Clinical trial NCT03837197: Clinical Trial of New Hypothermic Oxygenated Perfusion System Versus Static Cold Storage
Official title: Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol of a Randomised Single Center Clinical Trial of Hypothermic Oxygenated Perfusion Versus Static Cold Storage
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Diseases
Kidney Diseases
Keywords: donors and donation
Extended criteria donor
Organ perfusion and preservation
Liver transplantation
Kidney transplantation
Preservation injury
Ischemia reperfusion injury
Lead sponsor: University of Bologna
Sponsor class: OTHER
First posted: 2019-02-12
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liver Transplant - Early allograft dysfunction (EAD)
timeFrame: 0-30 days after procedure
measure: Kidney Transplant- Delayed graft function (DGF)
timeFrame: 0-30 days after procedure
Secondary outcomes:
measure: Liver and Kidney surgical complications
timeFrame: 0-6 months after procedure
measure: Liver and Kidney graft function at 6 and 12 months
timeFrame: 0-12 months after procedure
measure: Patient survival at 6 and 12 months
timeFrame: 0-12 months after procedure
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Azienda Ospedaliera di Bologna - Policlinico S. Orsola Malpighi
Study officials:
affiliation: University of Bologna S.Orsola-Malpighi Hospital
name: Matteo Ravaioli, PhD
role: PRINCIPAL_INVESTIGATOR
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