Randomized Study of Organ Care System Cardiac for Preservation of Donated Hearts for Eventual Transplantation (PROCEEDII)

Prospective, Multicenter, Randomized, Clinical Investigation of TransMedics Organ Care System (OCS) for Cardiac Use

The purpose of the study is to compare survival of both patients and newly transplanted hearts following heart transplantation among patients who were transplanted with donated hearts preserved on ice and those who were transplanted with donated hearts using the Organ Care System (OCS). The Organ care system preserves the hearts in a warm blood perfused beating state. The study also compares the number of rejection episodes, heart related adverse events, ICU time, and ventilation time between the two groups. The study is considered a success if survival in the OCS group was not inferior to the ice group.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Device: Organ Care System; Device: Cold Cardioplegia Solution

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Hospitalier Pitie-Salpetriere
• Italy
  • Udine, Italy, 33100
    • Azienda Ospedaliera S. Maria della Misericordia
• United Kingdom
  • Cambridge, United Kingdom, CB23 3RE
    • Papworth Hospital
  • London, United Kingdom
    • Harefield Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Los Angeles, California, United States, 90211
      • Cedars-Sinai Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New Jersey
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Recipient Day of Transplant

• Registered male or female primary heart transplant candidate
• ≥18 years old
• Signed, written informed consent document and authorization to use and disclose protected health information

Donor Hearts

• <60 years old
• Mean systolic blood pressure >60 mmHg at the time of final heart assessment
• Satisfactory echocardiography assessment defined as:
• Ejection fraction >40%
• Absence of severe segmental wall motion abnormalities
• Absence of left ventricular hypertrophy (inter ventricular septum and posterior wall thickness <1.3 cm)
• Absence of valve abnormalities (trace to mild valvular regurgitation is acceptable)

Exclusion Criteria:

Recipient Day of Transplant

• >4 previous sternotomies
• Chronic renal failure as defined by chronic serum creatinine >3.0 mg/dL for more than 2 weeks and/or requiring hemodialysis (except for hemodialysis or hemofiltration for fluid overload)
• Ventilator dependence at the time of transplant
• Use of a ventricular assist device for > 30 days and the presence of any of the following: sepsis, intracranial hemorrhage or heparin induced thrombocytopenia
• Panel reactive antibodies > 40% with a positive prospective cross match and/or virtual cross match
• Use of an investigational drug or device, other than OCS, during the study.
• Simultaneous transplant of non-heart allograft, except for concurrent kidney transplant

Donor Hearts

• Abnormal coronary angiogram defined as >50% stenosis, requiring coronary bypass
• Donor-to-recipient body weight ratio of <0.6

• Inotrope support at time of final heart assessment including, but not limited to:

  • Dopamine >10 ug/kg/min
  • Dobutamine > 10 ug/kg/min
  • Milrinone >0.3 ug/kg/min
  • Epinephrine > 0.03 ug/kg/min
  • Norepinephrine > 0.03 ug/kg/min
  • Any bolus dose of the above prior to explants that would result in exceeding the above stated criteria
• Presence of any exclusion criterion based on the standard practice of the investigational site

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Organ Care System	Device: Organ Care System; The Organ Care System (OCS) is a portable organ perfusion and monitoring system intended to preserve a donated heart in a near normal physiologic beating state during transport for eventual transplantation into a recipient. The OCS maintains organ viability by providing a controlled environment that simulates near-normal physiological conditions, continuously perfusing the donated heart with warm, oxygenated blood, supplemented with the Solution Set. The blood is collected from the donor and continuously circulated to the organ in a closed circuit along with the Solution. The OCS preserves and monitors the organ's perfusion and metabolic state after explantation from a donor and connection to the device, during transportation to the recipient site, and until disconnection from the device.; Other Names: OCS
Active Comparator: Cold cardioplegia solution	Device: Cold Cardioplegia Solution; This is the standard of care solutions used to arrest and preserve the donated heart during transport until arrival at recipient hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
30-day patient survival following transplantation with the originally transplanted heart and no mechanical circulatory assist device at day 30	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of all cardiac graft-related serious adverse events	30 days
Incidence of biopsy proven ISHLT grade 2R or 3R acute rejection on any of the surveillance endomyocardial biopsies or clinically symptomatic rejection requiring augmentation of immunosuppressive therapy during the 30 day follow up	30 day
Length of ICU stay	30 day

Collaborators and Investigators

• Sponsor: TransMedics
• Collaborators: Massachusetts General Hospital; University of California, Los Angeles; Columbia University; The Cleveland Clinic; Cedars-Sinai Medical Center; Indiana University; Groupe Hospitalier Pitie-Salpetriere; Royal Brompton & Harefield NHS Foundation Trust; Papworth Hospital NHS Foundation Trust; Azienda Ospedaliera S. Maria della Misericordia; Newark Beth Israel Medical Center
• Investigators: Study Chair: Abbas Ardehali, MD, University of California, Los Angeles

Publications and helpful links

General Publications

• Ardehali A, Esmailian F, Deng M, Soltesz E, Hsich E, Naka Y, Mancini D, Camacho M, Zucker M, Leprince P, Padera R, Kobashigawa J; PROCEED II trial investigators. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet. 2015 Jun 27;385(9987):2577-84. doi: 10.1016/S0140-6736(15)60261-6. Epub 2015 Apr 14.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: March 3, 2009
• First Submitted That Met QC Criteria: March 3, 2009
• First Posted (Estimate): March 4, 2009

Study Record Updates

• Last Update Posted (Actual): June 9, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Heart Failure; Transplant; Warm Perfusion; Organ Care; Resting Mode
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Pharmaceutical Solutions; Cardioplegic Solutions
• Other Study ID Numbers: CAR-05-2008