Reperfusion InjuryPhase 2/3NCT00582010
Study to Evaluate if Inhaled Nitric Oxide Improves Liver Function After Transplantation
A Phase 2/3 study testing inhaled nitric oxide and nitrogen gas in people with Reperfusion Injury and Liver Injury, run by University of Alabama at Birmingham at 2 sites in United States.
Trial summary
This blinded, placebo-controlled study will administer inhaled nitric oxide to patients undergoing liver transplantation. The purpose of the study is to test if inhaled nitric oxide prevents liver injury associated with the restoration of blood flow. Read more about this study
- Who is it for?
- Ages 19 to 80 years
- Conditions the study is for
- Reperfusion Injury, Liver Injury
- What is being tested?
- inhaled nitric oxide and nitrogen gas
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2008to Oct 2012
- Phase
- Phase 2/3
- 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 19 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients > 19 yr of age scheduled to undergo liver transplantation.
Who cannot join
- Patients < 19 yr of age
- Patients undergoing re-transplantation or dual organ transplantation
- Patients with underlying pulmonary complications
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
University of Washington
Seattle, Washington, 98195-6540
About this study
Official title: Effects of Inhaled Nitric Oxide on Ischemia-Reperfusion Injury in Human Liver During Transplantation
This blinded, placebo-controlled study will administer inhaled nitric oxide to patients undergoing liver transplantation. The purpose of the study is to test if inhaled nitric oxide prevents liver injury associated with the restoration of blood flow. The premise of the current study is provided by previous studies which document a protective effect of inhaled nitric oxide in this clinical setting.
Read the detailed description
Specifically, presenting ischemia-reperfusion injury to transplanted livers remains a therapeutic goal in improving liver function and potentially expanding the number of transplantable livers. This study aims to assess the efficacy of inhaled nitric oxide to limit ischemia-reperfusion injury in transplanted livers and by doing so improve liver function post transplantation and decrease patient hospital length of stays.
- Conditions
- Reperfusion Injury, Liver Injury
- Being tested
- inhaled nitric oxide, nitrogen gas
- Keywords
- ischemia-reperfusion, nitric oxide, inflammation, cell-death, Liver-function post transplantation
- Medical subject headings
- Reperfusion Injury, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inhaled nitric oxideDrug
Also called iNO
inhaled 80ppm for duration of surgery.
nitrogen gasDrug
inhaled
| Study group | Role | What they receive |
|---|---|---|
| 1. Experimental | Experimental | iNO administration Receives: Drug: inhaled nitric oxide |
| 2. Placebo | Placebo comparator | Placebo (nitrogen) Receives: Drug: nitrogen gas |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels)
The faster the percent decrease of AST reflect the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. The rate was calculated by measuring AST levels at baseline and at 96 hours post baseline. (AST levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of AST relative to baseline).
Measured: baseline and 96 hours after baseline
Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels)
The faster the percent decrease ALT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. . (ALT levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of ALT relative to baseline).
Measured: baseline and 96 hours after baseline
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels)
The faster the percent increase of alkaline phosphatase reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an increase; a negative percentage reflects a decrease.
Measured: baseline and 96 hours after baseline
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT))
The faster the percent increase of PT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase.
Measured: baseline and 96 hours after baseline
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels)
A positive percent reflects an decrease; a negative percentage reflects a increase.
Measured: baseline and 96 hours after baseline
Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications)
Number of complications due to hepatobiliary events.
Measured: baseline to 9 months after transplantation
Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery
Number of any complication reported by subjects at 9 months after surgery
Measured: baseline to 9 months post surgery
Secondary outcomes (2)
Effect of iNO on Hosptial Length of Stay
number of days subject in hospital after surgery until discharge
Measured: from surgery through discharge from hospital
Effect of iNO on SICU Stay
Number of minutes after surgery subject remained in SICU
Measured: baseline to discharge for SICU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2007 (estimated)
- Study startApr 2008
- Primary completionMar 2009
- Study completionOct 2012
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Reperfusion InjuryStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Mallinckrodt, University of Washington
- Responsible party
- Principal investigator, Rakesh Patel, University of Alabama at Birmingham
- Investigators
- Rakesh P Patel, PhD, Principal investigator, University of Alabama at BirminghamKeith A Jones, MD, Principal investigator, University of Alabama at BirminghamDevin E Eckhoff, MD, Principal investigator, University of Alabama at BirminghamJohn S Bynon, MD, Study director, University of Alabama at BirminghamBlair Smith, MD, Study director, University of Alabama at BirminghamClark Cross, MD, Study chair, University of Alabama at BirminghamLuc Frenette, MD, Study director, University of Alabama at BirminghamJohn D Lang, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00582010
- Sponsor's protocol ID
- F070112003
- Status last verified
- Oct 2014
- First submitted
- 20 Dec 2007
- Last updated
- 6 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest. 2007 Sep;117(9):2583-91. doi: 10.1172/JCI31892.
PubMed 17717604Lang JD Jr, Smith AB, Brandon A, Bradley KM, Liu Y, Li W, Crowe DR, Jhala NC, Cross RC, Frenette L, Martay K, Vater YL, Vitin AA, Dembo GA, Dubay DA, Bynon JS, Szychowski JM, Reyes JD, Halldorson JB, Rayhill SC, Dick AA, Bakthavatsalam R, Brandenberger J, Broeckel-Elrod JA, Sissons-Ross L, Jordan T, Chen LY, Siriussawakul A, Eckhoff DE, Patel RP. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One. 2014 Feb 12;9(2):e86053. doi: 10.1371/journal.pone.0086053. eCollection 2014.
