Hepatocellular InjuryNCT01317342
Hypothermic Oxygenated Perfusion (HOPE) of Human Liver Grafts
A study testing Hypothermic oxygenated perfusion (HOPE) in people with Hepatocellular Injury, run by University of Zurich at 2 sites in Switzerland.
Trial summary
The purpose of this study is, in a randomized trial, to test a newly developed machine perfusion technique of human liver allografts before transplantation. Ischemia-reperfusion injury is universal in organ transplantation and leads to varying degrees of graft dysfunction. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hepatocellular Injury
- What is being tested?
- Hypothermic oxygenated perfusion (HOPE)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 179 participants
- Where
- 2 sitesSwitzerland
- Study dates
- Apr 2015to 30 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (≥18 years) patients with acute liver failure or liver cirrhosis (CHILD A, B or C) and/ or malignant liver tumors requiring liver transplantation
- Whole liver graft
- Signed informed consent
Who cannot join
- Split graft
- Living donor liver transplantation
- Grafts donated after cardiac arrest (DCD grafts)
- Domino transplantation
- Combined liver transplant
- Cold storage > 15h
- acute and unexpected medical contraindication
Trial locations and contacts
2 sites in 1 country.
Switzerland2 sites
University Hospital of Zurich
Zurich, 8091
University of Zurich
Zurich, 8091
About this study
Official title: A Randomized Multicenter Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation
The purpose of this study is, in a randomized trial, to test a newly developed machine perfusion technique of human liver allografts before transplantation.
Ischemia-reperfusion injury is universal in organ transplantation and leads to varying degrees of graft dysfunction. Despite this fact, the preservation method in organ transplantation has been left unchanged for many years and remains simple static cold storage. Given the scarce donor supply, an increasing number of so called marginal or extended criteria donor organs have been used for liver transplantation, grafts which were previously rarely considered. In addition, allocation policy has changed in many countries, and livers are currently often distributed by the severity of the recipient's disease. As a result, transplant candidates present sicker, with higher MELD (Model for end stage liver disease) scores, at the time of transplant,and the risk of graft dysfunction or even failure due to reperfusion injury is high after the use of marginal livers in sick recipients.
Read more
Machine liver perfusion techniques have been significantly improved during the past decade to decrease reperfusion injury, and a number of promising results show beneficial effects in various animal transplant models by either normothermic or hypothermic oxygenated continuous liver perfusion. These techniques generally require machine liver perfusion immediately after organ procurement. However, continuous perfusion has several drawbacks, including major logistic efforts and risk of organ damage during perfusion and transport.
Our group, therefore, focused on the practicability of machine liver perfusion. We developed an endischemic hypothermic oxygenated perfusion (HOPE) concept through the portal vein only. This technique can be easily applied in the operation room shortly before transplantation of the recipient, thus after organ transport and back table preparation.
Recently, the beneficial effect of a similar approach has been confirmed in human liver grafts by a phase I non randomized trial. These results prove feasibility and safety of an endischemic hypothermic machine perfusion approach and warrant further randomized studies.
Read the detailed description
The study consists on two groups, a perfusion group and a control group. Patients on the waiting list for liver transplantation with proven written consent will be recruited and randomized during organ procurement. Randomization will be performed by computer (secutrial). Perfusion will be started in the operation room after regular organ procurement, transport and back table preparation. The perfusion procedure will not delay the implantation due to the fact that recipient hepatectomy usually takes 2 hours. During this procedure, hypothermic oxygenated perfusion (HOPE group) for one hour will be performed vs continued cold storage (Control group).
We will use commercially available and approved IGL solution (Institut George Lopez) as perfusate for machine perfusion.
Subjects will be followed for one year after transplantation.
10 European centers are participating in this study, Randomization is stratified by center.
- Conditions
- Hepatocellular Injury
- Being tested
- Hypothermic oxygenated perfusion (HOPE)
- Keywords
- liver transplantation, machine liver perfusion, extended criteria liver grafts, donation after cardiac death, hypothermic machine liver perfusion, liver reperfusion injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypothermic oxygenated perfusion (HOPE)Device
Application of HOPE for 1 hour, perfusion rate 150-300 ml/min, pressure controlled, perfusion pressure < 3 mm Hg, perfusion route portal vein, recirculating system, perfusion volume 2 L, perfusate Institute George Lopez solution (IGL-1), perfusate temperature 4-6 °C, perfusate oxygenation 150-200 mm Hg
| Study group | Role | What they receive |
|---|---|---|
| Hypothermic oxygenated perfusion (HOPE) | Active comparator | Application of HOPE for 1 hour Receives: Device: Hypothermic oxygenated perfusion (HOPE) |
| Control group: no intervention | No intervention | Conventional cold storage (IGL-1) |
What is being measured
The primary outcome is the main question the study is designed to answer.
