Liver FailurePhase 3DHOPE-DCDNCT02584283
Dual Hypothermic Oxygenated Perfusion of DCD Liver Grafts in Preventing Biliary Complications After Transplantation
A Phase 3 study testing Dual hypothermic oxygenated perfusion, Liver Assist® and Perfusion fluid in people with Liver Failure and End Stage Liver Disease, run by Robert J. Porte at 6 sites in 3 countries.
Trial summary
Rationale: Recent publications report good results of controlled donation after circulatory death (DCD) Maastricht category III liver transplantation when strict donor-recipient matching is applied and ischemia times are kept to a minimum. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Liver Failure, End Stage Liver Disease, Biliary Tract Diseases
- What is being tested?
- Dual hypothermic oxygenated perfusion, Liver Assist® and Perfusion fluid
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 157 participants
- Where
- 6 sitesin 3 countries
- Study dates
- Jan 2016to Jan 2020
- Phase
- Phase 3
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (≥ 18 years old)
- Signed informed consent
- Willing and able to attend follow-up examinations
- Donor liver graft from a controlled donation after circulatory death (Maastricht category III)
- Donors with a body weight ≥40 kg
Who cannot join
- Simultaneous participation in another clinical trial that might possibly influence this trial
- Mental conditions rendering the subject incapable to understand the nature, scope and consequences of the trial
- Listed for liver transplantation due to fulminant liver failure or retransplantation because of primary non-function
- Recipient positive test for HIV
- Donor positive for HIV antigen, hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody
- Simultaneous transplantation of another organ
- Patients with contra-indications for MRCP (i.e. pacemaker)
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
Netherlands3 sites
University Medical Center Groningen
Groningen, 9700 RB
Leiden Universtiy Medical Center
Leiden, South Holland, 2333 ZA
Erasmus Medical Center
Rotterdam, 3015 CE
Belgium2 sites
Ghent University Hospital
Ghent, De Pintelaan 185, 9000
University Hospitals Leuven
Leuven, Herestraat 49, 3000
About this study
Official title: A Multicenter Randomized Controlled Trial to Compare the Efficacy of End-ischemic Dual Hypothermic Oxygenated Perfusion With Standard Static Cold Storage of Liver Grafts Donated After Circulatory Death in Preventing Biliary Complications
Rationale: Recent publications report good results of controlled donation after circulatory death (DCD) Maastricht category III liver transplantation when strict donor-recipient matching is applied and ischemia times are kept to a minimum. However a major concern remains the high rate of biliary complications after transplantation of DCD livers. Non-anastomotic biliary strictures (NAS) occur in 29% of patients receiving a DCD graft whereas the incidence of NAS in recipients of donation after brain death (DBD) liver grafts is 11%. NAS are associated with higher morbidity and increased cost of liver transplantation. Injury to the biliary epithelium and the peribiliary vascular plexus occurring during donor warm ischemia and static cold storage (SCS) has been identified as a major risk factor for development of NAS. Machine perfusion has been proposed as an alternative strategy for organ preservation, offering the opportunity to improve the quality of the organ by providing oxygen to the graft. Experimental studies have shown that end-ischemic dual hypothermic oxygenated machine perfusion (DHOPE) helps liver grafts to recover from ischemia by restoring mitochondrial function. Moreover, DHOPE has been shown to provide better preservation of peribiliary vascular plexus of the bile ducts, which could be an important step forward in reducing the incidence of NAS after transplantation.
Objective: To study the efficacy of end-ischemic DHOPE in reducing the incidence of NAS within six months after controlled DCD (Maastricht category III) liver transplantation.
Read more
Study design: An international, multicenter, prospective, randomized, controlled, interventional, clinical trial with a two parallel arm approach (treatment/control).
Study population: Adult patients (≥18 yrs old) undergoing a liver transplantation with a liver graft procured from a controlled DCD donor (Maastricht category III) with a body weight ≥40 kg.
Intervention: In the intervention group liver grafts will be subjected to two hours of hypothermic, oxygenated perfusion at the end of SCS and before implantation. In the control group donor liver grafts will be preserved in accordance to standard practice by SCS only.
Main study parameters/endpoints: The incidence and severity of symptomatic NAS as diagnosed by an Adjudication committee (who are blinded for the group assignment) by means of magnetic resonance cholangiopancreatography (MRCP).
- Being tested
- Dual hypothermic oxygenated perfusion, Liver Assist®, Perfusion fluid, Glutathione
- Keywords
- Liver Transplantation, Donation after Circulatory Death, Machine Perfusion
- Medical subject headings
- Liver Failure, End Stage Liver Disease, Biliary Tract Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dual hypothermic oxygenated perfusionProcedure or surgery
Dual hypothermic oxygenated perfusion using the Liver Assist
Liver Assist®Device
The Liver Assist® is the device used to give the intervention dual hypothermic perfusion.
Perfusion fluidProcedure or surgery
The perfusion fluid is Belzer machine perfusion solution University of Wisconsin (Bridge-to-Life, Ltd., Northbrook, IL).
GlutathioneDrug
Glutathione in a dosage of 3 mmol/ is added to the perfusion fluid according to the intention of use of the perfusion fluid.
| Study group | Role | What they receive |
|---|---|---|
| Dual hypothermic oxygenated perfusion | Experimental | The liver is procured with a segment of supratruncal aorta. The intervention is restricted to the liver graft after arrival in the transplant center and before implantation. The donor liver is subjected to 2 hours of hypothermic oxygenated perfusion via the portal vein and the supratruncal aorta applied by the Liver Assist®. Before perfusion, the liver is flushed via the portal vein with 1 L Belzer machine perfusion solution. The perfusion is pressure controlled and set to a mean of 25 mmHg (arterial) and 5 mm Hg (portal). The perfusion fluid is 4 L Belzer machine perfusion solution with additional 3 mmol/L glutathione. The perfusion fluid is 12°C, when the temperature is set at 10°C. The oxygen flow is set at 0.5 mL/min of 100% oxygen on each of the two membrane oxygenators. Receives: Procedure: Dual hypothermic oxygenated perfusion; Device: Liver Assist®; Procedure: Perfusion fluid; Drug: Glutathione |
| Care as usual | No intervention | The donor liver is procured with a segment of 5 cm circular supratruncal aorta left attached to the coeliac trunc. The patients randomized to the control group will receive a liver graft preserved by conventional SCS without any further intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of symptomatic non-anastomotic biliary strictures (NAS)
NAS is defined as all of the following criteria:
- any irregularities or narrowing of the lumen of the intra- or extrahepatic donor bile ducts, but not at the anastomosis
- which are diagnosed by cholangiogram (preferably by MRCP)
- in the presence of a patent hepatic artery demonstrated by Doppler ultrasonography and if necessary, by computed tomography angiography
- and as assessed by the Adjudication Committee
- when imaging is indicated by clinical signs (i.e., jaundice, cholangitis) or elevation of cholestatic laboratory parameters in blood samples taken during follow-up
Measured: 6 months
Secondary outcomes (40)
Asymptomatic NAS
Asymptomatic NAS is defined as all of the following:
- irregularities or narrowing of the lumen of the intra- or extrahepatic donor bile ducts, but not at the anastomosis
- which are diagnosed by cholangiogram (preferably by MRCP)
- in the presence of a patent hepatic artery demonstrated by Doppler ultrasonography and if necessary, by computed tomography angiography
- in the absence of clinical signs (i.e., jaundice, cholangitis) or elevation of cholestatic laboratory parameters in blood samples taken during follow-up
Measured: 6 months
The severity of NAS
Severity and location of NAS is based on assessment of the images of the MRCP obtained in all patients at six months after transplantation (time window of 15 days) which will be performed based on a scoring system described by Buis et. al. And required treatment for NAS (i.e. ursodeoxycholic acid, ERCP, retransplantation)
Measured: 6 months
The location of NAS
Assessment of the images of the MRCP obtained in all patients at six months after transplantation (time window of 15 days) which will be performed based on a scoring system described by Buis et. al.
