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A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension

This study has been completed.
Sponsor:
Collaborators:
University of California, Los Angeles
Brigham and Women's Hospital
University of Texas
Emory University
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01028651
First received: December 8, 2009
Last updated: January 5, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention
Portopulmonary Hypertension
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Drug: Treprostinil

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by United Therapeutics:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24 [ Time Frame: 24 weeks ]
    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.

  • Change in Heart Rate at Rest From Baseline to Week 24 [ Time Frame: 24 weeks ]
    The change in heart rate was evaluated at rest from Baseline to Week 24.

  • Change in Cardiac Output at Rest From Baseline to Week 24 [ Time Frame: 24 weeks ]
    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.

  • Change in Arterial and Venous Oxygen Saturation at Rest From Baseline to Week 24 [ Time Frame: 24 weeks ]
    The change in arterial and venous oxygen saturation was evaluated at rest from Baseline to Week 24.

  • Change in Pulmonary Vascular Resistance (PVR) at Rest From Baseline to Week 24 [ Time Frame: 24 weeks ]
    The change in pulmonary vascular resistance (PVR) was evaluated at rest from Baseline to Week 24.

  • Change in 6-minute Walk Distance (6MWD) From Baseline to Weeks 12 and 24. [ Time Frame: Baseline and 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.

  • 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 ]
    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.

  • Change in Echocardiogram Parameters (Right Ventricle Diameter) From Baseline to Weeks 12 and 24 [ Time Frame: Baseline and 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.

  • Change in Echocardiogram Parameters (Right Ventricular Systolic Pressure) From Baseline to Weeks 12 and 24 [ Time Frame: Baseline and 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.

  • Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion) From Baseline to Weeks 12 and 24 [ Time Frame: Baseline and 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.

  • Change in Quality of Life From Baseline to Weeks 12 and 24 [ Time Frame: Baseline and 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.

  • 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 ]
    NT-proBNP was assessed at Baseline, Weeks 12 and 24.


Enrollment: 13
Study Start Date: January 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Portopulmonary hypertension Drug: Treprostinil

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.

Other Name: Remodulin

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).
  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.
Criteria

Inclusion Criteria:

  • Patients must:

    1. Had portal hypertension.
    2. Be otherwise suitable candidates for OLT.
    3. 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.
    4. Treprostinil therapy must be recommended by the treating physician per standard of care.
    5. Be NYHA Functional Class II, III, or IV.
    6. Had pulmonary capillary wedge (PCW) pressure ≤18 mmHg and transpulmonary gradient (TPG) ≥15 mmHg.

Exclusion Criteria:

  • Patients must not:

    1. Had received any any investigational therapy as part of a clinical trial for any indication within 30 days prior to enrollment.
    2. 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.
    3. Had renal failure requiring hemodialysis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01028651

Locations
United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90024
United States, Georgia
Emory Univeristy
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Texas
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75235
Sponsors and Collaborators
United Therapeutics
University of California, Los Angeles
Brigham and Women's Hospital
University of Texas
Emory University
Investigators
Study Director: Rajan Saggar, MD University of California, Los Angeles
Study Director: Micah Fisher, MD Emory University
Study Director: Aaron Waxman, MD, PhD Brigham and Women's Hospital
Study Director: Sonja Bartolome, MD UT Southwestern Medical Center
  More Information

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01028651     History of Changes
Other Study ID Numbers: RIV-PH-414
Study First Received: December 8, 2009
Results First Received: September 14, 2016
Last Updated: January 5, 2017

Keywords provided by United Therapeutics:
PAH
Pulmonary Hypertension
Remodulin
Treprostinil
Quality of Life

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Treprostinil
Antihypertensive Agents

ClinicalTrials.gov processed this record on April 21, 2017