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

Completed

• Conditions: Pulmonary Hypertension; Pulmonary Arterial Hypertension; Portopulmonary Hypertension
• Interventions: Drug: Treprostinil

• Registration Number: NCT01028651
• Lead Sponsor: United Therapeutics

Brief 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. 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 Timeline

• Study First Submitted: 2009-12-08
• Study First Submitted QC: 2009-12-08
• Study First Posted: 2009-12-09
• Study Start: 2011-01
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Results First Submitted: 2016-09-14
• Status Verified: 2017-01
• Results First Submitted QC: 2017-01-05
• Last Update Submitted: 2017-01-05
• Results First Posted: 2017-02-24
• Last Update Posted: 2017-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Portopulmonary hypertension	Treprostinil	-

Primary Outcome Measures

Name	Time	Method
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.	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

Name	Time	Method
Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24	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	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	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	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	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.	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	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	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	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	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	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	Baseline to Weeks 12 and 24	NT-proBNP was assessed at Baseline, Weeks 12 and 24.

Trial Locations

Locations (4)

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Emory Univeristy; 🇺🇸 Atlanta, Georgia, United States

University of Texas, Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States