Ambrisentan for the Improvement in Right Ventricular Strain in Scleroderma Associated Pulmonary Arterial Hypertension (AMERICA-PAH)

This research study is looking at the use of the drug ambrisentan and if it can improve right ventricle function in people with systemic sclerosis-associated pre-pulmonary arterial hypertension. It is also looking at using right ventricle function changes as a marker of disease severity.

Study Overview

• Status: Terminated
• Conditions: Pre-Pulmonary Atrial Hypertension
• Intervention / Treatment: Drug: Ambrisentan

Detailed Description

This research study is looking at the use of the drug ambrisentan and if it can improve right ventricle function in people with systemic sclerosis-associated pre-pulmonary arterial hypertension. It is also looking at using right ventricle function changes as a marker of disease severity.

Pre-pulmonary arterial hypertension is a borderline elevation in blood pressure in the lungs. Pre-pulmonary arterial hypertension is not currently treated with the drug therapies that are used for pulmonary arterial hypertension. It represents a group of patients that are at risk for developing pulmonary arterial hypertension.

The administration of ambrisentan is the experimental part of this study. Ambrisentan has not been approved by the FDA for use of improving right ventricle function in people with pre-pulmonary arterial hypertension. You will still receive your normal clinical care.

The purpose of this study is to learn more about ambrisentan and its role in treating systemic sclerosis-associated pre-pulmonary arterial hypertension. Ambrisentan is already approved for use in people with systemic sclerosis-associated pulmonary arterial hypertension, but this study wants to research its role in people with pre-pulmonary arterial hypertension.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >18 years, < 80 years

• Systemic sclerosis with any of the following features:

  1. Duration of Raynaud's phenomena >8 years
  2. Anticentromere antibody positivity
  3. isolated nucleolar-pattern ANA positivity
  4. Extensive telangiectasias
  5. DLCO < 60% in the absence of extensive ILD
  6. FVC%/DLCO% >1.6
  7. Unexplained dyspnea
• Right heart catheterization-proven pre PAH (mean PAP 20-25 mmHg and pulmonary capillary wedge pressure <15 mmHg)
• Systolic blood pressure >100 mmHg
• Reliable contraception for women of childbearing age
• Informed consent

Exclusion Criteria:

• < 18 years or > 80 years
• Left ventricular ejection fraction < 55%
• Systolic or diastolic left ventricular congestive heart failure
• Liver disease (abnormal AST/ALT, chronic hepatitis, or cirrhosis)
• Extensive ILD or FVC< 60%
• Pregnant
• Breast-feeding women
• Cyclosporine use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ambrisentan; Subjects will be randomly assigned in a 1:1 ration according to the computer generated random numbers to receive either placebo (sugar pill) or ambrisentan.	Drug: Ambrisentan; Subjects will be randomized 1:1 ratio according to computer generated random numbers to receive either "placebo" or ambrisentan 5mg daily for one month followed by 10 mg daily for the 5 months in a double-blinded manner.; Other Names: Letairis
Placebo Comparator: Placebo; Subjects will be randomly assigned in a 1:1 ration according to the computer generated random numbers to receive either placebo (sugar pill) or ambrisentan.	Drug: Ambrisentan; Subjects will be randomized 1:1 ratio according to computer generated random numbers to receive either "placebo" or ambrisentan 5mg daily for one month followed by 10 mg daily for the 5 months in a double-blinded manner.; Other Names: Letairis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in right ventricular (RV) myocardio strain > 2%	Assess for tolerance, gas exchange, and therapeutic benefit, resting oximetry, six minute walk with oximetry, pulmonary function testing with diffusion capacity (DLCO), and functional class will be assessed prior to ambrisentan initiation, and 1,3, and 6 months.	1, 3 and 6 months

Collaborators and Investigators

• Sponsor: National Jewish Health
• Investigators: Principal Investigator: Brett Fenster, MD, National Jewish Health

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): May 25, 2017
• Study Completion (Actual): May 25, 2017

Study Registration Dates

• First Submitted: May 6, 2014
• First Submitted That Met QC Criteria: June 19, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pre-Pulmonary Atrial Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: HS-2716