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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 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

December 8, 2009
June 25, 2014
November 2009
April 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01028651 on ClinicalTrials.gov Archive Site
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 ]
Same as current
Not Provided
Not Provided
 
A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension
Phase 4 Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension

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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Not Provided
Probability Sample

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

  • Portopulmonary Hypertension
  • Pulmonary Arterial Hypertension
  • Pulmonary 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
Portopulmonary hypertension
Intervention: Drug: Treprostinil sodium
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. 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.
Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01028651
RIV-PH-414
No
United Therapeutics
United Therapeutics
  • University of California, Los Angeles
  • Brigham and Women's Hospital
  • University of Wisconsin, Madison
  • University of Texas
  • University of Kansas
  • Emory University
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
United Therapeutics
June 2014

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