End Stage Liver DiseasePhase 1/2NCT03089840
Normothermic Liver Preservation Trial
A Phase 1/2 study testing OrganOx metra in people with End Stage Liver Disease and Liver Diseases, run by University of Alberta at 1 site in Canada.
Trial summary
This trial is to assess the safety and efficacy of normothermic machine perfusion (NMP) as an organ preservation method prior to transplantation using the OrganOx metra™ device. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Liver Disease, Liver Diseases
- What is being tested?
- OrganOx metra
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteCanada
- Study dates
- 24 Feb 2017to 23 Jul 2024
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipient inclusion criteria:
- Adult subjects (age ≥18 years); active on the waiting list for liver transplantation at the University of Alberta Hospital; informed/deferred consent provided.
- Donor liver inclusion criteria:
- Whole livers from deceased donors ≥ 40kg in weight, that are deemed suitable for transplantation as per local and international practice, and at the discretion of the transplanting surgeon.
- Donor livers will be placed on the metra™ device either at the donor hospital, or where more practical, transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then reperfused on metra™ for ≥ 4 hours ('back-to-base' sub-analysis).
- Expanded criteria grafts may include, but not be restricted to the following graft qualities. Such grafts will only be transplanted at the recipient transplant surgeon's discretion, if judged to be safe and appropriate for that individual recipient.
Show all 13Show fewer
- Donation after Neurological Determination of Death (NDD) Expanded Criteria livers may include: ≥60% macro/micro steatosis; cold ischemia > 10 hours; combined steatosis 30-60% and >6hr cold storage; significant liver trauma.
- Donation after Cardio-Circulatory Death (DCD) Expanded Criteria livers may include: Age up to 75; mild steatosis (30%); DCD offers from distant centres; warm time up to 60 min.
- As per standard clinical practice, the on-call recipient transplant surgeon will evaluate donor and graft information, weigh the risks and benefits of graft utilization for a particular recipient, and make the final decision about whether or not to proceed to transplantation. Based on preliminary experience with the metraTM, perfusion parameters may additionally be considered in reaching a decision:
- Normal, stable portal vein flow (≥800-1000ml/minute) and artery flow (≥200ml/minute)
- Falling lactate levels
- Stable perfusate pH within the normal range (7.2 - 7.4) after bicarbonate correction
- Evenly perfused graft on the device
Who cannot join
- Recipient exclusion criteria: Age less than 18 years, allergic to required components of the perfusion solution, refusal of informed consent.
- Donor liver exclusion criteria: Livers from living donors.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessing the Safety and Efficacy of a Portable Ex Vivo Oxygenated, Normothermic Liver Perfusion System (OrganOx Metra™ ) Prior to Liver Transplantation
This trial is to assess the safety and efficacy of normothermic machine perfusion (NMP) as an organ preservation method prior to transplantation using the OrganOx metra™ device.
Read the detailed description
The standard approach for storage and transportation of livers for transplantation involves cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) or alternative solutions, and storage in sterile bags surrounded by preservation solution in a box by ice. The prolonged cold ischemic injury substantially compounds pre-existing donor liver graft injury, further exacerbating potential risk for recipients. Normothermic perfusion may eliminate cold ischemic injury, and provide a unique opportunity to further assess ex vivo function of the most marginal organs before they are transplanted. Being able to select or eliminate organs in this manner would provide additional livers for transplantation while at the same time minimizing risk for recipients.
This non-randomized, open-label, single arm, prospective trial is to assess safety and preliminary efficacy of normothermic machine perfusion on livers accepted under standard and expanded criteria for standard liver transplantation (n=50). Following assessment of donor and recipient eligibility and confirmation of consent, the liver will be preserved on OrganOx metra™ either at the donor hospital or where more practical transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours ('back to base' sub-analysis). At the end of preservation, the liver will be transplanted and the patient managed according to standard local practice and protocols. 100 anonymized patient data from the University of Alberta Hospital Liver Transplant database will be utilized for the matched controls. Enrolled subjects will participate in the study for 30 days (the accrued period to capture primary and secondary end-points: graft and patient survival, graft function, NMP perfusion parameters). Additional routine (non-research) biochemical and survival data will be collected and documented at 3, 6, 9 and 12 months post-transplant. Primary outcomes will be analyzed and reported 30 days following transplantation of the last subject in the study.