major complications after liver transplantation
post transplant complication Clavien >= III within 1 year after transplant
Measured: During the first year postoperatively
Secondary outcomes (4)
Laboratory parameters post transplant
Serum concentrations of bilirubin, AST, ALT, INR; Factor V
Measured: during first week, & 3,6,9,12 months
Cholangiopathy
Biliary complications
Measured: during 12 months after transplant
hospital stay, ICU stay
length of hospital and ICU stay after liver transplantation
Measured: during 12 months after transplant
Patient and graft survival
one year patient and graft survival
Measured: during 12 months after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2011 (estimated)
- Study startApr 2015
- Primary completion30 Aug 2020
- Study completion30 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular InjuryStudies of the same condition, open and under way.
- More trials run by University of ZurichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 179 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philipp Dutkowski, Principal investigator, Department of Surgery and Transplantation, University Hospital Zurich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01317342
- Sponsor's protocol ID
- 2011-0079
- Status last verified
- Mar 2021
- First submitted
- 10 Mar 2011
- Last updated
- 25 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA, Dutkowski P. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009 Nov;250(5):674-83. doi: 10.1097/SLA.0b013e3181bcb1ee.
PubMed 19806056Dutkowski P, de Rougemont O, Clavien PA. Machine perfusion for 'marginal' liver grafts. Am J Transplant. 2008 May;8(5):917-24. doi: 10.1111/j.1600-6143.2008.02165.x.
PubMed 18416733Dutkowski P, Furrer K, Tian Y, Graf R, Clavien PA. Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor. Ann Surg. 2006 Dec;244(6):968-76; discussion 976-7. doi: 10.1097/01.sla.0000247056.85590.6b.
PubMed 17122622Schlegel A, Mueller M, Muller X, Eden J, Panconesi R, von Felten S, Steigmiller K, Sousa Da Silva RX, de Rougemont O, Mabrut JY, Lesurtel M, Cerisuelo MC, Heaton ND, Allard MA, Adam R, Monbaliu D, Jochmans I, Haring MPD, Porte RJ, Parente A, Muiesan P, Kron P, Attia M, Kollmann D, Berlakovich G, Rogiers X, Petterson K, Kranich AL, Amberg S, Mullhaupt B, Clavien PA, Dutkowski P. A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation. J Hepatol. 2023 Apr;78(4):783-793. doi: 10.1016/j.jhep.2022.12.030. Epub 2023 Jan 19.
PubMed 36681160
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Multicenter Study on the Effects of Hypothermic Oxygenated Perfusion (HOPE) on Human Liver Grafts Before Transplantation
- ClinicalTrials.gov ID
- NCT01317342
- Acronym / sponsor ID
- 2011-0079
- Conditions
- Hepatocellular Injury
- Keywords
- liver transplantation, machine liver perfusion, extended criteria liver grafts, donation after cardiac death, hypothermic machine liver perfusion, liver reperfusion injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 179 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- 30 Aug 2020 (actual)
- Study completion
- 30 Aug 2020 (actual)
- First posted
- 17 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is, in a randomized trial, to test a newly developed machine perfusion technique of human liver allografts before transplantation.
Ischemia-reperfusion injury is universal in organ transplantation and leads to varying degrees of graft dysfunction. Despite this fact, the preservation method in organ transplantation has been left unchanged for many years and remains simple static cold storage. Given the scarce donor supply, an increasing number of so called marginal or extended criteria donor organs have been used for liver transplantation, grafts which were previously rarely considered. In addition, allocation policy has changed in many countries, and livers are currently often distributed by the severity of the recipient's disease. As a result, transplant candidates present sicker, with higher MELD (Model for end stage liver disease) scores, at the time of transplant,and the risk of graft dysfunction or even failure due to reperfusion injury is high after the use of marginal livers in sick recipients.
Machine liver perfusion techniques have been significantly improved during the past decade to decrease reperfusion injury, and a number of promising results show beneficial effects in various animal transplant models by either normothermic or hypothermic oxygenated continuous liver perfusion. These techniques generally require machine liver perfusion immediately after organ procurement. However, continuous perfusion has several drawbacks, including major logistic efforts and risk of organ damage during perfusion and transport.
