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Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation

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ClinicalTrials.gov Identifier: NCT02515708
Recruitment Status : Recruiting
First Posted : August 5, 2015
Last Update Posted : August 31, 2018
Sponsor:
Information provided by (Responsible Party):
Cristiano Quintini, The Cleveland Clinic

Brief Summary:
Normothermic machine perfusion (NMP) preservation is a promising method to decrease the complication of marginal donor livers compared to cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation. This will be a single center prospective cohort pilot study. Thirty-two livers with acceptable quality for transplantation will be preserved with NMP in 2-18 hours and transplanted. The follow-up period will be 6 months post-transplantation. The outcome will be compared to 100 historical patients transplanted in our program in the past 5 years (liver preserved using CS) with matched characteristics on age, Model for End-Stage Liver Disease (MELD) score, preservation time, etc.

Condition or disease Intervention/treatment Phase
Liver Transplantation Device: Normothermic Liver perfusion Device Not Applicable

Detailed Description:

The shortage of donor organs leads to the use of marginal donors including donors after cardiac death. Normothermic machine perfusion (NMP) preservation is a promising method to decrease their high risk of complication compared to the standard cold storage (CS). The aim of this project is to assess safety and feasibility of NMP in human liver transplantation.

This will be a single center prospective cohort pilot study. Thirty-two livers that have acceptable quality for transplantation will be preserved with NMP in 2-18 hours after cross clamp and cold flush. The liver grafts at NMP will be at physiological temperature and have oxygen and nutrient supply with continuous perfusion. The transplantation and post-transplant care will follow the standard of care. The follow-up period is 12 months after transplantation. The primary end point will be the rate of post-transplant Early Allograft Dysfunction (EAD), while the secondary end points will be: primary non function (PNF) rate, 1 and 6 months patient and graft survival, peak liver function tests in the first 7 days after transplantation, intraoperative hepatic arterial and portal flow measurement, rate and magnitude of post-reperfusion syndrome, surgical outcomes (operative time, transfusion requirement etc.), rate of post-transplant kidney failure, assessment of histological ischemia reperfusion (liver and bile duct), rate of vascular complications, rate of biliary complications, hospital and ICU length of stay, rejection rate, infection rate, the ability to predict function based on "on-pump" viability markers, and the incidence of adverse effect (AE).

The outcome will be compared to a control group of 100 historical patients (matched with a 1:4 ratio) transplanted in our program in the past 10 years (liver preserved using CS). Control subjects will be matched using donor and recipient age, Model for End-Stage Liver Disease (MELD) score, cold ischemia time, donor risk index and presence of steatosis.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Pilot Study to Assess Safety and Feasibility of Normothermic Machine Preservation In Human Liver Transplantation
Actual Study Start Date : May 16, 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Normothermic Liver perfusion
This group has the liver grafts preserved using the Normothermic Liver perfusion Device.
Device: Normothermic Liver perfusion Device
The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.

Normothermic Machine Perfusion (single pump)
This group has the liver grafts preserved using a single-pump variant of the Normothermic Liver perfusion Device.
Device: Normothermic Liver perfusion Device
The liver grafts will be preserved at physiological temperature and have continuous perfusion with oxygen and nutrient supply in the ex vivo organ preservation phase.




Primary Outcome Measures :
  1. the rate of Early Allograft Dysfunction post-transplantation in Normothermically Machine Perfused (NMP) livers [ Time Frame: 7 days post-transplantation ]
    The presence of at least one of the following at post-transplant 7 days: serum bilirubin >= 10 mg/dL, international normalized ratio (INF) >= 1.6; and/or aspartate aminotransferase (AST) > 2000 U/L at any time in the first 7 post-transplant days (POD)


Secondary Outcome Measures :
  1. primary non-function rate [ Time Frame: in the first 10 days post-transplantation ]
  2. graft survival [ Time Frame: 6 months post-transplantation ]
    The allograft will be considered lost if a patient has a liver re-transplant or in the event of patient death.

  3. peak liver function tests in the first 7 days post-transplantation [ Time Frame: in the first 7 days post-transplantation ]
  4. intraoperative flow measurement [ Time Frame: intraoperative ]
    Flows will be measured with a transit time flowmeter (VeriQ system, MediStim A/S, Oslo, Norway) after graft reperfusion. The following parameters will be recorded as per our standard practice during liver transplantation: portal venous flow, hepatic artery flow, and hepatic artery flow after temporary portal vein occlusion.

  5. post reperfusion syndrome (composite) [ Time Frame: in the first 7 days post-transplantation ]
    rate and magnitude

  6. surgical outcomes (composite) [ Time Frame: intraoperative ]
    operative time, transfusion requirement

  7. rate of post-transplant kidney failure [ Time Frame: in the 1, 3, 6 ,9 months post-transplantation ]
  8. histology of liver parenchyma [ Time Frame: On the day of transplantation ]
  9. vascular complications rate [ Time Frame: in the first day post-transplantation ]
  10. biliary complications rate [ Time Frame: 6 months post-transplantation ]
  11. hospital and ICU length of stay (composite) [ Time Frame: 6 months post-transplantation ]
  12. rejection rate [ Time Frame: 6 months post-transplantation ]
  13. opportunistic viral infection rate [ Time Frame: 6 months post-transplantation ]
  14. patient survival [ Time Frame: 6 months post-transplantation ]
  15. histology of bile duct [ Time Frame: On the day of transplantation ]


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing primary liver transplantation
  • Age 18-75 years at the time of transplantation
  • Willingness and ability to comply with the study procedures
  • Signed Informed Consent Form
  • For patients with hepatocellular carcinoma as indication for Orthoptic Liver Transplantation (OLT), tumor must be within Milan Criteria or down-staged to Milan Criteria.

Exclusion Criteria:

Recipient Exclusion Criteria:

  • History of prior solid organ transplantation
  • Patient on a respiratory and/or cardiocirculatory support at the time of transplant
  • MELD score >35
  • HIV positive patient
  • Patient with current severe systemic infection
  • Multiorgan transplant

Donor Exclusion Criteria:

  • Donor age <14 or >70 years
  • Liver steatosis (on visual estimate or on liver biopsy) > 30%
  • Donors with Grade 2-3 traumatic liver laceration
  • Partial grafts (living donors and split liver donors)
  • Liver in which the investigator is unwilling or unable (for logistical reasons) to perform normothermic machine perfusion (NMP) preservation
  • Inability to NMP perfuse the liver within 4 hours after cross clamp

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02515708


Contacts
Contact: Cristiano Quintini, MD 216 445-3388 quintic@ccf.org
Contact: Susan Thomas, RN 216-444-5930 thomass4@ccf.org

Locations
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Susan Thomas, RN    216-444-5930    thomass4@ccf.org   
Contact: Cristiano Quintini, MD    216 445-3388    quintic@ccf.org   
Sponsors and Collaborators
Cristiano Quintini
Investigators
Principal Investigator: Cristiano Quintini, MD The Cleveland Clinic

Responsible Party: Cristiano Quintini, Sponsor-Investigator, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02515708     History of Changes
Other Study ID Numbers: 15-549
First Posted: August 5, 2015    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Liver Extracts
Hematinics