Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

HOPE for Human Extended Criteria and Donation After Brain Death Donor (ECD-DBD) Liver Allografts (HOPE-ECD-DBD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03124641
Recruitment Status : Completed
First Posted : April 24, 2017
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Georg Lurje, M.D., University Hospital, Aachen

Tracking Information
First Submitted Date  ICMJE March 20, 2017
First Posted Date  ICMJE April 24, 2017
Last Update Posted Date January 28, 2021
Actual Study Start Date  ICMJE January 17, 2017
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2017)
Early graft injury [ Time Frame: During the first week postoperatively (absolute and relative delta) ]
Peak serum alanine aminotransferase-ALT
Original Primary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
Early graft function [ Time Frame: During the first week postoperatively ]
Peak serum alanine aminotransferase-ALT
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 9, 2017)
  • Postoperative complications [ Time Frame: Subjects will be followed for one year postoperatively ]
    Clavien-Dindo complication score
  • Cumulative postoperative complications [ Time Frame: Subjects will be followed for one year postoperatively ]
    Comprehensive complication index (CCI)
  • Early allograft dysfunction (EAD) [ Time Frame: During the first week postoperatively ]
    Olthoff criteria (bilirubin 10mg/dL on day 7, international normalized ratio 1.6 on day 7, and alanine or aspartate aminotransferases >2000 IU/L)
  • Duration of intensive care stay [ Time Frame: Subjects will be followed for one year postoperatively ]
    Duration of ICU stay
  • Duration of hospital stay [ Time Frame: Subjects will be followed for one year postoperatively ]
    Duration of hospitalisation
  • One-year recipient- and graft survival [ Time Frame: Subjects will be followed for one year postoperatively ]
    One year patient and graft survival
  • Ischemia-reperfusion injury and inflammatory responses [ Time Frame: Before preservation (HOPE or CCS), after liver implantation (0-3 hrs) ]
    Liver samples taken upon arrival of the organ (before HOPE or corresponding cold-storage), and at the end of the implantation procedure before closure of the abdomen
  • (in selected centers) Biliary epithelial cell injury [ Time Frame: Postoperative days 1, 2, and 3 ]
    Bile samples collected from T-Drain
Original Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
  • Postoperative complications [ Time Frame: Subjects will be followed for one year postoperatively ]
    Clavien-Dindo complication score
  • Cummulative postoperative complications [ Time Frame: Subjects will be followed for one year postoperatively ]
    Comprehensive complication index (CCI)
  • Duration of intensive care stay [ Time Frame: Subjects will be followed for one year postoperatively ]
    Duration of ICU stay
  • Duration of hospital stay [ Time Frame: Subjects will be followed for one year postoperatively ]
    Duration of hospitalisation
  • One-year recipient- and graft survival [ Time Frame: Subjects will be followed for one year postoperatively ]
    One year patient and graft survival
  • Inflammatory response and reperfusion injury [ Time Frame: Before preservation (HOPE or CCS), during reperfusion after liver implantation (0-3 hr) ]
    Liver samples taken after procurement, before HOPE, after HOPE or after cold storage, respectively, and at the end of implantation before closure of the abdomen to evaluate the amount of ischemia reperfusion (I/R) injury.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HOPE for Human Extended Criteria and Donation After Brain Death Donor (ECD-DBD) Liver Allografts
Official Title  ICMJE Hypothermic Oxygenated Machine Perfusion (HOPE) for Liver Transplantation of Human Liver Allografts From Extended Criteria Donors (ECD) in Donation After Brain Death (DBD); a Multicenter Randomized Controlled Trial (HOPE ECD-DBD)
Brief Summary

The purpose of this study is to test the effects of hypothermic oxygenated machine perfusion (HOPE) in a phase-II prospective multicenter randomized clinical trial (RCT) on extended criteria donor allografts (ECD) in donation after brain death (DBD) orthotropic liver-transplantation (OLT) (HOPE-ECD-DBD). Human whole organ liver grafts will be submitted to 1-2 hours of HOPE via the portal vein directly before implantation and going to be compared to a control-group of patients transplanted after conventional cold storage (CCS). Primary (early graft injury) and secondary (e.g. postoperative complications, hospital stay, survival) objectives are going to be analysed in a 12 month follow up. Ischemia-reperfusion (I/R) injury and inflammation will be assessed using liver tissue, serum and bile samples as well as machine perfusion perfusate.

To improve the availability of donor allografts and reduce waiting list mortality, graft acceptance criteria were extended increasingly over the decades. The use of extended criteria donor (ECD) allografts is associated with higher incidences of primary graft non-function (PNF) and/or delayed graft function (DGF). As such, several strategies have been developed aiming at "reconditioning" poor quality ECD grafts. HOPE has been tested intensively in pre-clinical animal experiments. Although, its known that HOPE can exert its reconditioning effect via cellular and mitochondrial pathways in the endothelial and parenchymal cells, there is still scarce evidence available on the exact subcellular mechanism of HOPE induced organ protection in the clinical scenario of liver transplantation. In donation after cardiac death (DCD) OLT, the positive effects of HOPE have been shown to reduce the incidence of biliary complications, mitochondrial damage and improve the overall cellular energy-status.

