CClinicalTrials.gg
Sign In
CompletedNCT02775162Updated Jul 29, 2022Results posted

WP01 - Normothermic Liver Preservation

An interventional study of Normothermic Machine Perfusion (NMP) and Standard of Care (Ice) in Liver Transplantation, sponsored by OrganOx Ltd.. Completed at 15 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-07-29.

Sponsored by OrganOx Ltd. · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
267
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

A multicenter randomized controlled trial to compare the efficacy of ex-vivo normothermic machine profusion with static cold storage in human liver transplantation.

02

Conditions studied

  • Liver Transplantation
03

In context

Lead sponsor

OrganOx Ltd. is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Subject is 18 years of age or greater
  • Subject is registered as an active recipient on the United Network for Organ Sharing (UNOS) waiting list for liver transplantation
  • Subject, or legally authorized representative, is able and willing to give informed consent and HIPAA authorization
  • Subject is able and willing to comply with all study requirements

Exclusion criteria

Exclusion Criteria:

  • Subject requiring all of the following at the time of transplantation: oxygen therapy, inotropic support, renal replacement therapy
  • Subject has acute/fulminant liver failure
  • Subject undergoing simultaneous transplantation of more than one organ
  • Subject is pregnant or nursing
  • Concurrent enrollment in another clinical trial. Subjects enrolled in clinical trials or registries where only measurements and/or samples are taken (NO TEST DEVICE or TEST DRUG USED) are allowed to participate.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
267 participants (actual)

Study arms

  • Experimental
    Normothermic Machine Perfusion (NMP)

    Following the routine retrieval procedure of the liver, it will be placed on the OrganOx metra for Normothermic Machine Perfusion (NMP) for transport per the Investigational Plan and the Instructions For Use.

    Device: Normothermic Machine Perfusion (NMP)

  • Other
    Standard of Care (Ice)

    Following the routine retrieval procedure of the liver, it will be placed in ice-cold perfusion solution within an ice box for transport as dictated by logistics and local policy.

    Other: Standard of Care (Ice)

Interventions

  • DeviceNormothermic Machine Perfusion (NMP)

    Also known as: OrganOx metra® device

  • OtherStandard of Care (Ice)
06

What researchers measure

Primary outcomes

  1. Percentage of Participants With Early Allograft Dysfunction (EAD)

    EAD is a binary outcome defined by the presence of one of the following 3 outcomes: * Serum bilirubin ≥ 10 mg/dL at day 7 post-transplant * International normalized ratio (INR) ≥ 1.6 at day 7 post-transplant * Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) \> 2000 IU/L within the first 7 days post-transplant

    Time frame: 7 Days

Secondary outcomes

  1. Number of Participants With Primary Non-Function

    Primary Non-Function is defined in this study as irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation.

    Time frame: 10 Days

  2. Number of Participants With Graft Survival

    Time frame: 6 Months

  3. Number of Participants With Subject Survival

    Time frame: 6 Months

  4. Number of Participants With Post-Reperfusion Syndrome

    Post-Reperfusion Syndrome is defined in this study as a decrease in mean arterial pressure (MAP) of more than 30% from the baseline value for more than one minute during the first five minutes after reperfusion.

    Time frame: 1 Day

  5. Measure Biochemical Liver Function Via Bilirubin

    Time frame: 6 Months

  6. Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)

    Time frame: 6 Months

  7. Measure Biochemical Liver Function Via Alanine Aminotransferase (ALT)

    Time frame: 6 Months

  8. Measure Biochemical Liver Function Via Aspartate Transaminase (AST)

    Time frame: 6 Months

  9. Measure Biochemical Liver Function Via Alkaline Phosphatase (ALP)

    Time frame: 6 Months

  10. Measure Biochemical Liver Function Via International Normalized Ratio (INR)

    The international normalized ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. It is calculated using the following formula: INR = (PT \[test\] / PT \[control\])\^ISI INR = international normalized ratio PT \[test\] = tested prothrombin time PT \[control\] = control prothrombin time ISI = international sensitivity index

    Time frame: 6 Months

  11. Measure Biochemical Liver Function Via Lactate

    Time frame: Days 1-7

  12. Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies

    Overall Degree of Ischemia Reperfusion Injury (IRI) was categorized as: * None/Minimal: None or Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with rare hepatocellular necrosis * Mild: Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with ≥ 1 cluster of necrotic hepatocytes * Moderate/Severe: Clusters of hepatocellular necrosis in \> 50% of lobules or 60% of parenchyma or panlobular necrosis in \> 1 lobule

    Time frame: 1 Day

  13. Number of Participants With Biliary Investigations and Biliary Interventions

    Time frame: 6 Months

  14. Number of Livers Randomized But Not Transplanted

    Time frame: 1 Day

  15. Number of Livers That Did Not Experience a Safety Event

    Number of livers that did not experience at least one of the following safety events: * Early Allograft Dysfunction (EAD) * Discard of a Retrieved Liver * Primary Non-Function (PNF)

    Time frame: 10 Days

  16. Assessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay

    Time frame: 6 Months

  17. Compare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire

    The EQ-5D-5L Questionnaire is the standard layout for recording an adult person's current self-reported health state. It consists of a standard format for respondents to record their health state according to the EQ-5D-5L descriptive system and the EQ Visual Analog Scale (VAS). EQ-5D-5L index scores range from 0 to 1.0 on a scale where 0 = death and 1.0 = perfect health. EQ-5D-5L is the name of the instrument and is not an acronym.

    Time frame: 6 Months

07

Results

Posted Jul 22, 2022

Participant flow

Participant flow — Overall Study
MilestoneNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Started136131
Completed122121
Not completed1410

Outcome measures

PrimaryPercentage of Participants With Early Allograft Dysfunction (EAD)

EAD is a binary outcome defined by the presence of one of the following 3 outcomes: * Serum bilirubin ≥ 10 mg/dL at day 7 post-transplant * International normalized ratio (INR) ≥ 1.6 at day 7 post-transplant * Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) \> 2000 IU/L within the first 7 days post-transplant

Time frame:
7 Days
Reported as:
Number · percentage of participants
Percentage of Participants With Early Allograft Dysfunction (EAD)
percentage of participantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Percentage of Participants With Early Allograft Dysfunction (EAD)20.6 (14.5 to 28.5)23.7 (17.1 to 31.9)
SecondaryNumber of Participants With Primary Non-Function

Primary Non-Function is defined in this study as irreversible graft dysfunction requiring emergency liver replacement during the first 10 days after liver transplantation.

Time frame:
10 Days
Reported as:
Count of participants · Participants
Number of Participants With Primary Non-Function
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Participants With Primary Non-Function12
SecondaryNumber of Participants With Graft Survival
Time frame:
6 Months
Reported as:
Count of participants · Participants
Number of Participants With Graft Survival
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Participants With Graft Survival124122
SecondaryNumber of Participants With Subject Survival
Time frame:
6 Months
Reported as:
Count of participants · Participants
Number of Participants With Subject Survival
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Participants With Subject Survival121123
SecondaryNumber of Participants With Post-Reperfusion Syndrome

Post-Reperfusion Syndrome is defined in this study as a decrease in mean arterial pressure (MAP) of more than 30% from the baseline value for more than one minute during the first five minutes after reperfusion.

Time frame:
1 Day
Reported as:
Count of participants · Participants
Number of Participants With Post-Reperfusion Syndrome
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Participants With Post-Reperfusion Syndrome819
SecondaryMeasure Biochemical Liver Function Via Bilirubin
Time frame:
6 Months
Reported as:
Median · mg/dL
Measure Biochemical Liver Function Via Bilirubin
mg/dLNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Bilirubin0.6 (0.4 to 0.8)0.5 (0.4 to 0.7)
SecondaryMeasure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)
Time frame:
6 Months
Reported as:
Median · IU/L
Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)
IU/LNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Gamma-Glutamyl Transferase (GGT)38.5 (21.5 to 78.0)34.0 (20.0 to 72.0)
SecondaryMeasure Biochemical Liver Function Via Alanine Aminotransferase (ALT)
Time frame:
6 Months
Reported as:
Median · IU/L
Measure Biochemical Liver Function Via Alanine Aminotransferase (ALT)
IU/LNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Alanine Aminotransferase (ALT)23.0 (16.0 to 39.0)21.0 (16.0 to 32.0)
SecondaryMeasure Biochemical Liver Function Via Aspartate Transaminase (AST)
Time frame:
6 Months
Reported as:
Median · IU/L
Measure Biochemical Liver Function Via Aspartate Transaminase (AST)
IU/LNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Aspartate Transaminase (AST)24.0 (18.0 to 30.0)20.0 (16.0 to 26.0)
SecondaryMeasure Biochemical Liver Function Via Alkaline Phosphatase (ALP)
Time frame:
6 Months
Reported as:
Median · IU/L
Measure Biochemical Liver Function Via Alkaline Phosphatase (ALP)
IU/LNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Alkaline Phosphatase (ALP)94.0 (72.0 to 137.0)92.0 (68.0 to 115.0)
SecondaryMeasure Biochemical Liver Function Via International Normalized Ratio (INR)

The international normalized ratio (INR) is a laboratory measurement of how long it takes blood to form a clot. It is calculated using the following formula: INR = (PT \[test\] / PT \[control\])\^ISI INR = international normalized ratio PT \[test\] = tested prothrombin time PT \[control\] = control prothrombin time ISI = international sensitivity index

Time frame:
6 Months
Reported as:
Median · No Units
Measure Biochemical Liver Function Via International Normalized Ratio (INR)
No UnitsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via International Normalized Ratio (INR)1.0 (1.0 to 1.1)1.0 (1.0 to 1.1)
SecondaryMeasure Biochemical Liver Function Via Lactate
Time frame:
Days 1-7
Reported as:
Median · mmol/L
Measure Biochemical Liver Function Via Lactate
mmol/LNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Measure Biochemical Liver Function Via Lactate1.4 (1.0 to 2.1)1.5 (1.0 to 1.9)
SecondaryNumber of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies

Overall Degree of Ischemia Reperfusion Injury (IRI) was categorized as: * None/Minimal: None or Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with rare hepatocellular necrosis * Mild: Polymorphonuclear Leukocytes (PMNs) in sinusoidal zone 3 with ≥ 1 cluster of necrotic hepatocytes * Moderate/Severe: Clusters of hepatocellular necrosis in \> 50% of lobules or 60% of parenchyma or panlobular necrosis in \> 1 lobule

Time frame:
1 Day
Reported as:
Count of participants · Participants
Number of Participants With Evidence of Ischemia-Reperfusion Injury Via Comparison of Pre-Reperfusion Biopsies to Post-Reperfusion Biopsies
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Pre-Reperfusion — None/Minimal123117
Pre-Reperfusion — Mild105
Pre-Reperfusion — Moderate/Severe00
Post-Reperfusion — None/Minimal10093
Post-Reperfusion — Mild2924
Post-Reperfusion — Moderate/Severe45
SecondaryNumber of Participants With Biliary Investigations and Biliary Interventions
Time frame:
6 Months
Reported as:
Count of participants · Participants
Number of Participants With Biliary Investigations and Biliary Interventions
ParticipantsNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Biliary Investigations1416
Biliary Interventions1211
SecondaryNumber of Livers Randomized But Not Transplanted
Time frame:
1 Day
Reported as:
Count of units · Livers
Number of Livers Randomized But Not Transplanted
LiversNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Livers Randomized But Not Transplanted5661
SecondaryNumber of Livers That Did Not Experience a Safety Event

Number of livers that did not experience at least one of the following safety events: * Early Allograft Dysfunction (EAD) * Discard of a Retrieved Liver * Primary Non-Function (PNF)

Time frame:
10 Days
Reported as:
Count of units · Livers
Number of Livers That Did Not Experience a Safety Event
LiversNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Number of Livers That Did Not Experience a Safety Event147137
SecondaryAssessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay
Time frame:
6 Months
Reported as:
Mean · Days
Assessment of the Health Economic Implications Via Length of ICU Stay and Length of Hospital Stay
DaysNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Length of ICU Stay4.6 ± 7.54.2 ± 6.2
Total Length of Hospital Stay14.3 ± 17.113.3 ± 18.1
SecondaryCompare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire

The EQ-5D-5L Questionnaire is the standard layout for recording an adult person's current self-reported health state. It consists of a standard format for respondents to record their health state according to the EQ-5D-5L descriptive system and the EQ Visual Analog Scale (VAS). EQ-5D-5L index scores range from 0 to 1.0 on a scale where 0 = death and 1.0 = perfect health. EQ-5D-5L is the name of the instrument and is not an acronym.

