Early Therapy of Pulmonary Arterial Hypertension

Exercise-induced increase of the pulmonary arterial pressure may be an early sign of pulmonary arterial hypertension. It has been shown that patients with normal pulmonary arterial pressure at rest but elevated pulmonary arterial pressure during exercise have a decreased exercise-capacity and may have a worse prognosis compared to patients with normal pulmonary arterial pressure values at rest and during exercise. According to the currently used definition pulmonary hypertension can be diagnosed if the mean pulmonary arterial pressure is higher than 25mmHg at rest or 30mmHg during exercise. In this study patients with a risk for pulmonary arterial hypertension (connective tissue disease) and increased pulmonary arterial pressure values during exercise are receiving a therapy with a dual endothelin receptor antagonist - bosentan, a therapy established for pulmonary arterial hypertension. The therapy effect is than compared to the recorded changes before the introduction of this therapy.

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis; Pulmonary Hypertension
• Intervention / Treatment: Drug: Bosentan

Detailed Description

Bosentan is an established therapy in pulmonary arterial hypertension, which may be diagnosed when the mean pulmonary arterial pressure is >25mmHg at rest or >30mmHg at exercise. Bosentan has shown efficacy, if mean pulmonary arterial pressure was elevated at rest. However, there are no data available of the effects of such a therapy, if the mean pulmonary arterial pressure is normal at rest but elevated during exercise. The purpose of this study is to provide additional data on this group of patients. Our hypothesis is that patients with exercise-induced pulmonary hypertension may show a gradual worsening of pulmonary hemodynamics and potentially a development of manifest pulmonary arterial hypertension (elevated resting pulmonary arterial pressure values) without treatment, while the introduction of Bosentan may improve hemodynamics and exercise capacity in this patient group.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Medical University of Graz, Pulmonology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• exercise-induced pulmonary hypertension
• systemic sclerosis

Exclusion Criteria:

• relevant pulmonary obstruction or restriction
• relevant left cardiac disease
• recent changes in medical therapy
• recent major operations
• recent major cardiovascular diseases
• inability to perform exercise

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Bosentan; In this study, all participants have normal pulmonary arterial pressure at rest and elevated pulmonary arterial pressure during exercise. First, they were followed up for a year and were controlled after 1 year without specific therapy for pulmonary hypertension. Then Bosentan was introduced. A second control showing the effects of the therapy was done after 6 months. The changes in the "therapy period" can be compared with the changes in the "follow up period".

Drug: Bosentan; 2x62.5mg for 4 weeks, then 2x125mg; Other Names: Tracleer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change of mean pulmonary arterial pressure at 50W under therapy with Bosentan compared to change of mean pulmonary arterial pressure at 50W before the introduction of therapy with Bosentan	12months before Bosentan therapy vs. at begin of bosentan therapy vs. 6months under bosentan therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
pulmonary vascular resistance, peak oxygen uptake	12months before Bosentan therapy vs. at begin of bosentan therapy vs. 6months under bosentan therapy

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Actelion

Publications and helpful links

General Publications

• Kovacs G, Maier R, Aberer E, Brodmann M, Graninger W, Kqiku X, Scheidl S, Troster N, Hesse C, Rubin L, Olschewski H. Pulmonary arterial hypertension therapy may be safe and effective in patients with systemic sclerosis and borderline pulmonary artery pressure. Arthritis Rheum. 2012 Apr;64(4):1257-62. doi: 10.1002/art.33460. Epub 2011 Nov 11.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 27, 2009
• First Submitted That Met QC Criteria: May 27, 2009
• First Posted (Estimate): May 28, 2009

Study Record Updates

• Last Update Posted (Estimate): September 23, 2011
• Last Update Submitted That Met QC Criteria: September 22, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Connective Tissue Diseases; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: 18-295 ex 06/07