Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation (HOPExt) (HOPExt)
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|ClinicalTrials.gov Identifier: NCT03929523|
Recruitment Status : Recruiting
First Posted : April 29, 2019
Last Update Posted : February 5, 2020
Given the scarce donor supply, an increasing number of so-called marginal or extended criteria donor (ECD) organs have been used for liver transplantation. These ECD liver grafts are, however, known to be associated with a higher rate of early allograft dysfunction (EAD) and primary non-function because of a greater vulnerability to ischemia-reperfusion injury. The end-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) technique may improve outcomes of liver transplantation with ECD grafts by decreasing reperfusion injury.
The study aim is to assess the efficacy of HOPE used before transplantation of ECD liver grafts from brain-dead donors in reducing postoperative EAD within the first 7 postoperative days (POD) compared to simple cold static storage.
The study is comparative open-label, multicenter, national, prospective, randomized, in two parallel groups, using the gold standard procedure as control.
|Condition or disease||Intervention/treatment||Phase|
|Liver Transplantation||Device: End-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE) Device: classic static cold storage||Not Applicable|
This multicentric randomized controlled trial concerns adult patients undergoing whole liver transplantation in any of the 8 participating centers in France, who will receive an ECD liver graft from a brain-dead donor.
After providing written informed consent prior to the performance of any study specific procedure, the recruited patients will be randomized either in the experimental group (HOPE group) or in the control group.
In the HOPE group, ECD liver grafts will undergo a hypothermic oxygenated perfusion (HOPE) via the portal vein for a period of 1 to 4 hours (minimum 1 hour) after the "back-table" phase (graft preparation), in parallel with the recipient hepatectomy, using the CE-certified Liver Assist® perfusion pump/device (Organ Assist®, the Netherlands) with Machine Perfusion Solution (Belzer-MPS, CE-certified).
The control group will consist of a classic static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until liver transplantation, which is the gold standard procedure in liver transplantation.
The primary endpoint will be early allograft dysfunction (EAD) according to Olthoff's criteria, which will be compared with the Model of Early Allograft Function score (MEAF score) and the Liver Graft Assessment Following Transplantation risk factor (L-GrAFT).
According to the primary endpoint, a sample size of 133 patients per randomized group (266 in total) is needed. The duration of the inclusion period is expected to be 24 months with a 1-year follow-up for each patient.
The potential impacts of the study are expected on 3 levels: (1) for the patient, decreased postoperative morbidity and mortality of liver transplantation with ECD donors; (2) for the French liver transplantation community, familiarization with liver machine perfusion, and (3) economically, decreased costs of liver transplantation (health economic analysis included in the study).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||266 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||End-ischemic Hypothermic Oxygenated Perfusion for Extended Criteria Donors in Liver Transplantation - A Multicenter, Randomized Controlled Trial|
|Actual Study Start Date :||September 10, 2019|
|Estimated Primary Completion Date :||September 2022|
|Estimated Study Completion Date :||September 2022|
Experimental: HOPE group
hypothermic oxygenated perfusion
Device: End-ischemic Hypothermic Oxygenated Machine Perfusion (HOPE)
In the experimental group, ECD liver grafts will first undergo a classical static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until transport to the transplantation center. They will then undergo a hypothermic oxygenated perfusion (HOPE) via the portal vein for a period of 1 to 4 hours (minimum 1 hour) after the "back-table" phase (graft preparation), in parallel with the recipient hepatectomy, using the CE-certified Liver Assist® perfusion pump/device (Organ Assist®, the Netherlands) with Machine Perfusion Solution (Belzer-MPS, CE-certified).
Active Comparator: Control group
classic static cold storage
Device: classic static cold storage
The control group will consist of a classic static cold (4°C) storage with Institute George Lopez (IGL-1)® solution from graft harvesting until liver transplantation, which is the gold standard procedure in liver transplantation
- Early allograft dysfunction (EAD) according to Olthoff criteria. [ Time Frame: During the first postoperative week ]
EAD is defined by the presence of at least one of the following criteria:
- Bilirubin level > 10 mg/dL (i.e. 171 µmol/L) on POD 7
- International Normalized Ratio (INR) > 1.6 on POD 7
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > 2000 IU/L within the first 7 PODs Additionally EAD will be also assessed by the MEAF score and the L-GrAFT risk factor.