Time frame:
6 Months
Reported as:
Mean · score on a scale
Compare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire
score on a scaleNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Compare Quality of Life Via the EQ-5D-5L Quality of Life Questionnaire0.9 ± 0.10.8 ± 0.1

Adverse events

Collected over Adverse event data were collected from the point of enrollment through study exit (12 months for subjects completing the study).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Normothermic Machine Perfusion (NMP)10/136 (7.4%)95/136 (69.9%)125/136 (91.9%)
Standard of Care (Ice)4/131 (3.1%)93/131 (71%)123/131 (93.9%)
Most frequent serious events
Showing 10 of 83
Most frequent serious events
EventNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
Biliary Stricture (AnastomoticHepatobiliary disorders17/1367/131
RejectionHepatobiliary disorders8/13616/131
Renal Dysfunction/Acute Kidney InjuryRenal and urinary disorders11/13615/131
Graft DysfunctionHepatobiliary disorders14/1366/131
Bleeding - Transfusion RequiredGeneral disorders8/13612/131
Bleeding Requiring ReoperationGeneral disorders3/13611/131
Blood InfectionInfections and infestations11/1366/131
Other Systemic Disease/EventGeneral disorders9/1362/131
Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders6/1368/131
HyperkalemiaGeneral disorders3/1368/131
Most frequent other events
Showing 10 of 38
Most frequent other events
EventNormothermic Machine Perfusion (NMP)Standard of Care (Ice)
HyperglycemiaEndocrine disorders64/13668/131
Renal Dysfunction/Acute Kidney InjuryRenal and urinary disorders37/13641/131
AnemiaBlood and lymphatic system disorders26/13634/131
LeukopeniaBlood and lymphatic system disorders33/13628/131
Musculoskeletal OtherMusculoskeletal and connective tissue disorders32/13627/131
Other Systemic Disease/EventGeneral disorders18/13629/131
DiarrheaGastrointestinal disorders24/13628/131
Extremities EdemaGeneral disorders29/13628/131
ConstipationGastrointestinal disorders25/13626/131
HypomagnesemiaGeneral disorders24/13626/131

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Normothermic Machine Perfusion (NMP)Standard of Care (Ice)Total
Mean57.4 ± 10.557.2 ± 10.657.3 ± 10.6
Sex: Female, Male
Sex: Female, Male(Participants)Normothermic Machine Perfusion (NMP)Standard of Care (Ice)Total
Female434891
Male9383176
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Normothermic Machine Perfusion (NMP)Standard of Care (Ice)Total
Hispanic or Latino151328
Not Hispanic or Latino121118239
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Normothermic Machine Perfusion (NMP)Standard of Care (Ice)Total
American Indian or Alaska Native000
Asian011
Native Hawaiian or Other Pacific Islander000
Black or African American5914
White127119246
More than one race000
Unknown or Not Reported426
Region of Enrollment
Region of Enrollment(participants)Normothermic Machine Perfusion (NMP)Standard of Care (Ice)Total
United States136131267
08

Study locations

15 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • Mayo Clinic - Phoenix
    Phoenix, Arizona 85054, United States
  • University of Southern California (USC)
    Los Angeles, California 90033, United States
  • University of California - Los Angeles (UCLA)
    Los Angeles, California 90095, United States
  • University of California-San Francisco (UCSF)
    San Francisco, California 94153, United States
  • University of Miami
    Miami, Florida 33136, United States
  • Indiana University
    Indianapolis, Indiana 46202, United States
  • Ochsner
    New Orleans, Louisiana 70121, United States
  • University of Maryland
    Baltimore, Maryland 21201, United States
  • University of Michigan
    Ann Arbor, Michigan 48109, United States
  • Washington University
    Saint Louis, Missouri 63110, United States
  • Duke University
    Durham, North Carolina 27710, United States
  • University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
  • University of Wisconsin Madison
    Madison, Wisconsin 53792, United States
09

References and documents

Publications

  • Kubal C, Mihaylov P, Holden J. Oncologic indications of liver transplantation and deceased donor liver allocation in the United States. Curr Opin Organ Transplant. 2021 Apr 1;26(2):168-175. doi: 10.1097/MOT.0000000000000866. PubMed 33650998 ↗

Study documents

  • Study protocol · Jun 24, 2016
  • Statistical analysis plan · Sep 9, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 29, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02775162
Lead sponsor
OrganOx Ltd.
Collaborators
North American Science Associates Ltd.
Responsible party
Sponsor
First posted
May 17, 2016
Start date
Oct 9, 2016
Primary completion
Feb 10, 2020
Completion
Feb 19, 2021
Results posted
Jul 22, 2022
Last update
Jul 29, 2022

Study contacts

Stuart Knechtle, MD
principal investigator · Duke University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2022. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

OrganOx Ltd.

Start the discussion