Clinical Trial of New Hypothermic Oxygenated Perfusion System Versus Static Cold Storage

September 25, 2019 updated by: Matteo Ravaioli, MD, University of Bologna

Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol of a Randomised Single Center Clinical Trial of Hypothermic Oxygenated Perfusion Versus Static Cold Storage

With the present study the investigators will evaluate the benefit of end-ischemic HOPE on ECD grafts (livers and kidneys) as compared to SCS. Organs will be perfused through a recently developed machine perfusion (MP) device, from the beginning of back-table procedures till implantation, without increasing CIT. The aim of the study will be demonstrating the ability of HOPE to improve graft function and post-operative outcomes of ECD kidney and liver recipients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Extended criteria donors (ECD) are widely utilized due to organ shortage, but this may increase the risk of graft dysfunction and of poorer outcomes.

Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, which allows to redirect anaerobic metabolism to aerobic metabolism under hypothermic conditions and to protect grafts from oxidative species-related damage; these mechanisms may potentially improve graft function and survival.

Methods This is an open-label, randomized multicenter clinical trial with the aim of comparing HOPE vs. static cold storage (SCS) in ECD kidney and liver transplantation.

In the study protocol - approved by ethics committee - 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to HOPE will be perfused by machine perfusion with cold Belzer solution (4°-10°C) and with continuous oxygenation (partial pressure of oxygen = 500-600 mmHg). In the control group, livers and kidneys undergoing SCS will be steeped in Celsior or University of Wisconsin Belzer solutions and stored in ice. Using the same perfusion machine for both liver and kidney grafts, organs will be perfused from the start of the back-table procedure until implantation, without increasing cold ischemia time (CIT). For each group the investigators will evaluate clinical outcomes, graft function tests and histologic findings, as well as perfusate and the number of allocated organs.

Study Type

Interventional

Enrollment (Anticipated)

220

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Bologna, Italy, 40138
        • Recruiting
        • Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
        • Contact:
        • Principal Investigator:
          • Matteo Ravaioli, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • For kidneys: donor age ≥ 60 years or 50-59 years with two or more of the sequent risk factors: death due to cerebrovascular accident, history of hypertension, donor serum creatinine > 1.5 mg/dL, cold ischemia time (CIT) > 20 h;
  • For livers: donors with hemodynamic deterioration, donor age > 65 years, donor body mass index > 30 kg/m2, serum bilirubin > 3 mg/dl, AST or ALT above three times the upper reference threshold, sodium > 165 mmol/l, intensive care unit (ICU) stay > 7 days, steatosis > 40%, CIT > 12 h.

Exclusion Criteria:

  • Donor age ≤18 years;
  • Donors after circulatory death (DCD) will be excluded, because Italian law requires 20 minutes of "no touch period" before death declaration, causing prolonged warm ischemia and subsequent mandatory perfusion of the organ.
  • Split-liver recipients, liver transplantation (LT) for acute liver failure, pre-emptive renal transplant, dual kidney transplantation, and patients with intra-operative surgical complications before the organ implantation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Kidney-Hypothermic oxygenated
Belzer machine perfusion solution at 4°C-10°C in sterile conditions and continuous oxygenation (partial pressure of oxygen=500-600 mmHg) will be used for perfusion 2000 ml for kidneys.
Device: Kidney-Hypothermic oxygenated

Kidney perfusion will be performed through the renal artery at 25-30 mmHg pressure.

Flow, pressure and temperature will be monitored and registered on a Universal Serial Bus (USB) memory system during organ perfusion. Gas analysis of the effluent perfusate will be accomplished at the start of perfusion (T0) then every 30 minutes. Two perfusate samples will be collected at the beginning and at the end of perfusion to rule out bacterial or fungal contamination.

HOPE will start by flushing the organ at low flow values (20 ml/min) with new oxygenated perfusion fluid during back-table preparation. Organ will be treated with continuous HOPE until transplant. Organ perfusion will be continuously monitored. Minimal perfusion time will be 2 hours for kidneys.
No Intervention: Kidney-Static Cold Storage
Kidneys undergoing SCS will be stored in sterile organ bags with Celsior or University of Wisconsin solution and cooled in ice.
Experimental: Liver-Hypothermic oxygenated
Belzer machine perfusion solution at 4°C-10°C in sterile conditions and continuous oxygenation (partial pressure of oxygen=500-600 mmHg) will be used for perfusion 3000 ml for livers.
Device: Liver-Hypothermic oxygenated

Liver perfusion will be performed through the portal vein at a 5 mmHg pressure.

Flow, pressure and temperature will be monitored and registered on a Universal Serial Bus (USB) memory system during organ perfusion. Gas analysis of the effluent perfusate will be accomplished at the start of perfusion (T0) then every 30 minutes. Two perfusate samples will be collected at the beginning and at the end of perfusion to rule out bacterial or fungal contamination.

HOPE will start by flushing the organ at low flow values (30 ml/min) with new oxygenated perfusion fluid during back-table preparation. Organ will be treated with continuous HOPE until transplant. Organ perfusion will be continuously monitored. Minimal perfusion time will be 1 hour for livers.
No Intervention: Liver-Static Cold Storage
Livers undergoing SCS will be stored in sterile organ bags with Celsior or University of Wisconsin solution and cooled in ice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver Transplant - Early allograft dysfunction (EAD)
Time Frame: 0-30 days after procedure
Present/Non present
0-30 days after procedure
Kidney Transplant- Delayed graft function (DGF)
Time Frame: 0-30 days after procedure
Present/Non present
0-30 days after procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Liver and Kidney surgical complications
Time Frame: 0-6 months after procedure
Present/Non present
0-6 months after procedure
Liver and Kidney graft function at 6 and 12 months
Time Frame: 0-12 months after procedure
Functioning/non functioning
0-12 months after procedure
Patient survival at 6 and 12 months
Time Frame: 0-12 months after procedure
Alive/Death
0-12 months after procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Bologna

Investigators

  • Principal Investigator: Matteo Ravaioli, PhD, University of Bologna S.Orsola-Malpighi Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 21, 2018

Primary Completion (Anticipated)

December 1, 2019

Study Completion (Anticipated)

December 1, 2021

Study Registration Dates

First Submitted

February 5, 2019

First Submitted That Met QC Criteria

February 6, 2019

First Posted (Actual)

February 12, 2019

Study Record Updates

Last Update Posted (Actual)

September 27, 2019

Last Update Submitted That Met QC Criteria

September 25, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RF-2016-02364732

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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