Viability Testing and Transplantation of Marginal Livers

Not Applicable

Completed

• Conditions: Liver Transplantation
• Interventions: Device: OrganOx metra

• Registration Number: NCT02740608
• Lead Sponsor: University of Birmingham

Brief Summary

This study is designed to determine if a rejected liver is viable using normothermic machine liver perfusion (NMLP). It aims to

1. establish the suitability of livers which have been declined by all UK liver transplant centres by monitoring their function on the NMLP machine; and,

2. transplant the liver if its function on the machine is satisfactory allowing it to be transplanted.

Detailed Description

Deaths from liver disease have soared by 40 per cent in a decade and continue to rise. Liver transplantation is a highly successful treatment of end stage liver disease, fulminant hepatic failure and early stage primary liver cancer. The demand for donor livers for transplantation greatly exceeds supply and approximately 20% of patients die whilst awaiting transplantation. Normothermic machine liver perfusion (NMLP) is a novel technique developed for the purposes of organ preservation, which we have also found allows monitoring of liver graft function ex-vivo by measuring bile production, whilst permitting objective assessment of liver biochemistry and blood flow. The OrganOx metra, the NMLP device we are using, is CE marked but is not currently licensed for this particular use and the livers will not be transported using this device (which the CE mark currently covers). The device will be used at a particular site (in this case University Hospitals Birmingham) and after a period of static cold storage during which the liver will be transported to the hospital for testing on the device. The study population will be extended criteria donor livers, rejected for transplantation by all UK centres, which are then found to be functioning during perfusion and transplanted into "medium to low-risk" liver transplant recipients. VITTAL is an open label, non-randomised, prospective, single arm, 2-part trial the objectives of which are to:

* Further validate liver viability assessment criteria

* Perform the phase 2 study transplanting successfully resuscitated "rejected" livers

* Establish the feasibility of NMLP as a means to increase the number of transplantable livers.

* Identify novel biomarkers that are indicative of liver quality and function In terms of intervention, the procurement and transplantation of the organs will follow the current standard of care. The only deviation from the current standard will be the normothermic perfusion of organs following static cold storage in order to test their ability to function. This study is based on results from a 5-case pilot series which transplanted low-risk recipients with organs that had been rejected for transplantation but had been shown to function on the normothermic machine perfusion device. This work is currently in the process of being published. The main risk would be the transplantation of a non-functioning graft (resulting in a case of primary non-function that could result in re-transplantation or patient death.) Based on our pre-clinical research and clinical pilot series we believe the criteria we have identified that indicate organ function are stringent and significantly reduce this risk.

Study Timeline

• Study First Submitted: 2016-04-12
• Study First Submitted QC: 2016-04-12
• Study First Posted: 2016-04-15
• Study Start: 2016-10-06
• Primary Completion: 2018-05-08
• Study Completion: 2020-03
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-23
• Last Update Posted: 2022-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Liver transplantation	OrganOx metra	All Participants will receive liver transplantation using the OrganOx metra device

Primary Outcome Measures

Name	Time	Method
Use of NMLP to identify the proportion of transplantable liver grafts from the currently rejected donor organ pool.	Approximately 6 hours	Decision point of using graft in patient transplantation
Patient survival	90 days	Achievement of successful transplantation of previously rejected donor liver following viability testing using NMLP

Secondary Outcome Measures

Name	Time	Method
Physiological response to reperfusion of the perfused grafts	Approximately 6 hours	Assess the physiological response to reperfusion of the perfused grafts by; • Post-reperfusion syndrome (Defined as a decrease in mean arterial pressure (MAP) of more than 30% from the baseline value for more than one minute during the first five minutes after reperfusion (assessed in the context of inotrope use)
Liver graft function	12 month	Assess the liver graft function following transplantation (by incidence of primary non-function, and early allograft dysfunction) by; * Liver function tests; * 90-day graft survival; * 12-month patient and graft survival The secondary endpoints and other outcome measures will be compared with a contemporary matched recipient group
Morbidity associated with receipt of extended criteria graft	90 days	Assess morbidity associated with receipt of extended criteria graft that had previously been rejected by; * Adverse event rates and severity; * Requirement of renal replacement therapy; * Incidence of biliary complications; * Incidence of vascular complications; * Biopsy-proven acute rejection; * Reoperation rate; * Length of intensive therapy unit stay; * Length of hospital stay

Trial Locations

Locations (1)

UHBFT - Queen Elizabeth Hospital, Birmingham; 🇬🇧 Birmingham, United Kingdom