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.