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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

December 8, 2009
January 5, 2017
January 2011
April 2013   (Final data collection date for primary outcome measure)
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).
To estimate the probability of achieving a mPAP to less than 35 mmHg and a PVR less than 3 Wood-units in subjects with severe portopulmonary hypertension undergoing OLT treated for 24 weeks with treprostinil. [ Time Frame: 24 Weeks ]
Complete list of historical versions of study NCT01028651 on ClinicalTrials.gov Archive Site
  • 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.
To assess the effect of treprostinil therapy on safety, secondary efficacy endpoints and chemokine profiles. [ Time Frame: 24 weeks, and 30 day post-OLT and one year post-OLT ]
Not Provided
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A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
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.
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).
Observational
Observational Model: Cohort
Time Perspective: Prospective
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Probability Sample
Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.
  • Portopulmonary Hypertension
  • Pulmonary Arterial Hypertension
  • Pulmonary 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
Portopulmonary hypertension
Intervention: Drug: Treprostinil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
13
April 2013
April 2013   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
Child, Adult, Senior
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01028651
RIV-PH-414
No
Not Provided
Not Provided
Not Provided
United Therapeutics
United Therapeutics
  • University of California, Los Angeles
  • Brigham and Women's Hospital
  • University of Texas
  • Emory University
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
United Therapeutics
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP