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Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial (Portopulm)
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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: | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial |
- Change in PVR [ Time Frame: from baseline to Week 24 ]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).
- 6 Minute Walk Distance [ Time Frame: Change from baseline to Week 24 ]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: | September 2017 |
| 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) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Subjects need to fulfill all of the following 4 criteria:
- 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).
-
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
- 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
- Ages 18 years and above
Exclusion Criteria:
- Presence of any other etiology of pulmonary arterial hypertension (HIV, connective tissue disease, sickle cell, left heart failure, chronic thromboembolic PH, etc)
- Treatment with prostacyclins, other ERAs, or PDE5 inhibitors within 30 days of enrollment.
- Moribund state or anticipated death within 1 month.
- AST or ALT ≥ 5 times upper limit of normal
- Total bilirubin ≥ 3.0 mg/dl
- 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.
- Pregnancy
- Age <18 years
- Child -Pugh class C
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01224210
| 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 | |
| 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: | December 20, 2016 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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 August 18, 2017