Liver TransplantPhase 2/3NCT01884038
Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
A Phase 2/3 study testing treprostinil sodium in people with Liver Transplant, run by United Therapeutics at 1 site in United States.
Trial summary
Patients undergoing orthotopic liver transplant will experience some degree of clinical and/or biochemical hepatic dysfunction. This early injury is known as primary graft dysfunction and varies from minor abnormalities to primary nonfunction. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Transplant
- What is being tested?
- treprostinil sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Jun 2010
- Phase
- Phase 2/3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Accepted as a liver transplant candidate at the University of Pittsburgh Medical Center
- Be receiving a cadaver donor liver transplant
- Treated in accordance with the standard of care protocol(s) in effect for liver transplant recipients at the University of Pittsburgh Medical Center.
Who cannot join
- Receiving a living done liver transplant
- Receiving a donor liver with a cold ischemia time less that 6 hours
- Receiving a donor liver with macrosteatosis greater than 30%
- Receiving any investigation drug with the except of alemtuzamab (Camphath)
- Failed liver transplant in previous 180 days
- Prior organ transplant or cell infusion
- Undergoing multi-organ transplant
- Pregnant or nursing female
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh Medical Center, Starzl Transplantation Institute
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Single Center, Randomized, Double-Blind, Parallel Placebo-Controlled Study of the Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
Patients undergoing orthotopic liver transplant will experience some degree of clinical and/or biochemical hepatic dysfunction. This early injury is known as primary graft dysfunction and varies from minor abnormalities to primary nonfunction. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits.
Read the detailed description
In vitro and in vivo research has consistently demonstrated an array of potential beneficial effects of prostanoids under both immune and non-immune circumstances relevant to liver allografts. (1-3) Recent reviews summarize the pharmacologic rationale and nonclinical and clinical experience supporting for the use of prostanoids, including prostacyclin and its analogs, in reducing early morbidity and mortality associated with liver transplantation. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits. Additionally, the reduction in serum creatinine and reduced need for post-operative dialysis observed in some studies has implications in protecting the kidneys from the nephrotoxic affects of the immunosuppressant agents, especially during the early post-operative period.
As a chemically stable analog of prostacyclin (PGI2), peri-operative intravenous administration of Remodulin is hypothesized to ameliorate or prevent reperfusion damage and thereby decrease hospitalization time and improve the clinical outcome of liver transplantation, compared to placebo control. Remodulin, as a prostanoid, is expected to facilitate restoration of the blood supply to the revascularized graft, and to provide the well-characterized protective effects of this class of compounds in liver transplant patients.
- Conditions
- Liver Transplant
- Being tested
- treprostinil sodium, Placebo
- Keywords
- Liver Transplant, Prostacyclin, Treprostinil sodium, Remodulin, Reperfusion Injury, Primary Nonfunction
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treprostinil sodiumDrug
Also called Remodulin, UT 15
A single dose strength of treprostinil sodium (1.0 mg/mL) and matching placebo will be provided in 20-mL multi-dose vials.
The study drug will be started after induction of anesthesia and increased incrementally to a target dose of 10 ng/kg/min during surgery and 48 hours post-operative
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Remodulin | Experimental | Remodulin initiated as a continuous IV infusion at a dose of 2.5 ng/kg/min after subjects have been assessed as hemodynamically stable in the ICU. Dose may be escalated in 1.25- to 2.5-ng/kg/min increments, up to 7.5 ng/kg/min, with a target dose of 5 ng/kg/min, based on tolerability. The dose will be maintained at the maximum tolerated dose, not to exceed 7.5 ng/kg/min for 5 days after the transplantation surgery. Receives: Drug: treprostinil sodium |
| Placebo | Placebo comparator | Matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Duration of the initial hospitalization (days) following transplantation
Measured: up to 180 days
Area under the curve (AUC) of serum aspartate transaminase (AST) levels.
The difference in serum AST as measured by AUC during the first seven days post-transplant will be compared between placebo and Remodulin treatment groups. AST is a serum transaminase marker of hepatic injury, and the AUC of AST levels represents the total magnitude of injury the liver experiences against time.
Measured: 7 days
Secondary outcomes (9)
Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])
Measured: 7 days
Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure
Measured: 30 days
Graft survival
Measured: 30 days, 90 days and 180 days
Subject survival at
Measured: Day 30, 90, and 180
Post-transplant renal function
Measured: 30 days
Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.
Measured: up to 180 days
Intra-operative blood product usage
Measured: 1 day
Death from any cause
Measured: 180 days
Total costs for initial transplant hospitalization
Measured: up to 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2013 (estimated)
- Study startJun 2008
- Primary completionJun 2010 (estimated)
- Study completionJun 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver TransplantStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Pittsburgh Medical Center
- Responsible party
- Sponsor
- Investigators
- Amadeo Marcos, MD, Principal investigator, University of Pittsburgh Medical CenterRaman Venkataramanan, Ph.D, F.C.P., Principal investigator, University of Pittsburgh Medcial Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01884038
- Sponsor's protocol ID
- RIV-LT-301
- Status last verified
- Jun 2013
- First submitted
- 19 Oct 2012
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Center, Randomized, Double-Blind, Parallel Placebo-Controlled Study of the Safety and Efficacy of Perioperative Remodulin® in Orthotopic Liver Transplant Recipients
- ClinicalTrials.gov ID
- NCT01884038
- Acronym / sponsor ID
- RIV-LT-301
- Conditions
- Liver Transplant
- Keywords
- Liver Transplant, Prostacyclin, Treprostinil sodium, Remodulin, Reperfusion Injury, Primary Nonfunction
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- University of Pittsburgh Medical Center
- Study start
- Jun 2008
- Primary completion
- Jun 2010 (estimated)
- Study completion
- Jun 2010 (estimated)
- First posted
- 21 Jun 2013 (estimated)
- 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.
