Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
Information source: Tufts Medical Center
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Portopulmonary Hypertension
Intervention: Ambrisentan (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Tufts Medical Center Official(s) and/or principal investigator(s):
Ioana Preston, MD, Principal Investigator, Affiliation: Tufts Medical Center
Overall contact:
Karen Visnaw, RN, BS, ADN, Phone: 617-636-1334, Email: Kvisnaw@Tuftsmedicalcenter.org
Summary
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.
Clinical Details
Official title: Ambrisentan in Patients With Porto-pulmonary Hypertension A Multicenter Open Label Trial
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in PVR
Secondary outcome: 6 Minute Walk Distance
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Karen Visnaw, RN, BS, ADN, Phone: 617-636-1334, Email: Kvisnaw@Tuftsmedicalcenter.org
Mayo Clinic, Phoenix, Arizona 85054, United States; Not yet recruiting
Arcenio Galindo, RRT, B.A, Phone: 480-342-3987, Email: Galindo.arcenio@mayo.edu
Robert L. Scott, MD, Principal Investigator
UCSD Medical Center, La Jolla, California 92093, United States; Not yet recruiting
Melissa Thrasher, BS, CCRC, Phone: 858-657-7127, Email: mthrasher@ucsd.edu
David S. Poch, MD, Principal Investigator
Mayo Clinic Florida, Jacksonville, Florida 32224, United States; Recruiting
Pam Long, RN, Phone: 904-953-2255, Email: Long.pamela@mayo.edu
Charles D Burger, M.D, Principal Investigator
Tufts Medical Center, Boston, Massachusetts 02111, United States; Recruiting
Karen Visnaw, RN, BS, ADN, Phone: 617-636-1334, Email: Kvisnaw@Tuftsmedicalcenter.org
Ioana Preston, MD, Principal Investigator
Mayo Clinic Minnesota, Rochester, Minnesota 55905, United States; Recruiting
Annette McNallan Annette McNallan, RN, Phone: 507-266-3639, Email: Mcnallan.Annette@mayo.edu
LuAnne J Koenig, RN, AAN RN, Phone: 507-284-4298, Email: koenig.luanne@mayo.edu
Karen Swanson, MD, Principal Investigator
Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Dorothy Williams, LVN II, Phone: 713-798-2560, Email: dorothyw@bcm.edu
Zeenat Safdar, MD, Principal Investigator
Additional Information
Starting date: March 2010
Last updated: November 28, 2012
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