Portopulmonary HypertensionNCT01028651
A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
An observational study of Portopulmonary Hypertension and Pulmonary Arterial Hypertension, run by United Therapeutics at 4 sites in United States.
Trial summary
This was a multicenter, prospective, observational, open-label study. Patients meeting inclusion/exclusion criteria received treatment with treprostinil as recommended by their treating physicians and were followed according to standard of care. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Portopulmonary Hypertension, Pulmonary Arterial Hypertension, Pulmonary Hypertension
- What is being tested?
- Treprostinil
- Type of treatment
- Injection or infusion
- How many people
- 13 participants
- Where
- 4 sitesUnited States
- Study dates
- Jan 2011to Apr 2013
- Phase
- Observational
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.
Who may be able to join
- Patients must:
- Had portal hypertension.
- Be otherwise suitable candidates for OLT.
- Had severe pulmonary arterial hypertension (PAH) defined as a resting mean pulmonary arterial pressure (mPAP) >35 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood Units (WU) by right heart catheterization (RHC) performed as part of standard of care evaluation within 90 days of enrollment.
- Treprostinil therapy must be recommended by the treating physician per standard of care.
- Be NYHA Functional Class II, III, or IV.
- Had pulmonary capillary wedge (PCW) pressure ≤18 mmHg and transpulmonary gradient (TPG) ≥15 mmHg.
Who cannot join
- Patients must not:
- Had received any any investigational therapy as part of a clinical trial for any indication within 30 days prior to enrollment.
- Had a change in dose of treatment for PAH (bosentan [Tracleer], ambrisentan [Letairis], tadalafil [Adcirca], or sildenafil [Revatio]), within 30 days prior to enrollment. That is, subjects may have been treated with any of these agents provided the dose was stable for at least 30 days prior to enrollment.
- Had renal failure requiring hemodialysis.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory Univeristy
Atlanta, Georgia, 30322
Brigham and Women's Hospital
Boston, Massachusetts, 02115
University of Texas, Southwestern Medical Center
Dallas, Texas, 75235
University of California, Los Angeles
Los Angeles, California, 90024
About this study
Official title: An Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
This was a multicenter, prospective, observational, open-label study. Patients meeting inclusion/exclusion criteria received treatment with treprostinil as recommended by their treating physicians and were followed according to standard of care. This observational study collected clinical data and biologic specimens from patients who were treated for portopulmonary hypertension (PoPH), with a goal of achieving hemodynamic parameters appropriate for orthotopic liver transplantation candidacy, including mean pulmonary arterial pressure (mPAP) less than 35 mmHg and pulmonary vascular resistance (PVR) less than 3 Wood-units (WU) at Week 24 in patients with severe PoPH.
Read the detailed description
Treprostinil is approved as a continuous subcutaneous (SC) or intravenous (IV) infusion by the FDA for the treatment of WHO group I PAH with New York Heart Association (NYHA) Functional Class II, III or IV symptomatology. To date, treprostinil has not been studied in the setting of PoPH; however, it is commonly prescribed in this setting. This was an observational, open-label, multicenter study which documented the safety and efficacy profile of this agent in PoPH to facilitate orthotopic liver transplantation (OLT).
- Being tested
- Treprostinil
- Keywords
- PAH, Pulmonary Hypertension, Remodulin, Treprostinil, Quality of Life
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TreprostinilDrug
Also called Remodulin
Remodulin is supplied in concentrations of 1, 2.5 , 5, and 10 mg/mL and can be administered as supplied or diluted for intravenous (IV) infusion prior to administration.
Remodulin is indicated for subcutaneous (SC) or IV use only as a continuous infusion. Remodulin is preferably infused subcutaneously, but can be administered by a central IV line if the SC route is not tolerated. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min.
| Study group | Role | What they receive |
|---|---|---|
| Portopulmonary hypertension | Not described Receives: Drug: Treprostinil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.