Patients undergoing orthotopic liver transplant will experience some degree of clinical and/or biochemical hepatic dysfunction. This early injury is known as primary graft dysfunction and varies from minor abnormalities to primary nonfunction. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits.
Detailed description
In vitro and in vivo research has consistently demonstrated an array of potential beneficial effects of prostanoids under both immune and non-immune circumstances relevant to liver allografts. (1-3) Recent reviews summarize the pharmacologic rationale and nonclinical and clinical experience supporting for the use of prostanoids, including prostacyclin and its analogs, in reducing early morbidity and mortality associated with liver transplantation. Prostaglandin-class drugs, including prostacyclin and its analogs, could represent an important advance toward the goal of reducing transplant related morbidity, mortality and associated costs by providing these benefits. Additionally, the reduction in serum creatinine and reduced need for post-operative dialysis observed in some studies has implications in protecting the kidneys from the nephrotoxic affects of the immunosuppressant agents, especially during the early post-operative period.
As a chemically stable analog of prostacyclin (PGI2), peri-operative intravenous administration of Remodulin is hypothesized to ameliorate or prevent reperfusion damage and thereby decrease hospitalization time and improve the clinical outcome of liver transplantation, compared to placebo control. Remodulin, as a prostanoid, is expected to facilitate restoration of the blood supply to the revascularized graft, and to provide the well-characterized protective effects of this class of compounds in liver transplant patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Remodulin | Experimental | Drug: treprostinil sodiumRemodulin initiated as a continuous IV infusion at a dose of 2.5 ng/kg/min after subjects have been assessed as hemodynamically stable in the ICU. Dose may be escalated in 1.25- to 2.5-ng/kg/min increments, up to 7.5 ng/kg/min, with a target dose of 5 ng/kg/min, based on tolerability. The dose will be maintained at the maximum tolerated dose, not to exceed 7.5 ng/kg/min for 5 days after the transplantation surgery. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Accepted as a liver transplant candidate at the University of Pittsburgh Medical Center
- Be receiving a cadaver donor liver transplant
- Treated in accordance with the standard of care protocol(s) in effect for liver transplant recipients at the University of Pittsburgh Medical Center.
Key exclusion criteria (8 listed)
- Receiving a living done liver transplant
- Receiving a donor liver with a cold ischemia time less that 6 hours
- Receiving a donor liver with macrosteatosis greater than 30%
- Receiving any investigation drug with the except of alemtuzamab (Camphath)
- Failed liver transplant in previous 180 days
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 |
|---|---|---|
| treprostinil sodiumAlso: Remodulin, UT 15A single dose strength of treprostinil sodium (1.0 mg/mL) and matching placebo will be provided in 20-mL multi-dose vials. The study drug will be started after induction of anesthesia and increased incrementally to a target dose of 10 ng/kg/min during surgery and 48 hours post-operative | Drug | Remodulin |
| Placebo | Drug | Placebo |
Primary outcome
Duration of the initial hospitalization (days) following transplantation
Time frame: up to 180 days
Area under the curve (AUC) of serum aspartate transaminase (AST) levels.
Time frame: 7 days
The difference in serum AST as measured by AUC during the first seven days post-transplant will be compared between placebo and Remodulin treatment groups. AST is a serum transaminase marker of hepatic injury, and the AUC of AST levels represents the total magnitude of injury the liver experiences against time.
9 secondary outcomes
Serum AST and alanine transaminase (ALT ) levels after transplant (Peak and Area Under the Curve [AUC])
Time frame: 7 days
Primary allograft nonfunction defined as patient death or retransplant within 30 days due to liver failure
Time frame: 30 days
Graft survival
Time frame: 30 days, 90 days and 180 days
Subject survival at
Time frame: Day 30, 90, and 180
Post-transplant renal function
Time frame: 30 days
Duration of time spent in the intensive care unit (ICU; days) during the initial hospitalization.
Time frame: up to 180 days
Intra-operative blood product usage
Time frame: 1 day
Death from any cause
Time frame: 180 days
Total costs for initial transplant hospitalization
Time frame: up to 180 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
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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.
Amadeo Marcos, MD principal investigator
University of Pittsburgh Medical Center
Raman Venkataramanan, Ph.D, F.C.P. principal investigator
University of Pittsburgh Medcial Center
1 site 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 treprostinil sodium in people with Liver Transplant, run by United Therapeutics 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 8 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: withdrawn, as of the sponsor's last update on 19 Dec 2023. 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Duration of the initial hospitalization (days) following transplantation (time frame: up to 180 days). The study lists 2 primary outcomes in all. 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 19 Dec 2023.