- Conditions
- End Stage Liver Disease, Liver Diseases
- Being tested
- OrganOx metra
- Keywords
- normothermic perfusion, liver transplantation
- Medical subject headings
- End Stage Liver Disease, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OrganOx metraDevice
Following the routine retrieval procedure at the donor hospital the liver will be flushed with cold preservation solution and prepared for cannulation. The donor organ is then placed on the OrganOx metra device and will be perfused with warmed solution. The OrganOx metra device containing the donor organ is then transported to the recipient transplant centre. The donor liver is then removed from the device and flushed with standard of care preservation solution. Alternatively, where more practical, the livers will be transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours. Implantation and reperfusion of the liver proceed as per the usual practice of the recipient transplant centre.
| Study group | Role | What they receive |
|---|---|---|
| Normothermic Machine Perfusion (OrganOx metra) | Experimental | Donor livers will be placed on the OrganOx metra device for normothermic perfusion before transplantation. Receives: Device: OrganOx metra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Graft survival rate
Graft survival rate
Measured: Day 30
Secondary outcomes (8)
Patient survival rate
Patient survival rate
Measured: Day 30
Early Allograft Dysfunction (EAD) rate
EAD rate
Measured: Up to Day 7
Peak aspartate transaminase (AST) levels
Peak AST levels in the blood
Measured: Up to Day 7
Daily lactate levels
Daily lactate levels in the blood
Measured: Up to Day 7
Perfusate AST levels
AST levels in perfusate blood
Measured: Day -1 and Day 0
Perfusate alanine transaminase (ALT) levels
ALT levels in perfusate blood
Measured: Day -1 and Day 0
Perfusate bilirubin levels
Bilirubin levels in perfusate blood
Measured: Day -1 and Day 0
Perfusate lactate levels
Lactate levels in perfusate blood
Measured: Day -1 and Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2017
- Study start24 Feb 2017
- Primary completion23 Jul 2024
- Study completion23 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End Stage Liver DiseaseStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Non-randomized, open-label, single arm, prospective trial using retrospective matched controls
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James Shapiro, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03089840
- Sponsor's protocol ID
- Pro00043239
- Status last verified
- Jul 2024
- First submitted
- 11 Mar 2017
- Last updated
- 25 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing the Safety and Efficacy of a Portable Ex Vivo Oxygenated, Normothermic Liver Perfusion System (OrganOx Metra™ ) Prior to Liver Transplantation
- ClinicalTrials.gov ID
- NCT03089840
- Acronym / sponsor ID
- Pro00043239
- Conditions
- End Stage Liver Disease, Liver Diseases
- Keywords
- normothermic perfusion, liver transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 24 Feb 2017 (actual)
- Primary completion
- 23 Jul 2024 (actual)
- Study completion
- 23 Jul 2024 (actual)
- First posted
- 24 Mar 2017 (actual)
- 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.
This trial is to assess the safety and efficacy of normothermic machine perfusion (NMP) as an organ preservation method prior to transplantation using the OrganOx metra™ device.
Detailed description
The standard approach for storage and transportation of livers for transplantation involves cold perfusion with Histidine-tryptophan-ketoglutarate (HTK) or alternative solutions, and storage in sterile bags surrounded by preservation solution in a box by ice. The prolonged cold ischemic injury substantially compounds pre-existing donor liver graft injury, further exacerbating potential risk for recipients. Normothermic perfusion may eliminate cold ischemic injury, and provide a unique opportunity to further assess ex vivo function of the most marginal organs before they are transplanted. Being able to select or eliminate organs in this manner would provide additional livers for transplantation while at the same time minimizing risk for recipients.
