Clinical trial NCT01028651: A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
Official title: An Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Portopulmonary Hypertension
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Keywords: PAH
Pulmonary Hypertension
Remodulin
Treprostinil
Quality of Life
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: University of California, Los Angeles
name: Brigham and Women's Hospital
name: University of Texas
name: Emory University
First posted: 2009-12-09
Enrollment: 13
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.

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).

Eligibility 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.

Primary outcomes:
measure: Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.
timeFrame: 24 Weeks
Secondary outcomes:
measure: Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24
timeFrame: 24 weeks
measure: Change in Heart Rate at Rest From Baseline to Week 24
timeFrame: 24 weeks
measure: Change in Cardiac Output at Rest From Baseline to Week 24
timeFrame: 24 weeks
measure: Change in Arterial and Venous Oxygen Saturation at Rest From Baseline to Week 24
timeFrame: 24 weeks
measure: Change in Pulmonary Vascular Resistance (PVR) at Rest From Baseline to Week 24
timeFrame: 24 weeks
measure: Change in 6-minute Walk Distance (6MWD) From Baseline to Weeks 12 and 24.
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Echocardiogram Parameters (Right Atrium and Right Ventricle Area) From Baseline to Weeks 12 and 24
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Echocardiogram Parameters (Right Ventricle Diameter) From Baseline to Weeks 12 and 24
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Echocardiogram Parameters (Right Ventricular Systolic Pressure) From Baseline to Weeks 12 and 24
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion) From Baseline to Weeks 12 and 24
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Quality of Life From Baseline to Weeks 12 and 24
timeFrame: Baseline and Weeks 12 and 24
measure: Change in Plasma Brain N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Weeks 12 and 24
timeFrame: Baseline to Weeks 12 and 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Atlanta
country: United States
facility: Emory Univeristy
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of California, Los Angeles
name: Rajan Saggar, MD
role: STUDY_DIRECTOR
affiliation: Emory University
name: Micah Fisher, MD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital
name: Aaron Waxman, MD, PhD
role: STUDY_DIRECTOR
affiliation: UT Southwestern Medical Center
name: Sonja Bartolome, MD
role: STUDY_DIRECTOR
References: