Plain English Summary
Background and study aims
Patients with end-stage liver disease can be treated with a liver transplant. A marginal graft is a donated organ with an increased risk for poor function or failure. The quality of marginal donor grafts can be improved by using different methods of organ preservation or techniques to revitalise the tissue before transplantation. The side effects of extended storage times, for instance, can be reduced with a short period of hypothermic (low temperature) oxygenated machine perfusion. The protective effect of this procedure can be improved with a limited and slow proceeding increasing of the temperature during oxygenated machine perfusion (controlled oxygenated rewarming). This results in a slower and more gentle activation of cell metabolism and reduces the risk of rewarming injury affecting cold stored tissue upon abrupt warming up during reperfusion. A series of individual treatments have been recently performed on marginal livers without complications and resulted in apparently good graft recovery after transplantation. The aim of this study is to test whether controlled oxygenated rewarming by machine perfusion improves the graft quality of donor livers.
Who can participate?
Patients aged over 18 with end-stage liver disease who are listed for liver transplantation
What does the study involve?
Donor livers are randomly allocated to the control group or the treatment group. The control group donor livers do not receive any experimental treatment before implantation. The treatment group donor livers are subjected to 2 hours of temperature controlled oxygenated machine perfusion before implantation, starting with a perfusion temperature of 10°C which is slowly increased up to 20°C. All patients are observed for 7 days following transplantation on a daily basis. Follow up includes additional observations on the day of discharge and 3 months after transplantation. Patients are followed until 3 months after the last patient joins the study and are asked to attend clinical routine follow up after the end of the study.
What are the possible benefits and risks of participating?
Possible benefits are an expected reduction of reperfusion injury of the graft and an improved early recovery of liver function after transplantation. The planned treatment has been tested in animals as well as in an earlier study and is considered to be a safe procedure.
Where is the study run from?
University of Duisburg-Essen (Germany)
When is the study starting and how long is it expected to run for?
October 2016 to October 2019
Who is funding the study?
German Research Foundation (Germany)
Who is the main contact?
Prof. Andreas Paul
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
-
Study information
Scientific title
Controlled Oxygenated Rewarming as Adjunct in Liver transplantation (CORAL) of human allografts from extended criteria donors (ECD): a prospective randomized controlled trial
Acronym
CORAL
Study hypothesis
Study hypothesis:
1. Controlled oxygenated rewarming of the cold preserved liver graft prior to warm repefusion will mitigate rewarming/reperfusion injury upon liver transplantation
2. Functional data obtained during ex-situ machine perfusion will help to evaluate graft integrity prior to transplantation
Ethics approval
Ethics Committee, Medical Faculty, University of Duisburg-Essen (Ethik Kommission der Medizinischen Fakultät der Universität Duisburg-Essen), 29/11/2016, ref: 16-7110 BO
Study design
Single-center randomized controlled clinical pilot study with two parallel arms
Primary study design
Interventional
Secondary study design
Randomised parallel trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Preservation and implantation of liver grafts
Intervention
Randomisation: 1:1 block randomisation. The donor liver is randomized. Only patients who had given informed consent to participate in the study will be included in the randomization and the study.
Control study arm: everything will be left according to clinical standards without any experimental treatment.
Experimental study arm: Livers will be put on a CE-certified organ perfusion machine (Liver Assist®, Fa. Organ Assist, The Netherlands) and machine perfusion is started via hepatic artery and portal vein in a closed circuit with Belzer machine perfusion solution. Perfusate will be oxygenated to a pO2 > 500mmHg via two oxygenators included in arterial and portal circuits and temperature of the perfusate will be increased slowly over time to reach a steady state of 20°C afte 60 min. Total perfusion time will be 90 min or slightly longer, if the recipient preparation time will exceed the minimal perfusion time of 90 min (for further details see: Hoyer DP et al. Controlled Oxygenated Rewarming of Cold Stored Livers Prior to Transplantation: First Clinical Application of a New Concept. Transplantation. 2016;100:147-52).
All patients are observed for 7 days following transplantation on a daily basis. Follow up includes additional observations on the day of discharge and 3 months after transplantation. Patients are followed until 3 months after the last patient is randomised for this trial and are asked to attend clinical routine follow up subsequent to termination of the study.
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
Serum peak value of aspartate aminotransferase-AST during the first 3 days after transplantation
Secondary outcome measures
1. Death/6 month graft survival
2. Re-transplantation within 6 months after implantation
3. Time of stay in intensive care unit
4. Early Allograft Dysfunction (EAD) according to Olthoff (bilirubin>10mg/dl or INR >1.6 at POD 7, or peak-AST > 2000 U/L during first week after transplantation
5. Hepatic tissue perfusion measured 1h after revascularisation
All patients are observed for seven days following transplantation on a daily basis. Follow up includes additional observations on the day of discharge and 3 month after transplantation. Patients are followed until 3 months after the last patient is randomized for this trial and are asked to attend clinical routine follow up subsequent to termination of the study.
Overall trial start date
01/10/2016
Overall trial end date
01/10/2019
Reason abandoned (if study stopped)
Lack of funding/sponsorship
Eligibility
Participant inclusion criteria
Enhanced criteria donor according to recommendations of the German Medical Chamber:
1. Donor age > 65 years
2. Intensive therapy including assisted ventilation > 7 days
3. Obesity of donor (BMI > 30)
4. Serum Na > 165 Mol/l
5. GOT GPT > 3 x of normal
6. S-Bilirubin > 3 mg/dl
7. Liver steatosis (histologically proven) > 40%
Patient:
1. Patient suffering from end-stage liver disease
2. Listed for liver transplantation
3. Signed informed consent
4. Age >18 years
5. Living in Germany
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
20 per group
Participant exclusion criteria
1. HU-listed
2. Re-transplantation
3. Simultaneous participation in other preservation trial
4. HIV-positive
5. MELD score >25
Recruitment start date
31/07/2017
Recruitment end date
31/07/2017
Locations
Countries of recruitment
Germany
Trial participating centre
University of Duisburg-Essen
Essen
45122
Germany
Funders
Funder type
Government
Funder name
Deutsche Forschungsgemeinschaft
Alternative name(s)
German Research Foundation, German Research Association, DFG
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
Location
Germany
Results and Publications
Publication and dissemination plan
Dissemination of the results is planned by publication in a high-impact peer reviewed journal.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/10/2020
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list