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 Wisconsin, Madison
University of Texas
University of Kansas
Emory University
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01028651
First received: December 8, 2009
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

This is a multicenter, observational, open-label study. Patients meeting inclusion/exclusion criteria will receive treatment with treprostinil as recommended by their treating physician and will follow patients according to standard of care. This observational study proposes to collect clinical data and biologic specimens from patients who will be treated for Portopulmonary Hypertension, with a goal of achieving hemodynamic parameters acceptable for liver transplantation.


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

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Phase 4 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:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: November 2009
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 sodium

Remodulin is supplied in 20 mL vials in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL. Remodulin can be administered as supplied or diluted for intravenous infusion with Sterile Water for Injection, 0.9% Sodium Chloride Injection, or Flolan® Sterile Diluent for Injection prior to administration.

Remodulin is indicated for subcutaneous (SC) or intravenous (IV) use only as a continuous infusion. Remodulin is preferably infused subcutaneously, but can be administered by a central intravenous line if the subcutaneous route is not tolerated, because of severe site pain or reaction. 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:

Portopulmonary hypertension (PoPH) is characterized by the presence of pulmonary arterial hypertension (PAH) in the setting of portal hypertension, and is considered the third most common cause of PAH[[1], [2]]. Approximately 2 to 6% of patients with portal hypertension demonstrate significant pulmonary hypertension based on hemodynamic observation[[3], [4], [5]]. In those patients undergoing liver transplant evaluation, the prevalence of PAH is approximately 5-6%[[4], [6], [7]]. PoPH is associated with a median survival ranging from 8 months to 2.3 years.

Among patients undergoing liver transplantation, the presence of PoPH contributes significantly to morbidity and mortality[[8], [9], [10]]. In particular, patients with PoPH who undergo OLT with mean pulmonary artery pressure (PAPm) > 35 mmHg and/or pulmonary vascular resistance (PVR) > 250 dyn/s/cm5 have > 90% risk of death posttransplant[[8]]. As such, in many transplant centers, the presence of severe PoPH ((PAPm) > 35 mmHg and/or pulmonary vascular resistance (PVR) > 250 dyn/s/cm5) is considered an absolute contraindication to OLT[[6], [11], [12]]. These patients thus have limited treatment options.

To date, pulmonary vasodilator medication use in the setting of PoPH has largely been limited to single case reports or small case series. These include intravenous (IV)/inhaled prostacyclin, sildenafil and bosentan [[15], [16], [17], [18], [19], [20], [21]]. More recently, encouraging results have been published in open label studies with the use of IV epoprostenol which was shown to improve pulmonary hemodynamics and possibly survival [[19], [21], [22]]. Specifically, in patients with severe PoPH who were referred for OLT, initiation of IV epoprostenol allowed for mPA < 35 mmHg in certain cases, allowing a successful bridge to OLT [[21], [22]].

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) Class II, III or IV symptomatology[[13], [14]]. To date, treprostinil has not been studied in the setting of PoPH; however, it is commonly prescribed in this setting. This is an observational, open-label, multi-center study will attempt to document the safety and efficacy profile of this agent in PoPH to facilitate OLT efficacy profile of this agent in PoPH to facilitate OLT.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Subjects will be recruited from four Pulmonary Hypertension Centers in the US, referred for portopulmonary hypertension.

Criteria

Inclusion Criteria:

  • Patients must:

    1. Confirmed severe PoPH documented on standard of care right-heart catheterization (RHC) with a plan to initiate treprostinil therapy, as recommended by the treating physician state within 30 days.
    2. Have portal hypertension.
    3. Be otherwise suitable candidates for OLT.
    4. Treprostinil therapy must be recommended by the treating physician per standard of care.
    5. Be NYHA Class II, III, or IV
    6. Have Pulmonary Capillary Wedge Pressure (PCW) < 18 mmHg AND transpulmonary gradient (TPG) ≥ 15 mmHg Severe PAH is defined as a resting mean pulmonary artery pressure (mPA) > 25 mmHg AND pulmonary vascular resistance (PVR) ≥ 3 wood-units by right-heart catheterization (RHC) performed as part of standard of care evaluation within 30 days of enrollment

Exclusion Criteria:

  • Patients must not:

    1. Be taking any investigational therapy as part of a clinical trial for any indication within 30 days of enrollment.
    2. Be receiving any vasodilator treatment for pulmonary hypertension (i.e. bosentan, sitaxsentan, ambrisentan, sildenafil, tadalafil, epoprostenol, beraprost, iloprost, inhaled treprostinil) at the time of enrollment.
    3. Exhibit 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
UCLA
Los Angeles, California, United States, 90024
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
United Therapeutics
University of California, Los Angeles
Brigham and Women's Hospital
University of Wisconsin, Madison
University of Texas
University of Kansas
Emory University
Investigators
Study Director: Rajan Saggar, MD University of California, Los Angeles
Study Director: Michael Krowka, MD Mayo Clinic
Study Director: Aaron Waxman, MD, PhD Brigham and Women's Hospital
Study Director: James Runo, MD University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01028651     History of Changes
Other Study ID Numbers: RIV-PH-414
Study First Received: December 8, 2009
Last Updated: June 25, 2014
Health Authority: United States: Institutional Review Board

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

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases
Treprostinil
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014