Ischemia Reperfusion InjuryPhase 1NCT01481974
Safety and Efficacy of Treprostinil in Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplantation
A Phase 1 study testing Treprostinil in people with Ischemia Reperfusion Injury, run by Abhinav Humar, MD at 2 sites in United States.
Trial summary
The overall purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of a five-days post-operative course of Treprostinil in liver transplant patients. The hypothesis of this study is that Treprostinil can be safely administered post-operatively in liver transplant patients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Ischemia Reperfusion Injury
- What is being tested?
- Treprostinil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2012to 24 Nov 2019
- Phase
- Phase 1
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have signed appropriate informed consent.
- Be between 18 years and 65 years of age.
- Have been accepted as a liver transplant candidate at the University of Pittsburgh Medical center (UPMC).
- Be receiving a cadaver donor liver transplant.
- Be treated in accordance with the standard of care protocol(s) currently in effect for liver transplant recipients at the UPMC, including immunosuppression and other elements of pre- and post-operative care.
Who cannot join
- Subjects must not:
- Be receiving a living donor liver transplant.
- Be receiving a donor liver with a cold ischemia time less than 5 hours or greater than 12 hours.
- Be receiving any investigational drug (a drug other than Treprostinil administered under an IND) or participating in any other investigational study, with the exception of alemtuzumab (Campath).
- Be receiving any prostanoid to treat portopulmonary hypertension.
- Have had a failed liver transplant within the previous 180 days.
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- Be undergoing multi-organ transplantation (transplantation of organs other than liver at the same time as the liver transplantation procedure).
- Have fulminant hepatic failure
- Model for end stage liver diseases (MELD) score of > 40
- Hepatitis C positive donor liver
- On renal replacement therapy at the time of study
- Be receiving any non-standard immunosuppression protocol or other non-standard treatment that could affect interpretation of the study results.
- Those currently receiving treatment for portopulmonary hypertension.
- Those with significant cardiovascular disease including treatment with inotropes.
- Have any known hypersensitivity to prostaglandins, prostacyclin or treprostinil.
- If female, be pregnant or nursing (as confirmed by urine pregnancy test at Baseline).
- HIV positive
- Individuals who are allergic to iodine
- Individuals who are receiving methylene blue
- A donor liver with macrosteatosis greater than 40% if biopsy results are available
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Abhinav Humar
Pittsburgh, Pennsylvania, 15261
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15261
About this study
Official title: An Evaluation of the Safety and Preliminary Efficacy of Perioperative Treprostinil in Preventing Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients
The overall purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of a five-days post-operative course of Treprostinil in liver transplant patients.
The hypothesis of this study is that Treprostinil can be safely administered post-operatively in liver transplant patients. Once safety is documented future studies will address its ability to ameliorate or prevent reperfusion mediated dysfunction of the liver graft and thereby reduce morbidity, leading to shorter hospital stays as compared to historical controls.
Read the detailed description
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 minimizing the effect of ischemia and re perfusion injury of the liver graft. 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. Routine use of prostaglandins (PGE1 and PGI2), however, was limited by its instability and short half life.
Treprostinil, as a prostanoid (prostacyclin analog), is expected to facilitate restoration of the blood supply to the revascularized graft and provide the well-characterized protective effects of this class of compounds in liver transplant patients. Treprostinil has the advantage of a longer elimination half-life than other prostanoids previously tested in these patients. Treprostinil is expected to significantly protect the graft from ischemia and re perfusion injury.
This is a pilot study to evaluate the safety, pharmacokinetics and preliminary efficacy of Treprostinil in orthotopic liver transplant patients as a first step to evaluate its use in prevention of ischemia and reperfusion injury of the grafted liver.
- Conditions
- Ischemia Reperfusion Injury
- Being tested
- Treprostinil
- Keywords
- liver transplantation, treprostinil
- Medical subject headings
- Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TreprostinilDrug
Also called Brand name: REMODULIN
The Treatment Phase will begin at the initiation of Treprostinil after induction of anesthesia for the transplant surgery and continues throughout the surgery and for approximately a total of 120 hours.
Treatment phase activities include:
- Initiation of Treprostinil after the patient is hemodynamically stable following transplant surgery. (Treprostinil dosing will follow a standard 3 + 3 phase 1 design.
| Study group | Role | What they receive |
|---|---|---|
| Treprostinil | Experimental | This is a single center, open-label, dose-escalation Phase I/II study of Treprostinil. Receives: Drug: Treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum ALT concentration after treprostinil treatment in liver transplant patients
The liver injury marker such as alanine aminotransferase (ALT) will be measured in order to evaluate the protective effect of treprostinil in liver transplant recipients.