PubMed 24533048
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Inhaled Nitric Oxide on Ischemia-Reperfusion Injury in Human Liver During Transplantation
- ClinicalTrials.gov ID
- NCT00582010
- Acronym / sponsor ID
- F070112003
- Conditions
- Reperfusion Injury, Liver Injury
- Keywords
- ischemia-reperfusion, nitric oxide, inflammation, cell-death, Liver-function post transplantation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Mallinckrodt, University of Washington
- Study start
- Apr 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 28 Dec 2007 (estimated)
- Results
- Posted 6 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This blinded, placebo-controlled study will administer inhaled nitric oxide to patients undergoing liver transplantation. The purpose of the study is to test if inhaled nitric oxide prevents liver injury associated with the restoration of blood flow. The premise of the current study is provided by previous studies which document a protective effect of inhaled nitric oxide in this clinical setting.
Detailed description
Specifically, presenting ischemia-reperfusion injury to transplanted livers remains a therapeutic goal in improving liver function and potentially expanding the number of transplantable livers. This study aims to assess the efficacy of inhaled nitric oxide to limit ischemia-reperfusion injury in transplanted livers and by doing so improve liver function post transplantation and decrease patient hospital length of stays.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1. Experimental | Experimental | Drug: inhaled nitric oxideiNO administration |
| 2. Placebo | Placebo comparator | Drug: nitrogen gasPlacebo (nitrogen) |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients > 19 yr of age scheduled to undergo liver transplantation.
Key exclusion criteria (3 listed)
- Patients < 19 yr of age
- Patients undergoing re-transplantation or dual organ transplantation
- Patients with underlying pulmonary complications
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 |
|---|---|---|
| inhaled nitric oxideAlso: iNOinhaled 80ppm for duration of surgery. | Drug | 1. Experimental |
| nitrogen gasinhaled | Drug | 2. Placebo |
Primary outcome
Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels)
Time frame: baseline and 96 hours after baseline
The faster the percent decrease of AST reflect the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. The rate was calculated by measuring AST levels at baseline and at 96 hours post baseline. (AST levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of AST relative to baseline).
Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in ALT Levels)
Time frame: baseline and 96 hours after baseline
The faster the percent decrease ALT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase. . (ALT levels were lower at 96 hours relative to baseline- positive values in data table indicate percent decrease of ALT relative to baseline).
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Alkaline Phosphatase Levels)
Time frame: baseline and 96 hours after baseline
The faster the percent increase of alkaline phosphatase reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an increase; a negative percentage reflects a decrease.
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Prothrombin Times (PT))
Time frame: baseline and 96 hours after baseline
The faster the percent increase of PT reflect, the greater the treatment improved liver function post transplant. A positive percent reflects an decrease; a negative percentage reflects a increase.
Change in Rate of Liver Function Recovery Post-transplantation (Percent Change in Bilirubin Levels)
Time frame: baseline and 96 hours after baseline
A positive percent reflects an decrease; a negative percentage reflects a increase.
Change in Rate of Liver Function Recovery Post-transplantation (Decrease in Hepatobiliary Complications)
Time frame: baseline to 9 months after transplantation
Number of complications due to hepatobiliary events.
Number of Complications Related to Liver Function Recovery Post-transplantation (Total Complications) at 9 Months Post Surgery
Time frame: baseline to 9 months post surgery
Number of any complication reported by subjects at 9 months after surgery
2 secondary outcomes
Effect of iNO on Hosptial Length of Stay
Time frame: from surgery through discharge from hospital
Effect of iNO on SICU Stay
Time frame: baseline to discharge for SICU
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17717604Lang JD Jr, Teng X, Chumley P, Crawford JH, Isbell TS, Chacko BK, Liu Y, Jhala N, Crowe DR, Smith AB, Cross RC, Frenette L, Kelley EE, Wilhite DW, Hall CR, Page GP, Fallon MB, Bynon JS, Eckhoff DE, Patel RP. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest. 2007 Sep;117(9):2583-91. doi: 10.1172/JCI31892.
- Derived from this study: PubMed 24533048Lang JD Jr, Smith AB, Brandon A, Bradley KM, Liu Y, Li W, Crowe DR, Jhala NC, Cross RC, Frenette L, Martay K, Vater YL, Vitin AA, Dembo GA, Dubay DA, Bynon JS, Szychowski JM, Reyes JD, Halldorson JB, Rayhill SC, Dick AA, Bakthavatsalam R, Brandenberger J, Broeckel-Elrod JA, Sissons-Ross L, Jordan T, Chen LY, Siriussawakul A, Eckhoff DE, Patel RP. A randomized clinical trial testing the anti-inflammatory effects of preemptive inhaled nitric oxide in human liver transplantation. PLoS One. 2014 Feb 12;9(2):e86053. doi: 10.1371/journal.pone.0086053. eCollection 2014.
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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.
Rakesh P Patel, PhD principal investigator
University of Alabama at Birmingham
Keith A Jones, MD principal investigator
University of Alabama at Birmingham
Devin E Eckhoff, MD principal investigator
University of Alabama at Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing inhaled nitric oxide and nitrogen gas in people with Reperfusion Injury and Liver Injury, run by University of Alabama at Birmingham at 2 sites 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 1 inclusion and 3 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 6 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Nov 2014). 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?
Changed Rate of Liver Function Recovery Post-transplantation (Percent Change in AST Levels) (time frame: baseline and 96 hours after baseline). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00582010, which also lists 2 linked publications.
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 6 Nov 2014.