- Model of Early Allograft Function score (MEAF score). [ Time Frame: During the first 3 postoperative days. ]The MEAF score includes bilirubin, ALT max and INR max at postperative day 3. Range 0 (better outcome) to 10 (worse outcome)
- Liver Graft Assessment Following Transplantation risk factor (L-GrAFT) [ Time Frame: During the first 10 postoperative days. ]L-GrAFT includes aspartate aminotransferase (AST), INR, total bilirubin and platelets every day until postoperative day 10. Range -6 (better outcome) to +6 (worse outcome)
- Untargeted liver graft metabolic profiling [ Time Frame: Day of liver transplantation (Day 0) ]Untargeted liver graft metabolic profiling (by High-Resolution Nuclear Magnetic Resonance - 1H HR-Nuclear Magnetic Resonance (NMR) Spectrometer) on liver graft biopsies on the back-table before and after liver machine perfusion.
- Occurrence of post-reperfusion syndrome [ Time Frame: Day of liver transplantation (Day 0) ]Defined as a 50% decrease in median arterial pressure during the 5 minutes following the graft revascularization
- 90-day morbidity and mortality [ Time Frame: During the first 90 days after surgery. ]Severe postoperative complications (Dindo-Clavien ≥3) / death
- Length of intermediate care unit stay (days) [ Time Frame: From randomization until intermediate care unit discharge, estimated up to 7 days ]Duration of intermediate care unit stay
- Length of hospital stay (days) [ Time Frame: From randomization until hospital discharge, estimated up to 21 days ]Duration of hospital stay
- Liver contrast-enhanced MRI including a Magnetic Resonance CholangioPancreatography (MRCP) [ Time Frame: Within 1 year after liver transplantation ]Assessment of intra- and extrahepatic biliary complications
- 3-month and one-year patient and graft survivals [ Time Frame: within one year after liver transplantation ]Actuarial graft and patient's survival rates
- Hospital costs (Euros) of liver transplantation [ Time Frame: At one year after liver transplantation ]Hospital costs of liver transplantation
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929523
|Contact: Mickael LESURTEL||+33 4 72 07 11 firstname.lastname@example.org|
|Contact: Mahé RAFFIN||+33 4 26 73 27 email@example.com|
|Department of HPB surgery and liver transplantation Beaujon University Hospital||Not yet recruiting|
|Clichy, France, 92210|
|Contact: Olivier SOUBRANE +33 1 40 87 50 00 firstname.lastname@example.org|
|CHU Grenoble Alpes - Department of HPB surgery and liver transplantation||Not yet recruiting|
|Grenoble, France, 38000|
|Contact: Mircea CHIRICA +33 4 76 76 75 75 email@example.com|
|Principal Investigator: Mircea CHIRICA|
|Sub-Investigator: Agnès BONADONA|
|Department of HPB surgery and liver transplantation Claude Huriez University Hospital||Recruiting|
|Lille, France, 59037|
|Contact: Emmanuel BOLESLAWSKI +33 3 20 44 42 60 firstname.lastname@example.org|
|Hospices Civils de Lyon||Recruiting|
|Lyon, France, 69004|
|Contact: Mickaël LESURTEL +33 4 72 07 11 00 email@example.com|
|Contact: Mahé RAFFIN +33 4 26 73 27 38 firstname.lastname@example.org|
|APHP - Pitié Salpétrière||Not yet recruiting|
|Paris, France, 75013|
|Contact: Olivier SCATTON email@example.com|
|Principal Investigator: Olivier SCATTON|
|Department of HPB surgery and liver transplantation Pontchaillou University Hospital||Recruiting|
|Rennes, France, 35033|
|Contact: Michel RAYAR firstname.lastname@example.org|
|Hôpital Hautepierre - Department of HPB surgery and liver transplantation||Recruiting|
|Strasbourg, France, 67200|
|Contact: Philippe BACHELLIER email@example.com|
|Department of HPB surgery and liver transplantation Paul Brousse University Hospital||Recruiting|
|Villejuif, France, 94804|
|Contact: René ADAM +33 1 45 59 30 49 firstname.lastname@example.org|
|Principal Investigator:||Mickael LESURTEL||Hospices Civils de Lyon|