Plain English Summary
Background and study aims
The life of many people strictly depends on a new liver. Unfortunately, there are not enough organs for all potential recipients on the waiting list. Livers of lower quality with a higher risk of functional impairment after transplantation therefore have to be used. The aim is therefore to improve the quality and function of such livers. Hypothermic oxygenated perfusion (HOPE) is organ perfusion with a cold perfusion solution with a lot of oxygen. Following routine liver transport in the cold (standard cold storage), livers undergo a short, cold perfusion for 1-2 hours before implantation. The machine used for this has been introduced into the field of liver transplantation and is used in many centres worldwide. A short, cold and oxygenated liver perfusion before transplantation improves the function of the liver in the recipient. These results have been confirmed internationally. The aim of this study is to improve liver function after transplantation by using a short and cold machine perfusion and analyse outcomes and complications after liver transplantation.
Who can participate?
Patients aged 18 or above who are receiving a liver transplant
What does the study involve?
Livers are randomly allocated into two groups to undergo either conventional cold storage or cold storage plus HOPE before implantation. The liver recipients are followed up to assess complications, liver function, length of hospital and ICU stay, and patient and transplant survival at 1 year.
What are the possible benefits and risks of participating?
Participation may improve the function of the new liver and the results will help liver recipients in the future, as more patients will receive a new liver with a better function, outcome and survival in the future. The perfusion solution is produced synthetically, sterile and has not been retrieved from another living organism. Participants are therefore not exposed to a higher risk for transmission of HIV or hepatitis virus infections. During and after the transplant procedure, several blood tests and liver biopsies (samples) are regularly necessary. There are no changes from the standard procedure after liver transplantation during participation in this study. The medical treatment including immunosuppression is not influenced by the study. All liver recipients get standard immunosuppression, with or without participation in the study. The overall risk for participants is very small. Occurrence of unexpected risks is unlikely but cannot be completely excluded. More than 120 livers have been transplanted after this perfusion technique worldwide (in Switzerland, USA, Italy and Netherlands), where no specific unexpected side effects have been reported yet.
Where is the study run from?
The study takes place at University Hospital Zurich (Switzerland) and 8-10 other centres in Europe, for example in Birmingham (QEHB), London (King’s College Hospital) and Edinburgh (UK).
When is the study starting and how long is it expected to run for?
April 2016 to July 2019
Who is funding the study?
Swiss National Science Foundation (Switzerland)
Who is the main contact?
Dr Andrea Schlegel
Trial website
Additional identifiers
EudraCT number
2016-002540-16
ClinicalTrials.gov number
NCT01317342
Protocol/serial number
2011-0079/4
Study information
Scientific title
Hypothermic oxygenated perfusion (HOPE) of human liver grafts before transplantation - A multicenter, randomized controlled trial
Acronym
HOPE study
Study hypothesis
The purpose of this study is, in a phase II randomized trial, to test a newly developed machine perfusion technique of human liver allografts before transplantation. Significance of planned research: Late biliary injury and graft loss remain a major problem in the era of sick liver transplant recipients and marginal donors. Machine liver perfusion techniques have been recognized as potentially protective, but are still not in use in human liver transplantation, because of low practicability and lack of prospective human studies. The suggested study will demonstrate, for the first time worldwide, the effect of an easy and applicable perfusion technique in human liver grafts. The trialists postulate, therefore, a high acceptance rate among transplant surgeons. In case of convincing success, it can be applied at low cost and low resources in any center worldwide.
Ethics approval
Kantonal Ethical Commission Zurich, Switzerland, 06/09/2011, ref: KEKZH2011-0079(KEK-ZH-Nr.2011-0079/4
Study design
Multicenter randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
See additional files
Condition
Liver transplantation
Intervention
Randomization will be performed at the time of liver acceptance. This is usually also the time when the liver recipient is admitted to hospital. The liver will be randomized by the local investigator or the trial coordinator using an online randomization tool. A computer-generated list of random assignments (block randomization per center (www.randomizer.at) is prepared in advance. Hence, concealed allocation will not be possible. The timepoint for randomization will be at the end of procurement to assure a minimum dropout of cases. The procurement team will call the local or principal investigator, who coordinates the randomization in that center. The randomization list from the randomizer has been incorporated into the newly developed eCRF. All personnel involved in randomization will be trained in the use of the online randomization by the Project Leader or the Principal Investigator of each site.
