Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan

NCT01051960 | Completed Phase 4 Results

• 1 other identifier: 10-000567
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the clinical characteristics and hemodynamic profiles that predict exercise induced pulmonary hypertension in 15 patients with systemic sclerosis. The study also aims to determine the effectiveness of Ambrisentan for subjects with exercise induced Pulmonary Arterial Hypertension (PAH) with scleroderma

Conditions

Systemic Sclerosis; Shortness of Breath; Pulmonary Hypertension

Keywords

Systemic Sclerosis; connective tissue disease; Shortness of breath; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in Exercise Pulmonary Hemodynamics From Baseline to Week 24

  We defined ePH (exercise PH) as an mPAP of 30 mmHg, PCWP of 18 mm Hg, and a transpulmonary gradient (TPG) of 15 mm Hg, where TPG equals mPAP minus PCWP. We defined ePVH (exercise pulmonary venous hypertension) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg. We defined eoPH (exercise out of proportion) as an mPAP of 30 mm Hg, PCWP of 18 mm Hg, and a TPG of 15 mm Hg (4). Our hypothesis was that SSc patients with normal exercise physiology and ePVH have a different patho-physiology compared to patients with pulmonary vascular disease (ePH and eoPH).

  24 weeks

Secondary Outcomes (4)

• Change in Distance Walked in Six Minutes From Baseline to 24 Week

  24 weeks

• Quality of Life (QOL) Based on SF36 and HAQ-DI

  24 weeks

• HAQ-DI (Health Assessment Questionnaire Disability Index)

  24 weeks

• St. George's Respiratory Questionnaire

  24 weeks

Study Arms (1)

ambrisentan

EXPERIMENTAL

ambrisentan dosed at either 5mg or 10mg orally once per day

Drug: Ambrisentan

Interventions

Ambrisentan DRUG

Ambrisentan 5mg or 10mg once daily

Also known as: Letairis

ambrisentan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Systemic Sclerosis diagnosed by the American College of Rheumatology consensus statement including any of the following:
• Limited
• Diffuse
• Sine Scleroderma
• Patients must be willing and able to undergo right heart catheterization with lower extremity cycle ergometry
• Mean pulmonary artery pressure (mPAP) \> 30mmHg with exercise; PCWP ≤ 15mmHg on RHC at rest
• Men and women, ages 18 years of age or older
• Standard adjunctive medications will be allowed concurrently in this study at the discretion of the treating pulmonologist and rheumatologist, including digoxin, diuretics, anticoagulants (e.g. warfarin), stable immunosuppression or other anti-fibrotic therapy for at least one month prior to enrollment

You may not qualify if:

• Resting PAH (mPAP \> 25mmHg) on right heart catheterization
• Other known causes of PAH including prior venous thromboembolism, HIV infection, chronic liver disease with portal hypertension, left ventricular systolic dysfunction (e.g. LVEF \< 40%), and congenital causes of PAH
• Severe hepatic disease precluding the use of ambrisentan (AST/ALT ≥3x ULN).
• Women who are pregnant or breastfeeding.
• Concurrent therapy with a prostanoid or prostanoid analogue, PDE5 inhibitors, or enrolled in another active clinical study.
• Use of any prostacyclin or endothelial receptor antagonist (ERA) within 30 days before study entry.
• Bed or wheel chair bound or a baseline 6-Minute Walk distance (6MWD) less than 150 meters.
• Childbearing capable women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
• New York Heart Association (NYHA) Classification: Class IV
• Renal dysfunction (serum creatinine \>2.5mg/dL).
• Uncontrolled sleep apnea.

Sponsors & Collaborators

• University of California, Los Angeles: lead
• Gilead Sciences: collaborator

Study Sites (1)

David Geffen School of Medicine, University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Saggar R, Khanna D, Shapiro S, Furst DE, Maranian P, Clements P, Abtin F, Dua S, Belperio J, Saggar R. Brief report: effect of ambrisentan treatment on exercise-induced pulmonary hypertension in systemic sclerosis: a prospective single-center, open-label pilot study. Arthritis Rheum. 2012 Dec;64(12):4072-7. doi: 10.1002/art.34614.

  PMID: 22777623 RESULT

MeSH Terms

Conditions

Scleroderma, Systemic; Dyspnea; Hypertension, Pulmonary; Connective Tissue Diseases

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Skin and Connective Tissue Diseases; Skin Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Rajan Saggar, MD
• Organization: University of California, Los Angeles

rsaggar@mednet.ucla.edu

(310) 794-9718

Study Officials

• Rajeev Saggar, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Dinesh Khanna, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: January 20, 2010
• Study Start: March 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: January 1, 2011
• Last Updated: November 2, 2020
• Results First Posted: November 2, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)