Measured: 6 months
Graft (censored and uncensored for patient death) survival
Measured: 7 days, 1, 3 , 6, and 12 months after transplantation
Patient survival
Measured: 7 days, 1, 3 , 6, and 12 months after transplantation
Primary non-function
Defined as liver failure requiring retransplantation or leading to death within seven days after transplantation without any identifiable cause such as surgical problems, hepatic artery thrombosis, portal vein thrombosis and acute rejection
Measured: 7 days
Initial poor function
Defined as a modification of the Olthoff criteria: Prothrombin time/ international normalized ratio (INR) >1.6 and or serum total bilirubin >10 mg/dL on postoperative day 7
Measured: 7 days
Biochemical analysis of graft function and ischemia-reperfusion injury
serum levels of alanine aminotransferase (ALT), AST, alkaline phosphatase (AlkP), gamma-glutamyl transferase (γGT), and total bilirubin
Measured: Postoperative day 0 - 7 and 1, 3, 6 months
Blood pressure
mm Hg
Measured: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Heart rate
beats per minute
Measured: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Vasopressor dosage
microgram/kg/min
Measured: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Length of stay
Length of initial ICU and initial hospital stay is determined in days of admission following liver transplantation. Duration of follow-up hospital stay is determined in days of hospital admission after discharge and up to six months after liver transplantation
Measured: 6 months
Postoperative complications
According to the comprehensive complication index (CCI)
Measured: 6 months
Renal function
Estimated glomerular filtration rate (eGFR) according to the 4-variable Modification of Diet in Renal Disease (MDRD) equation
Measured: day 7, and 1, 3, 6 months
Flow
ml/min
Measured: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
Pressure
mm Hg
Measured: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
Resistance
ml/min/mm Hg
Measured: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
(In selected centers) value of perfusate's pH
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's sodium
mmol/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's potassium
mmol/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's bicarbonate
mmol/l
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's lactate
mmol/l
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's alanine transaminase (ALT)
U/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's aspartate transaminase (AST)
U/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's alkaline phosphatase (AlkP)
U/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's gamma glutamyltransferase (γGT)
U/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's urea
mmol/L
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's total bilirubin
umol/l
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's thrombomodulin
pg/dl
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's high mobility group box-1 (HMBG) protein
μg/mL
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's cytochrome C
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-30e in perfusate
relative levels compared to perfusate
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-222 in perfusate
relative levels compared to perfusate
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-296 in perfusate
relative levels compared to perfusate
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA HDmiR-122 in perfusate
relative levels compared to perfusate
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA HDmiR-148a in perfusate
relative levels compared to perfusate
Measured: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
Histopathological status liver and bile ducts (in selected centers)
Measured: Within 0 to 30 minutes before perfusion, at 2 hours of perfusion, and at 1 hour after reperfusion
New onset diabetes after transplantation
- Symptoms of diabetes and random plasma glucose ≥11.1 mmol/L. Symptoms include polyuria, polydipsia, and unexplained weight loss. OR
- Fasting plasma glucose ≥7.0 mmol/L. Fasting is defined as no caloric intake for at least eight hours. OR
- Two-hour plasma glucose ≥11.1 mmol/L during an oral glucose tolerance test. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
Measured: 90 days
Costs of treatment (in selected centers)
according to the Cost and Outcome analysis of Liver Transplantation (COLT) study
Measured: within 6 months after transplantation, including transplant operation
Health related quality of life
EQ6D questionnaire
Measured: within 6 months before transplantation and 6 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study startJan 2016
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Liver FailureStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert J. Porte
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Leiden University Medical Center, Universitaire Ziekenhuizen KU Leuven, University Hospital, Ghent, King's College Hospital NHS Trust
- Responsible party
- Sponsor-investigator, Robert J. Porte, University Medical Center Groningen
- Investigators
- Robert J. Porte, MD PhD Prof, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02584283
- Sponsor's protocol ID
- DHOPE-DCD Trial
- Acronym
- DHOPE-DCD
- Status last verified
- Jan 2021
- First submitted
- 25 Sep 2015
- Last updated
- 12 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
van Rijn R, Endo C, Kucukerbil EH, Blokzijl H, Blondeel J, Cortes Cerisuelo M, Coenraad MJ, Darwish Murad S, Doukas M, Eker H, de Haas RJ, Huurman VAL, de Meijer VE, Monbaliu D, Schurink IJ, Slangen JJG, Polak WG, de Jonge J, Porte RJ. Long-term Follow-up After Hypothermic Oxygenated Machine Perfusion in DCD Liver Transplantation: Results of a Randomized Controlled Multicenter Trial (DHOPE-DCD). Ann Surg. 2025 Nov 1;282(5):717-724. doi: 10.1097/SLA.0000000000006876. Epub 2025 Aug 5.
PubMed 41082480Endo C, van Rijn R, Huurman V, Schurink I, van den Berg A, Murad SD, van Hoek B, de Meijer VE, de Jonge J, van der Hilst CS, Porte RJ. Cost-effectiveness of Dual Hypothermic Oxygenated Machine Perfusion Versus Static Cold Storage in DCD Liver Transplantation. Transplantation. 2025 Feb 1;109(2):e101-e108. doi: 10.1097/TP.0000000000005232. Epub 2024 Oct 8.