Measured: Day 7
Secondary outcomes (1)
Pharmacokinetics of treprostinil in liver transplant patients
Clearance and half life
Measured: 0, 2, 4, 6, 12, 18, 24, 30, 36, 42, 48, 72, 96 and 120 hrs during therapy and approximately 0.5, 1, 2, 4, 6, 8, 12 and 24 hr post study drug termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2011 (estimated)
- Study startDec 2012
- Primary completion18 May 2019
- Study completion24 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemia Reperfusion InjuryStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abhinav Humar, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Abhinav Humar, MD, University of Pittsburgh
- Investigators
- Abhinav Humar, M.D., Principal investigator, University of Pittsburgh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01481974
- Sponsor's protocol ID
- STUDY19100094
- Status last verified
- Dec 2023
- First submitted
- 20 Oct 2011
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Evaluation of the Safety and Preliminary Efficacy of Perioperative Treprostinil in Preventing Ischemia and Reperfusion Injury in Adult Orthotopic Liver Transplant Recipients
- ClinicalTrials.gov ID
- NCT01481974
- Acronym / sponsor ID
- STUDY19100094
- Conditions
- Ischemia Reperfusion Injury
- Keywords
- liver transplantation, treprostinil
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Abhinav Humar, MDUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- 18 May 2019 (actual)
- Study completion
- 24 Nov 2019 (actual)
- First posted
- 30 Nov 2011 (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.
The overall purpose of this study is to evaluate the safety, pharmacokinetics and preliminary efficacy of a five-days post-operative course of Treprostinil in liver transplant patients.
The hypothesis of this study is that Treprostinil can be safely administered post-operatively in liver transplant patients. Once safety is documented future studies will address its ability to ameliorate or prevent reperfusion mediated dysfunction of the liver graft and thereby reduce morbidity, leading to shorter hospital stays as compared to historical controls.
Detailed description
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 minimizing the effect of ischemia and re perfusion injury of the liver graft. 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. Routine use of prostaglandins (PGE1 and PGI2), however, was limited by its instability and short half life.
Treprostinil, as a prostanoid (prostacyclin analog), is expected to facilitate restoration of the blood supply to the revascularized graft and provide the well-characterized protective effects of this class of compounds in liver transplant patients. Treprostinil has the advantage of a longer elimination half-life than other prostanoids previously tested in these patients. Treprostinil is expected to significantly protect the graft from ischemia and re perfusion injury.
This is a pilot study to evaluate the safety, pharmacokinetics and preliminary efficacy of Treprostinil in orthotopic liver transplant patients as a first step to evaluate its use in prevention of ischemia and reperfusion injury of the grafted liver.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treprostinil | Experimental | Drug: TreprostinilThis is a single center, open-label, dose-escalation Phase I/II study of Treprostinil. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Have signed appropriate informed consent.
- Be between 18 years and 65 years of age.
- Have been accepted as a liver transplant candidate at the University of Pittsburgh Medical center (UPMC).
- Be receiving a cadaver donor liver transplant.
- Be treated in accordance with the standard of care protocol(s) currently in effect for liver transplant recipients at the UPMC, including immunosuppression and other elements of pre- and post-operative care.
Key exclusion criteria (20 listed)
- Be receiving a living donor liver transplant.
- Be receiving a donor liver with a cold ischemia time less than 5 hours or greater than 12 hours.
- Be receiving any investigational drug (a drug other than Treprostinil administered under an IND) or participating in any other investigational study, with the exception of alemtuzumab (Campath).
- Be receiving any prostanoid to treat portopulmonary hypertension.
- Have had a failed liver transplant within the 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 |
|---|---|---|
| TreprostinilAlso: Brand name: REMODULINThe Treatment Phase will begin at the initiation of Treprostinil after induction of anesthesia for the transplant surgery and continues throughout the surgery and for approximately a total of 120 hours. Treatment phase activities include: • Initiation of Treprostinil after the patient is hemodynamically stable following transplant surgery. (Treprostinil dosing will follow a standard 3 + 3 phase 1 design. | Drug | Treprostinil |
Primary outcome
Serum ALT concentration after treprostinil treatment in liver transplant patients
Time frame: Day 7
The liver injury marker such as alanine aminotransferase (ALT) will be measured in order to evaluate the protective effect of treprostinil in liver transplant recipients.
1 secondary outcome
Pharmacokinetics of treprostinil in liver transplant patients
Time frame: 0, 2, 4, 6, 12, 18, 24, 30, 36, 42, 48, 72, 96 and 120 hrs during therapy and approximately 0.5, 1, 2, 4, 6, 8, 12 and 24 hr post study drug termination
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 15 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.
Abhinav Humar, M.D. principal investigator
University of Pittsburgh Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treprostinil in people with Ischemia Reperfusion Injury, run by Abhinav Humar, MD 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 5 inclusion and 20 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 15 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 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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?
Serum ALT concentration after treprostinil treatment in liver transplant patients (time frame: Day 7). 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 15 Dec 2023.