This non-randomized, open-label, single arm, prospective trial is to assess safety and preliminary efficacy of normothermic machine perfusion on livers accepted under standard and expanded criteria for standard liver transplantation (n=50). Following assessment of donor and recipient eligibility and confirmation of consent, the liver will be preserved on OrganOx metra™ either at the donor hospital or where more practical transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours ('back to base' sub-analysis). At the end of preservation, the liver will be transplanted and the patient managed according to standard local practice and protocols. 100 anonymized patient data from the University of Alberta Hospital Liver Transplant database will be utilized for the matched controls. Enrolled subjects will participate in the study for 30 days (the accrued period to capture primary and secondary end-points: graft and patient survival, graft function, NMP perfusion parameters). Additional routine (non-research) biochemical and survival data will be collected and documented at 3, 6, 9 and 12 months post-transplant. Primary outcomes will be analyzed and reported 30 days following transplantation of the last subject in the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Non-randomized, open-label, single arm, prospective trial using retrospective matched controls
| Arm | Type | Receives |
|---|---|---|
| Normothermic Machine Perfusion (OrganOx metra) | Experimental | Device: OrganOx metraDonor livers will be placed on the OrganOx metra device for normothermic perfusion before transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Adult subjects (age ≥18 years); active on the waiting list for liver transplantation at the University of Alberta Hospital; informed/deferred consent provided.
- Whole livers from deceased donors ≥ 40kg in weight, that are deemed suitable for transplantation as per local and international practice, and at the discretion of the transplanting surgeon.
- Donor livers will be placed on the metra™ device either at the donor hospital, or where more practical, transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then reperfused on metra™ for ≥ 4 hours ('back-to-base' sub-analysis).
- Expanded criteria grafts may include, but not be restricted to the following graft qualities. Such grafts will only be transplanted at the recipient transplant surgeon's discretion, if judged to be safe and appropriate for that individual recipient.
- Donation after Neurological Determination of Death (NDD) Expanded Criteria livers may include: ≥60% macro/micro steatosis; cold ischemia > 10 hours; combined steatosis 30-60% and >6hr cold storage; significant liver trauma.
Key exclusion criteria (2 listed)
- Recipient exclusion criteria: Age less than 18 years, allergic to required components of the perfusion solution, refusal of informed consent.
- Donor liver exclusion criteria: Livers from living donors.
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 |
|---|---|---|
| OrganOx metraFollowing the routine retrieval procedure at the donor hospital the liver will be flushed with cold preservation solution and prepared for cannulation. The donor organ is then placed on the OrganOx metra device and will be perfused with warmed solution. The OrganOx metra device containing the donor organ is then transported to the recipient transplant centre. The donor liver is then removed from the device and flushed with standard of care preservation solution. Alternatively, where more practical, the livers will be transported to the University of Alberta hospital with ≤ 6 hours of cold storage and then placed on the metra™ for ≥ 4 hours. Implantation and reperfusion of the liver proceed as per the usual practice of the recipient transplant centre. | Device | Normothermic Machine Perfusion (OrganOx metra) |
Primary outcome
Graft survival rate
Time frame: Day 30
Graft survival rate
8 secondary outcomes
Patient survival rate
Time frame: Day 30
Early Allograft Dysfunction (EAD) rate
Time frame: Up to Day 7
Peak aspartate transaminase (AST) levels
Time frame: Up to Day 7
Daily lactate levels
Time frame: Up to Day 7
Perfusate AST levels
Time frame: Day -1 and Day 0
Perfusate alanine transaminase (ALT) levels
Time frame: Day -1 and Day 0
Perfusate bilirubin levels
Time frame: Day -1 and Day 0
Perfusate lactate levels
Time frame: Day -1 and Day 0
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 25 Jul 2024.
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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.
James Shapiro, MD, PhD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing OrganOx metra in people with End Stage Liver Disease and Liver Diseases, run by University of Alberta at 1 site in Canada.
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 13 inclusion and 2 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 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Graft survival rate (time frame: Day 30). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Jul 2024.