PubMed 39853733van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N, van Hoek B, Huurman VAL, Jochmans I, van Leeuwen OB, de Meijer VE, Monbaliu D, Polak WG, Slangen JJG, Troisi RI, Vanlander A, de Jonge J, Porte RJ; DHOPE-DCD Trial Investigators. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial. N Engl J Med. 2021 Apr 15;384(15):1391-1401. doi: 10.1056/NEJMoa2031532. Epub 2021 Feb 24.
PubMed 33626248de Vries Y, Berendsen TA, Fujiyoshi M, van den Berg AP, Blokzijl H, de Boer MT, van der Heide F, de Kleine RHJ, van Leeuwen OB, Matton APM, Werner MJM, Lisman T, de Meijer VE, Porte R. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial). BMJ Open. 2019 Aug 15;9(8):e028596. doi: 10.1136/bmjopen-2018-028596.
PubMed 31420387van Rijn R, van den Berg AP, Erdmann JI, Heaton N, van Hoek B, de Jonge J, Leuvenink HGD, Mahesh SVK, Mertens S, Monbaliu D, Muiesan P, Perera MTPR, Polak WG, Rogiers X, Troisi RI, de Vries Y, Porte RJ. Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial. BMC Gastroenterol. 2019 Mar 12;19(1):40. doi: 10.1186/s12876-019-0956-6.
PubMed 30866837
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Controlled Trial to Compare the Efficacy of End-ischemic Dual Hypothermic Oxygenated Perfusion With Standard Static Cold Storage of Liver Grafts Donated After Circulatory Death in Preventing Biliary Complications
- ClinicalTrials.gov ID
- NCT02584283
- Acronym / sponsor ID
- DHOPE-DCD / DHOPE-DCD Trial
- Keywords
- Liver Transplantation, Donation after Circulatory Death, Machine Perfusion
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- Robert J. PorteUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Leiden University Medical Center, Universitaire Ziekenhuizen KU Leuven, University Hospital, Ghent, King's College Hospital NHS Trust
- Study start
- Jan 2016 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 22 Oct 2015 (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.
Rationale: Recent publications report good results of controlled donation after circulatory death (DCD) Maastricht category III liver transplantation when strict donor-recipient matching is applied and ischemia times are kept to a minimum. However a major concern remains the high rate of biliary complications after transplantation of DCD livers. Non-anastomotic biliary strictures (NAS) occur in 29% of patients receiving a DCD graft whereas the incidence of NAS in recipients of donation after brain death (DBD) liver grafts is 11%. NAS are associated with higher morbidity and increased cost of liver transplantation. Injury to the biliary epithelium and the peribiliary vascular plexus occurring during donor warm ischemia and static cold storage (SCS) has been identified as a major risk factor for development of NAS. Machine perfusion has been proposed as an alternative strategy for organ preservation, offering the opportunity to improve the quality of the organ by providing oxygen to the graft. Experimental studies have shown that end-ischemic dual hypothermic oxygenated machine perfusion (DHOPE) helps liver grafts to recover from ischemia by restoring mitochondrial function. Moreover, DHOPE has been shown to provide better preservation of peribiliary vascular plexus of the bile ducts, which could be an important step forward in reducing the incidence of NAS after transplantation.
Objective: To study the efficacy of end-ischemic DHOPE in reducing the incidence of NAS within six months after controlled DCD (Maastricht category III) liver transplantation.
Study design: An international, multicenter, prospective, randomized, controlled, interventional, clinical trial with a two parallel arm approach (treatment/control).
Study population: Adult patients (≥18 yrs old) undergoing a liver transplantation with a liver graft procured from a controlled DCD donor (Maastricht category III) with a body weight ≥40 kg.
Intervention: In the intervention group liver grafts will be subjected to two hours of hypothermic, oxygenated perfusion at the end of SCS and before implantation. In the control group donor liver grafts will be preserved in accordance to standard practice by SCS only.
