Liver TransplantationNCT00948194
Effect of Nitric Oxide (NO) on Ischemic/Reperfusion Injury During Extended Donor Criteria (EDC) Liver Transplantation
A study testing Nitric Oxide in people with Liver Transplantation and Ischemia/Reperfusion Injury, run by University of Colorado, Denver at 1 site in United States.
Trial summary
In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria(EDC)liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Liver Transplantation, Ischemia/Reperfusion Injury, Oxidative Injury
- What is being tested?
- Nitric Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Dec 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 - 69 years of age
- moderate to severe liver disease (MELD score 22 to 30)
- is receiving a extended donor criteria liver graft
Who cannot join
- undergoing multi-organ transplant
- 70 years or older
- diagnosed with hepatocarcinoma
- diagnosed with either hepatopulmonary syndrome or pulmonary hypertension
- pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Hospital
Aurora, Colorado, 80045
About this study
Official title: Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation
In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria(EDC)liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft.
In reviewing the literature, no uniform extended criteria donor classification exists. The characteristics most associated with liver graft failure appear to be cold ischemia time greater than 10 hours, warm ischemia time greater than 40 minutes, donor age > 55 years of age, donor hospitalization > 5 days, a donation after cardiac death (DCD) graft, and a split graft. The researchers will exclude warm ischemia time as this is impossible to predict prior to the transplantation. Any donor meeting at least one of the other criteria will be classified as an EDC donor.
Read more
Hypothesis 1: Inhaled nitric oxide will improve overall outcome of liver recipients after EDC liver transplantation
- Suppression of oxidative injury will improve graft function postoperatively as measured by International Normalized Ratio (INR) bilirubin, transaminases, and duration of hospital stay.
Hypothesis 2: The mechanisms of therapeutic efficacy of inhaled nitric oxide is based on reduction in post-reperfusion oxidative injury as readily measured by the detectable changes in the protein and metabolic profiles in plasma of patients treated with inhaled-NO
- Nuclear Magnetic Resonance (NMR)-based metabolic markers (xanthine end-products, lactate, and hepatic osmolytes) that are consistent with acute liver injury will be decreased in NO-treated recipients.
- Protein markers of reperfusion injury (argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1) will be greater in the plasma of patients who are not treated with inhaled-NO
- Reduced oxidative injury will be reflected by a decrease in the number of mitochondrial peroxiredoxins isoforms and the number that are oxidized in NO-treated liver recipients.
- Being tested
- Nitric Oxide
- Keywords
- Extended Donor Criteria
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Also called INOmax
Inhalation - 40 ppm, at the initiation of anesthesia to the end of surgery
| Study group | Role | What they receive |
|---|---|---|
| No nitric oxide | No intervention | This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics |
| Nitric Oxide | Experimental | Will receive Nitric oxide and other standard inhaled anesthetics Receives: Drug: Nitric Oxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Determine if Inhaled Nitric Oxide Has Beneficial Effects on Overall Outcome After Extended Criteria Donor (EDC) Liver Transplantation
Measured: 3 years
Secondary outcomes (2)
To Construct a Plasma Metabolic/Protein Profile of I/R Injury in Transplanted Livers
Measured: 3 years
To Examine the Effects of Nitric Oxide on Protein Synthesis and Metabolism Following Extended Criteria Donor Liver Transplantation
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2009 (estimated)
- Study startOct 2009
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: This study was terminated when the P.I. left the university.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver TransplantationStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew J. Fiegel, M.D., Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00948194
- Sponsor's protocol ID
- 09-0137
- Status last verified
- May 2021
- First submitted
- 24 Jul 2009
- Last updated
- 28 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Effect of Nitric Oxide on Ischemic Reperfusion Injury During Extended Donor Criteria Liver Transplantation
- ClinicalTrials.gov ID
- NCT00948194
- Acronym / sponsor ID
- 09-0137
- Keywords
- Extended Donor Criteria
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated when the P.I. left the university.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 29 Jul 2009 (estimated)
- Results
- Posted 28 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study, the researchers propose to investigate the efficacy of inhaled nitric oxide to prevent ischemia-reperfusion (I/R) hepatocyte injury in patients who receive extended donor criteria(EDC)liver grafts based on changes in proteomic and metabolomic markers following revascularization of the donor graft.
In reviewing the literature, no uniform extended criteria donor classification exists. The characteristics most associated with liver graft failure appear to be cold ischemia time greater than 10 hours, warm ischemia time greater than 40 minutes, donor age > 55 years of age, donor hospitalization > 5 days, a donation after cardiac death (DCD) graft, and a split graft. The researchers will exclude warm ischemia time as this is impossible to predict prior to the transplantation. Any donor meeting at least one of the other criteria will be classified as an EDC donor.
Hypothesis 1: Inhaled nitric oxide will improve overall outcome of liver recipients after EDC liver transplantation
- Suppression of oxidative injury will improve graft function postoperatively as measured by International Normalized Ratio (INR) bilirubin, transaminases, and duration of hospital stay.
Hypothesis 2: The mechanisms of therapeutic efficacy of inhaled nitric oxide is based on reduction in post-reperfusion oxidative injury as readily measured by the detectable changes in the protein and metabolic profiles in plasma of patients treated with inhaled-NO
- Nuclear Magnetic Resonance (NMR)-based metabolic markers (xanthine end-products, lactate, and hepatic osmolytes) that are consistent with acute liver injury will be decreased in NO-treated recipients.
- Protein markers of reperfusion injury (argininosuccinate synthase (ASS) and estrogen sulfotransferase (EST-1) will be greater in the plasma of patients who are not treated with inhaled-NO
- Reduced oxidative injury will be reflected by a decrease in the number of mitochondrial peroxiredoxins isoforms and the number that are oxidized in NO-treated liver recipients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No nitric oxide | No intervention | –This arm will not receive nitric oxide, but will receive other standard inhaled anesthetics |
| Nitric Oxide | Experimental | Drug: Nitric OxideWill receive Nitric oxide and other standard inhaled anesthetics |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18 - 69 years of age
- moderate to severe liver disease (MELD score 22 to 30)
- is receiving a extended donor criteria liver graft
Key exclusion criteria (5 listed)
- undergoing multi-organ transplant
- 70 years or older
- diagnosed with hepatocarcinoma
- diagnosed with either hepatopulmonary syndrome or pulmonary hypertension
- pregnant
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 |
|---|---|---|
| Nitric OxideAlso: INOmaxInhalation - 40 ppm, at the initiation of anesthesia to the end of surgery | Drug | Nitric Oxide |
Primary outcome
To Determine if Inhaled Nitric Oxide Has Beneficial Effects on Overall Outcome After Extended Criteria Donor (EDC) Liver Transplantation
Time frame: 3 years
2 secondary outcomes
To Construct a Plasma Metabolic/Protein Profile of I/R Injury in Transplanted Livers
Time frame: 3 years
To Examine the Effects of Nitric Oxide on Protein Synthesis and Metabolism Following Extended Criteria Donor Liver Transplantation
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Matthew J. Fiegel, M.D. principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitric Oxide in people with Liver Transplantation and Ischemia/Reperfusion Injury, run by University of Colorado, Denver at 1 site in United States.
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 3 inclusion and 5 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: stopped early, as of the sponsor's last update on 28 May 2021. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
To Determine if Inhaled Nitric Oxide Has Beneficial Effects on Overall Outcome After Extended Criteria Donor (EDC) Liver Transplantation (time frame: 3 years). 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 28 May 2021.