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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT01224210
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	N/A
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Tufts Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Ioana Preston, MD
Principal Investigator Affiliation	Tufts Medical Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other, Industry
Overall Status	Active, not recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Portopulmonary Hypertension

Arms & Interventions

Arms

Other: Ambrisentan

Open Label Ambrisentan

Interventions

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UCSD Medical Center, La Jolla, California

Status

Address

UCSD Medical Center

La Jolla, California, 92093

Mayo Clinic Florida, Jacksonville, Florida

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Address

Mayo Clinic Florida

Jacksonville, Florida, 32224

Tufts Medical Center, Boston, Massachusetts

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Address

Tufts Medical Center

Boston, Massachusetts, 02111

University of North Carolina, Chapel Hill, North Carolina

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Address

University of North Carolina

Chapel Hill, North Carolina, 27599

The Ohio State University Medical Center, Columbus, Ohio

Status

Address

The Ohio State University Medical Center

Columbus, Ohio, 43221

UT Southwestern Medical Center, Dallas, Texas

Status

Address

UT Southwestern Medical Center

Dallas, Texas, 75390

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