Our group, therefore, focused on the practicability of machine liver perfusion. We developed an endischemic hypothermic oxygenated perfusion (HOPE) concept through the portal vein only. This technique can be easily applied in the operation room shortly before transplantation of the recipient, thus after organ transport and back table preparation.
Recently, the beneficial effect of a similar approach has been confirmed in human liver grafts by a phase I non randomized trial. These results prove feasibility and safety of an endischemic hypothermic machine perfusion approach and warrant further randomized studies.
Detailed description
The study consists on two groups, a perfusion group and a control group. Patients on the waiting list for liver transplantation with proven written consent will be recruited and randomized during organ procurement. Randomization will be performed by computer (secutrial). Perfusion will be started in the operation room after regular organ procurement, transport and back table preparation. The perfusion procedure will not delay the implantation due to the fact that recipient hepatectomy usually takes 2 hours. During this procedure, hypothermic oxygenated perfusion (HOPE group) for one hour will be performed vs continued cold storage (Control group).
We will use commercially available and approved IGL solution (Institut George Lopez) as perfusate for machine perfusion.
Subjects will be followed for one year after transplantation.
10 European centers are participating in this study, Randomization is stratified by center.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hypothermic oxygenated perfusion (HOPE) | Active comparator | Device: Hypothermic oxygenated perfusion (HOPE)Application of HOPE for 1 hour |
| Control group: no intervention | No intervention | –Conventional cold storage (IGL-1) |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult (≥18 years) patients with acute liver failure or liver cirrhosis (CHILD A, B or C) and/ or malignant liver tumors requiring liver transplantation
- Whole liver graft
- Signed informed consent
Key exclusion criteria (7 listed)
- Split graft
- Living donor liver transplantation
- Grafts donated after cardiac arrest (DCD grafts)
- Domino transplantation
- Combined liver transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hypothermic oxygenated perfusion (HOPE)Application of HOPE for 1 hour, perfusion rate 150-300 ml/min, pressure controlled, perfusion pressure < 3 mm Hg, perfusion route portal vein, recirculating system, perfusion volume 2 L, perfusate Institute George Lopez solution (IGL-1), perfusate temperature 4-6 °C, perfusate oxygenation 150-200 mm Hg | Device | Hypothermic oxygenated perfusion (HOPE) |
Primary outcome
major complications after liver transplantation
Time frame: During the first year postoperatively
post transplant complication Clavien >= III within 1 year after transplant
4 secondary outcomes
Laboratory parameters post transplant
Time frame: during first week, & 3,6,9,12 months
Cholangiopathy
Time frame: during 12 months after transplant
hospital stay, ICU stay
Time frame: during 12 months after transplant
Patient and graft survival
Time frame: during 12 months after transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2021.
- Background: PubMed 19806056de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA, Dutkowski P. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009 Nov;250(5):674-83. doi: 10.1097/SLA.0b013e3181bcb1ee.
- Background: PubMed 18416733Dutkowski P, de Rougemont O, Clavien PA. Machine perfusion for 'marginal' liver grafts. Am J Transplant. 2008 May;8(5):917-24. doi: 10.1111/j.1600-6143.2008.02165.x.
- Background: PubMed 17122622Dutkowski P, Furrer K, Tian Y, Graf R, Clavien PA. Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor. Ann Surg. 2006 Dec;244(6):968-76; discussion 976-7. doi: 10.1097/01.sla.0000247056.85590.6b.
- Derived from this study: PubMed 36681160Schlegel A, Mueller M, Muller X, Eden J, Panconesi R, von Felten S, Steigmiller K, Sousa Da Silva RX, de Rougemont O, Mabrut JY, Lesurtel M, Cerisuelo MC, Heaton ND, Allard MA, Adam R, Monbaliu D, Jochmans I, Haring MPD, Porte RJ, Parente A, Muiesan P, Kron P, Attia M, Kollmann D, Berlakovich G, Rogiers X, Petterson K, Kranich AL, Amberg S, Mullhaupt B, Clavien PA, Dutkowski P. A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation. J Hepatol. 2023 Apr;78(4):783-793. doi: 10.1016/j.jhep.2022.12.030. Epub 2023 Jan 19.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philipp Dutkowski principal investigator
Department of Surgery and Transplantation, University Hospital Zurich
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hypothermic oxygenated perfusion (HOPE) in people with Hepatocellular Injury, run by University of Zurich at 2 sites in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
major complications after liver transplantation (time frame: During the first year postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01317342, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2021.