Leteurtre S, Duhamel A, Salleron J, Grandbastien B, Lacroix J, Leclerc F; Groupe Francophone de Reanimation et d'Urgences Pediatriques (GFRUP). PELOD-2: an update of the PEdiatric logistic organ dysfunction score. Crit Care Med. 2013 Jul;41(7):1761-73. doi: 10.1097/CCM.0b013e31828a2bbd.
Background: PubMed 26492059Pollack MM, Holubkov R, Funai T, Dean JM, Berger JT, Wessel DL, Meert K, Berg RA, Newth CJ, Harrison RE, Carcillo J, Dalton H, Shanley T, Jenkins TL, Tamburro R; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. The Pediatric Risk of Mortality Score: Update 2015. Pediatr Crit Care Med. 2016 Jan;17(1):2-9. doi: 10.1097/PCC.0000000000000558.
Background: PubMed 37416033Aldairi N, Al Ali AS, Alabdulqader M, Al Jeraisy M, Cyrus J, Karam O. Efficacy of Prostacyclin Anticoagulation in Critically Ill Patients Requiring Extracorporeal Support: A Systematic Review and Meta-Analysis. Cureus. 2023 Jun 5;15(6):e39967. doi: 10.7759/cureus.39967. eCollection 2023 Jun.
Background: PubMed 38169336Deep A, Alexander EC, Khatri A, Kumari N, Sudheendhra K, Patel P, Joarder A, Elghuwael I. Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019. Pediatr Crit Care Med. 2024 Jan 1;25(1):15-23. doi: 10.1097/PCC.0000000000003371. Epub 2023 Sep 12.
Background: PubMed 38991509Sondhi E, Stewart M, Harper J, Konyk L, McSteen C, Crowley KL, Kim-Campbell N, Fabio A, Fuhrman DY. A Comparison of the Anticoagulation Efficacy and Safety of Epoprostenol to Heparin and Citrate in Children Receiving Continuous Renal Replacement Therapy. Blood Purif. 2024;53(10):838-846. doi: 10.1159/000540302. Epub 2024 Jul 18.
Background: PubMed 22515646Nicolas LB, Krause A, Gutierrez MM, Dingemanse J. Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects. Br J Clin Pharmacol. 2012 Dec;74(6):978-89. doi: 10.1111/j.1365-2125.2012.04301.x.
Background: PubMed 7025068Ylikorkala D, Viinikka L. Measurement of 6-keto-prostaglandin E1 alpha in human plasma with radioimmunoassay: effect of prostacyclin infusion. Prostaglandins Med. 1981 Apr;6(4):427-36. doi: 10.1016/0161-4630(81)90075-6.
Background: PubMed 36920455Mattke AC, Johnson K, Gibbons K, Long D, Robertson J, Venugopal PS, Blumenthal A, Schibler A, Schlapbach L. Nitric Oxide on Extracorporeal Membrane Oxygenation in Neonates and Children (NECTAR Trial): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2023 Mar 15;12:e43760. doi: 10.2196/43760.
Background: PubMed 21077785Chaumais MC, Jobard M, Huertas A, Vignand-Courtin C, Humbert M, Sitbon O, Rieutord A, Montani D. Pharmacokinetic evaluation of continuous intravenous epoprostenol. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1587-98. doi: 10.1517/17425255.2010.534458.
Background: PubMed 21364148Kimmelstiel C, Zhang P, Kapur NK, Weintraub A, Krishnamurthy B, Castaneda V, Covic L, Kuliopulos A. Bivalirudin is a dual inhibitor of thrombin and collagen-dependent platelet activation in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2011 Apr 1;4(2):171-9. doi: 10.1161/CIRCINTERVENTIONS.110.959098. Epub 2011 Mar 1.
Background: PubMed 36999064Valdes CA, Sharaf OM, Bleiweis MS, Jacobs JP, Mumtaz M, Sharaf RM, Jeng EI, Peek GJ. Heparin-based versus bivalirudin-based anticoagulation in pediatric extracorporeal membrane oxygenation: A systematic review. Front Med (Lausanne). 2023 Mar 14;10:1137134. doi: 10.3389/fmed.2023.1137134. eCollection 2023.
Individual participant dataSharing planned: Yes. De-identified individual participant data underlying published results, with a data dictionary, will be shared with qualified investigators. Sharing is limited to participants who consent at enrollment to future research use. Because enrollment is small and single-center in a rare pediatric population, the scope of the shareable dataset will be set by a formal expert determination of re-identification risk under 45 CFR 164.514(b)(1), conducted once final enrollment and consent numbers are known. If participant-level release is not feasible, sharing will be limited to aggregate or derived data as that determination permits, and this record will be updated. Sharing occurs after FDA reporting obligations under IND 182435 are fulfilled and requires an executed data use agreement.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Adam Himebauch, MD, MSCE contact

610-731-5833

HIMEBAUCHA@chop.edu

Garrett Keim, MD, MSCE contact

814-490-2276

KeimG@chop.edu

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dose-escalation study of epoprostenol as adjunct anticoagulation in ECMO in people with ECMO, run by Garrett Keim at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Adam Himebauch, MD, MSCE (610-731-5833, HIMEBAUCHA@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Maximum Tolerated Dose (time frame: Within 72 hours of epoprostenol initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07837869, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.