In the HOPE setting, organ perfusion is performed in the transplant center shortly before the actual implantation with oxygenated perfusate using an extra corporal organ perfusion system. The first clinical study with this promising technique was recently reported in a Swiss cohort of patients who received DCD allografts. In organ donation after brain death (DBD), the only legally accepted approach for organ donation in most countries, HOPE and its effect on early graft injury and postoperative complications remains to be elucidated.

Detailed Description

The present RCT comprises two groups, a perfusion (group 1; HOPE) and a control conventional cold storage (group 2; CCS) group. Patients with proven written informed consent on waiting list for orthotopic liver transplantation will be recruited. Randomization is performed with an online randomizing tool for clinical trials (www.randomizer.at) at the time of allograft arrival at the transplant center and acceptance of the organ for transplantation. Stratified randomization model will be used to ensure balance of prognostic variables between the treatment groups.

In case of randomisation to group 1, HOPE will be applied to the allograft in the operation room, directly after the back table preparation. The application of HOPE to the liver allograft will not delay the implantation due to the fact that it is performed parallel to the recipient hepatectomy.

Commercially available and machine-perfusion approved Belzer MPS® UW solution (Belzer Organ Preservation Solutions, Bridge for Life) will be used as perfusate for machine perfusion.

Patients will be followed for one year after OLT.

Interim analysis: After n=12 per randomized group is reached, data will be analyzed by an independent Data Monitoring Committee. The RCT will be stopped if one of the following criteria is reached:

Significantly higher serum ALT levels (p<0.001 using Student's t-test) in the HOPE group compared to the CCS group (Efficacy).

The proportion of Grade ≥ III complications is significantly higher (p<0.05, Fischer's exact test) in the HOPE group when compared to the CCS group (Safety).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized controlled trial
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatocellular Injury
  • Liver Transplant
Intervention  ICMJE
  • Device: Hypothermic oxygenated perfusion (HOPE)
    HOPE for 1 hour via the portal vein in a recirculating and pressure controlled system (2-3 mm Hg), 0.1 ml/g liver/min, perfusion volume 3-4 L, Belzer (UW) machine perfusion solution, perfusate temperature 10 °C, perfusate oxygenation pO2 of 60-80 kPa
    Other Name: Hypothermic machine perfusion (HMP)
  • Procedure: Conventional cold storage (CCS)
    Conventional static cold storage (CCS) on temperature 4-6 °C from organ procurement
    Other Name: CCS
Study Arms  ICMJE
  • Experimental: Hypothermic oxygenated perfusion (HOPE)
    Application of Hypothermic machine perfusion (HOPE) for 1-2 hours
    Intervention: Device: Hypothermic oxygenated perfusion (HOPE)
  • Active Comparator: Conventional cold storage (CCS)
    Conventional cold storage
    Intervention: Procedure: Conventional cold storage (CCS)
Publications * Czigany Z, Schöning W, Ulmer TF, Bednarsch J, Amygdalos I, Cramer T, Rogiers X, Popescu I, Botea F, Froněk J, Kroy D, Koch A, Tacke F, Trautwein C, Tolba RH, Hein M, Koek GH, Dejong CHC, Neumann UP, Lurje G. Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD). BMJ Open. 2017 Oct 10;7(10):e017558. doi: 10.1136/bmjopen-2017-017558.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 18, 2017)
46
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 30, 2020
Actual Primary Completion Date September 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

-Patients with signed informed consent, suffering from end stage-liver disease and/or malignant liver tumors listed for liver transplantation and receiving ECD organs.

ECD Criteria are defined as:

  • Donors 65 years of age and older
  • Intensive therapy of the donor was required before donation for at least 7 days, --Obesity of the donor with a Body Mass Index > 30
  • Fatty liver (with histology) > 40 %
  • Serum-Sodium > 165 mmol/l
  • Serum AST or ALT > 3 x normal, Serum-Bilirubin > 2 mg/dl)

Exclusion Criteria:

  • Recipients of split of living donor liver transplants
  • Previous liver transplantation
  • Combined transplantations (liver-kidney, liver-lung, etc.)
  • Participation in other liver related trials
  • The subject received an investigational drug within 30 days prior to inclusion
  • The subject is unwilling or unable to follow the procedures outlined in the protocol
  • The subject is mentally or legally incapacitated
  • Patient is not able to understand the procedures due to language barriers
  • Family members of the investigators or employees of the participating department
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Germany
Removed Location Countries Belgium,   Romania
 
Administrative Information
NCT Number  ICMJE NCT03124641
Other Study ID Numbers  ICMJE EK 049/17
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Georg Lurje, M.D., University Hospital, Aachen
Study Sponsor  ICMJE University Hospital, Aachen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Georg Lurje, M.D. RWTH Aachen University I Charité-Universitätsmedizin Berlin
PRS Account University Hospital, Aachen
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP