Evaluation of Safety and Effectiveness of The SherpaPak in Donation After Circulatory Death Heart Transplantation

Study Overview
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Brief Summary
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This is a prospective, pilot trial to evaluate the safety and effectiveness of The Paragonix SherpaPak™ Cardiac Transport System (SherpaPak CTS) in transportation of cardiac allografts recovered from donors after circulatory death with thoracoabdominal normothermic regional perfusion (TA-NRP). SherpaPak™ CTS is an ultraportable hypothermic preservation and transport system that has been approved by United States Food & Drug Administration (FDA) for clinical use in heart transplantation.

Detailed Description
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The investigators will accept donors between the ages of 18 and 49 without any known history of coronary artery disease, insulin dependent diabetes, or long-term smoking (>20 pack/years) and normal baseline cardiac function (EF>50) assessed with transthoracic echocardiogram. Donors will be selected and matched to the recipients based on standard criteria (blood group, cross-match, size match, and clinical stability). The current procedure of donation after circulatory death (DCD) and procurement follows a well-established course. After consent is obtained, the organs are allocated through United Network for Organ Sharing (UNOS). All organs will be recovered with protocolized UNMC DCD TA-NRP technique that involves reestablishment of blood flow in-situ after donor's circulatory arrest using portable venoarterial extracorporeal membrane oxygenation (VA-ECMO). Organs will be transported from a donor site to recipient center with the SherpaPak™ CTS. All organs will be transplanted at Nebraska Medicine. Recipients (subjects) will be followed from transplant through one-year post-transplantation.

Official Title
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Evaluation of Safety and Effectiveness of The Paragonix™ SherpaPak Cardiac Transport System in Donation After Circulatory Death Heart Transplantation

Conditions
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Heart Transplant Failure, Determination of Death, Outcomes Research, Extracorporeal Membrane Oxygenation

Intervention / Treatment
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* Device: Paragonix SherpaPak Cardiac Transport System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient is ≥ 19 years old Recipient, or their designated healthcare proxy, is able and willing to sign informed consent Recipient meets standard listing criteria for heart transplantation Exclusion Criteria: Recipient is < 19 years old Recipient, or their designated healthcare proxy, is unable to sign informed consent Recipient has any condition that, in the opinion of the Investigator, would make study participation unsafe or would interfere with the objectives of the study

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Intervention Model: Single Group Assignment
Interventional Model Description: Cardiac allografts recovered from donors after circulatory death with thoracoabdominal normothermic regional perfusion will be transported with Paragonix SherpaPak Cardiac Transport System to the recipient center
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SherpaPak<br>cardiac allografts recovered from donors after circulatory determined death using thoracoabdominal normothermic regional perfusion will be transported to the recipient center in Paragonix SherpaPak Cardiac Transport System | Device: Paragonix SherpaPak Cardiac Transport System<br>* Transportation of cardiac allografts in a device maintaining constant optimal temperature to minimize freezing tissue injury<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Graft Dysfunction (PGD) | PGD will be classified according to International Society for Heart and Lung Transplantation (ISHLT) classification into: PGD-LV Grade 1 (LVEF ≤ 40% by echocardiography, or Hemodynamics with RAP > 15 mm Hg, PCWP > 20 mm Hg, CI < 2.0 L/min/m2 (lasting more than 1 hour) requiring low-dose inotropes); PGD-LV Grade 2 (I. One criteria from the following: Left ventricular ejection fraction ≤ 40%, or Hemodynamic compromise with RAP > 15 mm Hg, PCWP > 20 mm Hg, CI < 2.0 L/min/m2, hypotension with MAP < 70 mm Hg (lasting more than 1 hour) II. One criteria from the following: High-dose inotropes-Inotrope score >10, or Newly placed IABP (regardless of inotropes)); PGD-LV Grade 3 ( Dependence on left or biventricular mechanical support including ECMO, LVAD, BiVAD, or percutaneous LVAD. Excludes requirement for IABP; PGD-RV (I. Hemodynamics with RAP > 15 mm Hg, PCWP < 15 mm Hg, CI < 2.0 L/min/m2, II. TPG < 15 mm Hg and/or pulmonary artery systolic pressure < 50 mm Hg, III. Need for RVAD) | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for cardioversion or pacing to restart transplanted heart | Need for cardioversion or pacing to restart transplanted heart | 72 hours | 
| Vasoactive-inotropic score (VIS) | The vasoactive-inotropic score (VIS) will be calculated as a weighted sum of all administered inotropes and vasoconstrictors, reflecting pharmacological support of the cardio-vascular system. Formula for VIS calculation: dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 x epinephrine dose (µg/kg/min) + 100 x norepinephrine dose (µg/kg/min). | 24, 48, and 72 hours | 
| Duration of vasoactive-inotropic support in days | Duration of vasoactive-inotropic support in days | 1 year | 
| Intensive Care Unit & Hospital length of stay in days | Intensive Care Unit & Hospital length of stay in days | 1 year | 
| Survival at discharge | Survival at discharge 30-day, 90-day, 1-year | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transplantation, heart, Normothermic Regional Perfusion, Organ transport