Liver grafts from brain death donors (DBD) will be randomly divided in two groups, receiving either conventional cold storage (n=85) according to standard criteria of organ preservation or cold storage plus subsequent hypothermic oxygenated perfusion (HOPE), performed ex-situ with the liver assist device, before implantation (n=85).
Follow up of each included patient will be 12 months.
Intervention type
Device
Phase
Phase II
Drug names
Primary outcome measure
Major postoperative complications (Clavien Grade > or =III), using the established Clavien classification supported by a recently developed comprehensive complication index (CCI). Complications are summarized in the eCRF from the time of transplantation until 1 year after liver transplantation, which is the end of follow up. In the eCRF complications are monitored during hospital stay, at 3 and 6 and 9 and 12-month outpatient controls after liver transplantation.
Secondary outcome measures
1. Plasma AST and ALT, measured 6 and 12 hours after OLT, and at day 1-7 postoperatively to determine the area under the curve (AUC)
2. Postoperative liver function measured by INR (plasma, at day 1-7)
3. Intra- and extrahepatic biliary complications within the first year after liver transplantation, assessed by serum cholestasis parameters (Bilirubin, Gammaglutamyltransferase, Alkaline Phosphatase) every 3 months and liver MRI including an MCRP 12 months after liver transplantation
4. Length of hospital and ICU stay after transplantation
5. Patient and graft survival at 1 year
Overall trial start date
01/04/2016
Overall trial end date
31/07/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Candidates for liver transplantation
2. Aged 18 or above
3. Receiving a whole liver graft
4. Full consent for the study
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
170
Participant exclusion criteria
1. DCD livers
2. Split grafts
3. Living donor livers
4. Combined grafts
5. Domino liver transplantations
6. Cold storage of more than 12 hrs
Recruitment start date
01/04/2016
Recruitment end date
01/05/2018
Locations
Countries of recruitment
France, Germany, Netherlands, Romania, Spain, Switzerland, United Kingdom
Trial participating centre
Queen Elizabeth Hospital Birmingham
B15 2TH
United Kingdom
Trial participating centre
University Hospital Zurich
8091
Switzerland
Trial participating centre
King's College Hospital
London
SE5 9RS
United Kingdom
Trial participating centre
Royal Infirmary of Edinburgh
EH16 4SA
United Kingdom
Trial participating centre
Hospital Universitario “Reina Sofia”
Cordoba
14004
Spain
Trial participating centre
University of Medicine “Carol Davila”
Fundeni Clinical Institute
Bucharest
030167
Romania
Trial participating centre
Klinik für Allgemeine und Transplantationschirurgie - University Hospital Essen
45147
Germany
Trial participating centre
Universitaire Ziekenhuizen Leuven
Abdominal Transplant Surgery
B-3000
Belgium
Trial participating centre
Erasmus Medical Centre
Rotterdam
3015 CE
Netherlands
Trial participating centre
University Medical Centre Groningen
9713 GZ
Netherlands
Sponsor information
Organisation
University Hospital Zurich
Sponsor details
Raemistrasse 100
Zurich
8091
Switzerland
+41 (0)442 551 111
andrea.schlegel@usz.ch
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Research organisation
Funder name
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Alternative name(s)
Swiss National Science Foundation, Fonds National Suisse de la Recherche Scientifique, Fondo Nazionale Svizzero per la Ricerca Scientifica, Fonds National Suisse, Fondo Nazionale Svizzero, Schweizerischer Nationalfonds, SNSF, FNS, SNF
Funding Body Type
private sector organisation
Funding Body Subtype
Trusts, charities, foundations (both publically funded and privately funded)
Location
Switzerland
Results and Publications
Publication and dissemination plan
Publication following interim analysis when 40 patients have been randomized into the study, and final publication when the study has been completed. Publication is expected in summer/autumn 2019.
IPD sharing statement
Participants data will be collected in an electronic case report form (eCRF) and will be available for a few investigators per centre and the sponsor. Importantly, investigators will exclusively have access to participants data from their own centre. When eCRF training has been completed successfully, the personal password and login details are provided by the clinical trial centre in Zurich, Switzerland (Sponsor, leading trial coordinator) just after the centre received the ethical approval prior to start with the inclusion of patients. Participants give consent to use their data after transplantation, which will exclusively be used for the trial and are not accessible for any other purpose. Data are completely anonymised and trial numbers are allocated to each participant by the eCRF system automatically.
Intention to publish date
01/09/2019
Participant level data
Stored in repository
Basic results (scientific)
Publication list
Publication citations
Additional files
- ISRCTN15527114_PIS_17Aug17.pdf Uploaded 07/12/2017