The primary efficacy endpoint was the number of subjects who achieved a mean pulmonary arterial pressure (mPAP) less than 35 mmHg and a pulmonary vascular resistance (PVR) less than 3 Wood units (WU) at Week 24 in patients with severe portopulmonary hypertension (PoPH).
Measured: 24 Weeks
Secondary outcomes (12)
Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24
The change in hemodynamic parameters (including systolic pulmonary arterial pressure [PAPs], diastolic pulmonary arterial pressure [PAPd], mean pulmonary arterial pressure [mPAP], and transpulmonary gradient [TPG]) was evaluated at rest from Baseline to Week 24. The median change in hemodynamic parameters from Baseline to Week 24 via right-heart catheterization (RHC) is presented.
Measured: 24 weeks
Change in Heart Rate at Rest From Baseline to Week 24
The change in heart rate was evaluated at rest from Baseline to Week 24.
Measured: 24 weeks
Change in Cardiac Output at Rest From Baseline to Week 24
The change in cardiac output was evaluated at rest from Baseline to Week 24. The median change in cardiac output from Baseline to Week 24 is presented.
Measured: 24 weeks
Change in Arterial and Venous Oxygen Saturation at Rest From Baseline to Week 24
The change in arterial and venous oxygen saturation was evaluated at rest from Baseline to Week 24.
Measured: 24 weeks
Change in Pulmonary Vascular Resistance (PVR) at Rest From Baseline to Week 24
The change in pulmonary vascular resistance (PVR) was evaluated at rest from Baseline to Week 24.
Measured: 24 weeks
Change in 6-minute Walk Distance (6MWD) From Baseline to Weeks 12 and 24.
The 6-Minute Walk Test was conducted at Screening, Baseline prior to starting study drug and at least 24 hours after the Screening test, and during the Treatment Phase at Weeks 12 and 24.
Measured: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Atrium and Right Ventricle Area) From Baseline to Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Measured: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricle Diameter) From Baseline to Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Measured: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricular Systolic Pressure) From Baseline to Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Measured: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion) From Baseline to Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Measured: Baseline and Weeks 12 and 24
Change in Quality of Life From Baseline to Weeks 12 and 24
The 36-item Short Form Survey (SF-36) is a health related quality of life instrument, which measures dimensions of physical and social roles and functioning, mental health, vitality, and pain. Items are scored on a 0 to 100 range so that the lowest scores represent the highest disability. The quality of life assessment was conducted at Baseline and Weeks 12 and 24 and the change from Baseline to Weeks 12 and 24 is presented.
Measured: Baseline and Weeks 12 and 24
Change in Plasma Brain N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Weeks 12 and 24
NT-proBNP was assessed at Baseline, Weeks 12 and 24.
Measured: Baseline to Weeks 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2009 (estimated)
- Study startJan 2011
- Primary completionApr 2013
- Study completionApr 2013
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 Portopulmonary HypertensionStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of California, Los Angeles, Brigham and Women's Hospital, University of Texas, Emory University
- Responsible party
- Sponsor
- Investigators
- Rajan Saggar, MD, Study director, University of California, Los AngelesMicah Fisher, MD, Study director, Emory UniversityAaron Waxman, MD, PhD, Study director, Brigham and Women's HospitalSonja Bartolome, MD, Study director, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01028651
- Sponsor's protocol ID
- RIV-PH-414
- Status last verified
- Jan 2017
- First submitted
- 8 Dec 2009
- Last updated
- 24 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
- ClinicalTrials.gov ID
- NCT01028651
- Acronym / sponsor ID
- RIV-PH-414
- Keywords
- PAH, Pulmonary Hypertension, Remodulin, Treprostinil, Quality of Life
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- University of California, Los Angeles, Brigham and Women's Hospital, University of Texas, Emory University
- Study start
- Jan 2011
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 9 Dec 2009 (estimated)
- Results
- Posted 24 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a multicenter, prospective, observational, open-label study. Patients meeting inclusion/exclusion criteria received treatment with treprostinil as recommended by their treating physicians and were followed according to standard of care. This observational study collected clinical data and biologic specimens from patients who were treated for portopulmonary hypertension (PoPH), with a goal of achieving hemodynamic parameters appropriate for orthotopic liver transplantation candidacy, including mean pulmonary arterial pressure (mPAP) less than 35 mmHg and pulmonary vascular resistance (PVR) less than 3 Wood-units (WU) at Week 24 in patients with severe PoPH.
