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Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial (Portopulm)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT01224210
First received: October 18, 2010
Last updated: May 20, 2016
Last verified: May 2016
History of Changes
  Purpose

This is an Open Label, Multicenter, pilot clinical trial to assess the efficacy and safety of an oral selective Endothelin Receptor Antagonist (ambrisentan) in patients with portopulmonary hypertension.

Preliminary evidence suggests that ambrisentan is safe and effective in patients with portopulmonary hypertension. The goal of therapy for these patients is to improve symptoms of dyspnea and to improve pulmonary hemodynamics to a mean pulmonary artery pressure <35 mm Hg in order to make patients eligible for liver transplantation. Therefore, the primary endpoints for this study will include 6 minute walk distance (6MWD) and pulmonary vascular resistance (PVR).

Eligible subjects will receive 5 mg ambrisentan once-daily for the first 4 weeks. After the initial 4-week period, investigators will increase study drug dose to 10 mg once daily (both 5 mg and 10 mg doses are FDA approved). If 10 mg is not tolerated in the opinion of investigator, then the investigator may decrease the dose back to 5 mg once daily. Primary outcome is a change in both the 6MWD and in PVR from baseline to Week 24. Subjects will be monitored with liver function tests (LFT) every 2 weeks for the first 8 weeks, then every 4 weeks thereafter. These safety laboratory tests may be performed at a local phlebotomy laboratory or at the Investigator clinic. In addition, the Investigator will assess each subject for safety and efficacy at Week 4, Week 12, and Week 24. Following Week 24, subjects will be assessed for safety and efficacy every 12 weeks. Patients will be followed for a total of 1 year. After 1 year, if the Investigator feels that continuing the treatment will be beneficial to the patients, they will be provided with ambrisentan by Gilead Pharmaceuticals, free of charge.


Condition Intervention
Portopulmonary Hypertension
 Drug: Ambrisentan

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial

Resource links provided by NLM:

Drug Information available for: Ambrisentan
U.S. FDA Resources

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Change in PVR [ Time Frame: from baseline to Week 24 ] [ Designated as safety issue: No ]
    Change in PVR from baseline to Week 24 for all patients (using cardiac output [CO] measured by the thermodilution method and reported as percent difference from baseline).


Secondary Outcome Measures:
  • 6 Minute Walk Distance [ Time Frame: Change from baseline to Week 24 ] [ Designated as safety issue: No ]
    Change from baseline in 6MWD at Week 24 for all patients. (difference measured in meters).
Enrollment: 30
Study Start Date: March 2010
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Ambrisentan
Open Label Ambrisentan
 Drug: Ambrisentan
Ambrisentan once-daily in the morning with or without food. The adult dose selected for this study will be 5 mg for the first 4 weeks. After the initial 4 weeks the dose will be increased to 10mg (available doses are 5, and 10 mg) based on tolerance safety. Subjects will remain on 10mg until they complete the study. Dose adjustments may be made based on side effects.
Other Name: Letairis

  Eligibility
Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects need to fulfill all of the following 4 criteria:

  1. Evidence of portal hypertension (by hemodynamic measurement, or by Doppler flow of portal circulation, or by clinical evidence of portal hypertension such as esophageal or gastric varices, as evidenced by prior upper endoscopy).

  2. Evidence of pulmonary arterial hypertension by right heart catheterization (all three criteria need to be present) Right heart catheterization may have been performed up to 30 days prior to screening

    • Mean PAP (pulmonary artery pressure) >25 mm Hg, and
    • PVR (pulmonary vascular resistance) >240 dynes/s/cm5, and
    • TPG (transpulmonary gradient = meanPAP -PAWP) >12 mm Hg
  3. Baseline AST, ALT < 5 times the upper limit of normal, total Bili < 3.0 mg/dl, and mild liver impairment with Child -Pugh class A or B
  4. Ages 18 years and above

Exclusion Criteria:

  1. Presence of any other etiology of pulmonary arterial hypertension (HIV, connective tissue disease, sickle cell, left heart failure, chronic thromboembolic PH, etc)
  2. Treatment with prostacyclins, other ERAs, or PDE5 inhibitors within 30 days of enrollment.
  3. Moribund state or anticipated death within 1 month.
  4. AST or ALT ≥ 5 times upper limit of normal
  5. Total bilirubin ≥ 3.0 mg/dl
  6. Significant lung disease (obstructive lung disease with FEV1 < 1L, or FEV1/FVC <50%; or restrictive lung disease with Total Lung Capacity < 60% predicted). PFTs may have been performed up to 6 months prior to enrollment.
  7. Pregnancy
  8. Age <18 years
  9. Child -Pugh class C
  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: NCT01224210

Locations
United States, California
UCSD Medical Center
La Jolla, California, United States, 92093
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
The Ohio State University Medical Center
Columbus, Ohio, United States, 43221
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Tufts Medical Center
Gilead Sciences
Investigators
Principal Investigator: Ioana Preston, MD Tufts Medical Center
  More Information

Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT01224210     History of Changes
Other Study ID Numbers: Ambrisentan Portopulm Study 
Study First Received: October 18, 2010
Last Updated: May 20, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Tufts Medical Center:
portopulmonary hypertension
portal hypertension
esophageal or gastric varices
right heart catheterization
transpulmonary gradient
 Endothelin Receptor Antagonist
Ambrisentan
Letairis
pulmonary hemodynamics

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
 Lung Diseases
Respiratory Tract Diseases
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016