Main study parameters/endpoints: The incidence and severity of symptomatic NAS as diagnosed by an Adjudication committee (who are blinded for the group assignment) by means of magnetic resonance cholangiopancreatography (MRCP).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dual hypothermic oxygenated perfusion | Experimental | Procedure: Dual hypothermic oxygenated perfusion, Device: Liver Assist®, Procedure: Perfusion fluid, Drug: GlutathioneThe liver is procured with a segment of supratruncal aorta. The intervention is restricted to the liver graft after arrival in the transplant center and before implantation. The donor liver is subjected to 2 hours of hypothermic oxygenated perfusion via the portal vein and the supratruncal aorta applied by the Liver Assist®. Before perfusion, the liver is flushed via the portal vein with 1 L Belzer machine perfusion solution. The perfusion is pressure controlled and set to a mean of 25 mmHg (arterial) and 5 mm Hg (portal). The perfusion fluid is 4 L Belzer machine perfusion solution with additional 3 mmol/L glutathione. The perfusion fluid is 12°C, when the temperature is set at 10°C. The oxygen flow is set at 0.5 mL/min of 100% oxygen on each of the two membrane oxygenators. |
| Care as usual | No intervention | –The donor liver is procured with a segment of 5 cm circular supratruncal aorta left attached to the coeliac trunc. The patients randomized to the control group will receive a liver graft preserved by conventional SCS without any further intervention. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients (≥ 18 years old)
- Signed informed consent
- Willing and able to attend follow-up examinations
- Donor liver graft from a controlled donation after circulatory death (Maastricht category III)
- Donors with a body weight ≥40 kg
Key exclusion criteria (7 listed)
- Simultaneous participation in another clinical trial that might possibly influence this trial
- Mental conditions rendering the subject incapable to understand the nature, scope and consequences of the trial
- Listed for liver transplantation due to fulminant liver failure or retransplantation because of primary non-function
- Recipient positive test for HIV
- Donor positive for HIV antigen, hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody
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 |
|---|---|---|
| Dual hypothermic oxygenated perfusionDual hypothermic oxygenated perfusion using the Liver Assist | Procedure or surgery | Dual hypothermic oxygenated perfusion |
| Liver Assist®The Liver Assist® is the device used to give the intervention dual hypothermic perfusion. | Device | Dual hypothermic oxygenated perfusion |
| Perfusion fluidThe perfusion fluid is Belzer machine perfusion solution University of Wisconsin (Bridge-to-Life, Ltd., Northbrook, IL). | Procedure or surgery | Dual hypothermic oxygenated perfusion |
| GlutathioneGlutathione in a dosage of 3 mmol/ is added to the perfusion fluid according to the intention of use of the perfusion fluid. | Drug | Dual hypothermic oxygenated perfusion |
Primary outcome
The incidence of symptomatic non-anastomotic biliary strictures (NAS)
Time frame: 6 months
NAS is defined as all of the following criteria: * any irregularities or narrowing of the lumen of the intra- or extrahepatic donor bile ducts, but not at the anastomosis * which are diagnosed by cholangiogram (preferably by MRCP) * in the presence of a patent hepatic artery demonstrated by Doppler ultrasonography and if necessary, by computed tomography angiography * and as assessed by the Adjudication Committee * when imaging is indicated by clinical signs (i.e., jaundice, cholangitis) or elevation of cholestatic laboratory parameters in blood samples taken during follow-up
40 secondary outcomes
Asymptomatic NAS
Time frame: 6 months
The severity of NAS
Time frame: 6 months
The location of NAS
Time frame: 6 months
Graft (censored and uncensored for patient death) survival
Time frame: 7 days, 1, 3 , 6, and 12 months after transplantation
Patient survival
Time frame: 7 days, 1, 3 , 6, and 12 months after transplantation
Primary non-function
Time frame: 7 days
Initial poor function
Time frame: 7 days
Biochemical analysis of graft function and ischemia-reperfusion injury
Time frame: Postoperative day 0 - 7 and 1, 3, 6 months
Blood pressure
Time frame: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Heart rate
Time frame: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Vasopressor dosage
Time frame: 5 min before reperfusion, at reperfusion and after 10 and 20 minutes of reperfusion
Length of stay
Time frame: 6 months
Postoperative complications
Time frame: 6 months
Renal function
Time frame: day 7, and 1, 3, 6 months
Flow
Time frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
Pressure
Time frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
Resistance
Time frame: At 0, 15, 30, 45, 60, 75, 90, 105, 120 minutes after start of perfusion
(In selected centers) value of perfusate's pH
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's sodium
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's potassium
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's bicarbonate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's lactate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's alanine transaminase (ALT)
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's aspartate transaminase (AST)
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's alkaline phosphatase (AlkP)
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's gamma glutamyltransferase (γGT)
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's urea
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's total bilirubin
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's thrombomodulin
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's high mobility group box-1 (HMBG) protein
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) value of perfusate's cytochrome C
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-30e in perfusate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-222 in perfusate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA CDmiR-296 in perfusate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA HDmiR-122 in perfusate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
(In selected centers) level of miRNA HDmiR-148a in perfusate
Time frame: At 5 minutes before and at 0.5 hour, 1 hour, 1.5 hours and 2 hours after start of perfusion
Histopathological status liver and bile ducts (in selected centers)
Time frame: Within 0 to 30 minutes before perfusion, at 2 hours of perfusion, and at 1 hour after reperfusion
New onset diabetes after transplantation
Time frame: 90 days
Costs of treatment (in selected centers)
Time frame: within 6 months after transplantation, including transplant operation
Health related quality of life
Time frame: within 6 months before transplantation and 6 months after transplantation
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 12 Jan 2021.
- Derived from this study: PubMed 41082480van Rijn R, Endo C, Kucukerbil EH, Blokzijl H, Blondeel J, Cortes Cerisuelo M, Coenraad MJ, Darwish Murad S, Doukas M, Eker H, de Haas RJ, Huurman VAL, de Meijer VE, Monbaliu D, Schurink IJ, Slangen JJG, Polak WG, de Jonge J, Porte RJ. Long-term Follow-up After Hypothermic Oxygenated Machine Perfusion in DCD Liver Transplantation: Results of a Randomized Controlled Multicenter Trial (DHOPE-DCD). Ann Surg. 2025 Nov 1;282(5):717-724. doi: 10.1097/SLA.0000000000006876. Epub 2025 Aug 5.
- Derived from this study: PubMed 39853733Endo C, van Rijn R, Huurman V, Schurink I, van den Berg A, Murad SD, van Hoek B, de Meijer VE, de Jonge J, van der Hilst CS, Porte RJ. Cost-effectiveness of Dual Hypothermic Oxygenated Machine Perfusion Versus Static Cold Storage in DCD Liver Transplantation. Transplantation. 2025 Feb 1;109(2):e101-e108. doi: 10.1097/TP.0000000000005232. Epub 2024 Oct 8.
- Derived from this study: PubMed 33626248van Rijn R, Schurink IJ, de Vries Y, van den Berg AP, Cortes Cerisuelo M, Darwish Murad S, Erdmann JI, Gilbo N, de Haas RJ, Heaton N, van Hoek B, Huurman VAL, Jochmans I, van Leeuwen OB, de Meijer VE, Monbaliu D, Polak WG, Slangen JJG, Troisi RI, Vanlander A, de Jonge J, Porte RJ; DHOPE-DCD Trial Investigators. Hypothermic Machine Perfusion in Liver Transplantation - A Randomized Trial. N Engl J Med. 2021 Apr 15;384(15):1391-1401. doi: 10.1056/NEJMoa2031532. Epub 2021 Feb 24.
- Derived from this study: PubMed 31420387de Vries Y, Berendsen TA, Fujiyoshi M, van den Berg AP, Blokzijl H, de Boer MT, van der Heide F, de Kleine RHJ, van Leeuwen OB, Matton APM, Werner MJM, Lisman T, de Meijer VE, Porte R. Transplantation of high-risk donor livers after resuscitation and viability assessment using a combined protocol of oxygenated hypothermic, rewarming and normothermic machine perfusion: study protocol for a prospective, single-arm study (DHOPE-COR-NMP trial). BMJ Open. 2019 Aug 15;9(8):e028596. doi: 10.1136/bmjopen-2018-028596.
- Derived from this study: PubMed 30866837van Rijn R, van den Berg AP, Erdmann JI, Heaton N, van Hoek B, de Jonge J, Leuvenink HGD, Mahesh SVK, Mertens S, Monbaliu D, Muiesan P, Perera MTPR, Polak WG, Rogiers X, Troisi RI, de Vries Y, Porte RJ. Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial. BMC Gastroenterol. 2019 Mar 12;19(1):40. doi: 10.1186/s12876-019-0956-6.
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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.
Robert J. Porte, MD PhD Prof principal investigator
University Medical Center Groningen
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Dual hypothermic oxygenated perfusion, Liver Assist® and Perfusion fluid in people with Liver Failure and End Stage Liver Disease, run by Robert J. Porte at 6 sites in 3 countries.
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 5 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 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands, Belgium, United Kingdom. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The incidence of symptomatic non-anastomotic biliary strictures (NAS) (time frame: 6 months). 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 NCT02584283, which also lists 5 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 12 Jan 2021.