Detailed description
Treprostinil is approved as a continuous subcutaneous (SC) or intravenous (IV) infusion by the FDA for the treatment of WHO group I PAH with New York Heart Association (NYHA) Functional Class II, III or IV symptomatology. To date, treprostinil has not been studied in the setting of PoPH; however, it is commonly prescribed in this setting. This was an observational, open-label, multicenter study which documented the safety and efficacy profile of this agent in PoPH to facilitate orthotopic liver transplantation (OLT).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Portopulmonary hypertension | – | Drug: Treprostinil |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.
Key inclusion criteria (7 listed)
- Patients must:
Key exclusion criteria (4 listed)
- Patients must not:
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: RemodulinRemodulin is supplied in concentrations of 1, 2.5 , 5, and 10 mg/mL and can be administered as supplied or diluted for intravenous (IV) infusion prior to administration. Remodulin is indicated for subcutaneous (SC) or IV use only as a continuous infusion. Remodulin is preferably infused subcutaneously, but can be administered by a central IV line if the SC route is not tolerated. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min. | Drug | Portopulmonary hypertension |
Primary outcome
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.
Time frame: 24 Weeks
The primary efficacy endpoint was the number of subjects who achieved a mean pulmonary arterial pressure (mPAP) less than 35 mmHg and a pulmonary vascular resistance (PVR) less than 3 Wood units (WU) at Week 24 in patients with severe portopulmonary hypertension (PoPH).
12 secondary outcomes
Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24
Time frame: 24 weeks
Change in Heart Rate at Rest From Baseline to Week 24
Time frame: 24 weeks
Change in Cardiac Output at Rest From Baseline to Week 24
Time frame: 24 weeks
Change in Arterial and Venous Oxygen Saturation at Rest From Baseline to Week 24
Time frame: 24 weeks
Change in Pulmonary Vascular Resistance (PVR) at Rest From Baseline to Week 24
Time frame: 24 weeks
Change in 6-minute Walk Distance (6MWD) From Baseline to Weeks 12 and 24.
Time frame: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Atrium and Right Ventricle Area) From Baseline to Weeks 12 and 24
Time frame: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricle Diameter) From Baseline to Weeks 12 and 24
Time frame: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricular Systolic Pressure) From Baseline to Weeks 12 and 24
Time frame: Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion) From Baseline to Weeks 12 and 24
Time frame: Baseline and Weeks 12 and 24
Change in Quality of Life From Baseline to Weeks 12 and 24
Time frame: Baseline and Weeks 12 and 24
Change in Plasma Brain N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Weeks 12 and 24
Time frame: Baseline to Weeks 12 and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Portopulmonary Hypertension
Not yet recruitingObservational study
Heart Problems in Children With Chronic Liver Disease
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Not yet recruitingObservational study
Genetic Hallmarks of Patients With Congenital Portosystemic Shunts and Portopulmonary Hypertension
Portopulmonary Hypertension, Pulmonary Arterial Hypertension (PAH)
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.
Rajan Saggar, MD study director
University of California, Los Angeles
Micah Fisher, MD study director
Emory University
Aaron Waxman, MD, PhD study director
Brigham and Women's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Portopulmonary Hypertension and Pulmonary Arterial Hypertension, run by United Therapeutics at 4 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 7 inclusion and 4 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 24 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Feb 2017). 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?
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24. (time frame: 24 Weeks). 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 24 Feb 2017.