Bosentan for Severe Mitral Valve Dysfunction

Study Overview
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Brief Summary
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Vasoconstrictive signaling via endothelin receptors is not limited to primary pulmonary arterial hypertension, but has also been documented in secondary pulmonary hypertension due to congestive heart failure, including cardiac valve disease. The investigators aim to examine the clinical and physiologic effects of bosentan therapy in patients with secondary pulmonary hypertension due to severe, inoperable cardiac valve disease, using a single-center, prospective, open-label, non-randomized study of oral bosentan in outpatients with severe mitral stenosis due to childhood rheumatoid fever. Primary end-point will be exercise capacity at six months determined by six-minute walking distance and cardiopulmonary exercise testing. Secondary end-points will be symptomatic relief, echocardiographic left ventricular function and pulmonary pressure, serum pro-brain natriuretic peptide, and adverse events at six months.

Official Title
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Pilot Trial of Bosentan for Secondary Pulmonary Hypertension Due to Severe Mitral Valve Dysfunction

Conditions
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MITRAL STENOSIS, SECONDARY PULMONARY HYPERTENSION, CHILDHOOD RHEUMATOID FEVER, CONGESTIVE HEART FAILURE

Intervention / Treatment
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* Drug: BOSENTAN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient > 60 Yrs Old < 85 Yrs Old Stable disease Congestive heart failure NYHA IIIB/V Inoperable mitral stenosis due to childhood rheumatoid fever Mean pulmonary artery pressure > 40 cm H2O Exclusion Criteria: Prior treatment with endothelin receptor antagonist(s) Hospitalization (exacerbation) Cardiac valve surgery

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: BOSENTAN|TWICE DAILY PERORAL BOSENTAN, 125 MG DAILY DIVIDED IN TWO DOSES DURING THE FIRST MONTH AND 250 MG DAILY DIVIDED IN TWO DOSES SUBSEQUENTLY.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SIX MINUTE WALKING DISTANCE | CHANGE IN SIX MINUTE WALKING DISTANCE AFTER 6 MONTHS OF THERAPY COMPARED TO PRE-TREATMENT VALUE. | SIX MONTHS | 
| MAXIMAL OXYGEN UPTAKE | CHANGE IN MAXIMAL OXYGEN UPTAKE AFTER 6 MONTHS OF THERAPY COMPARED TO PRE-TREATMENT VALUE. | 6 MONTHS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ECHOCARDIOGRAPHIC PULMONARY PRESSURE | ECHOCARDIOGRAPHIC ASSESSMENT OF PEAK AND MEAN PULMONARY PRESSURE AT 6 MONTHS AFTER TREATMENT COMPARED WITH PRE-TREATMENT VALUES. | 6 MONTHS | 
| ECHOCARDIOGRAPHIC LEFT VENTRICULAR FUNCTION | ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT VENTRICULAR FUNCTION AT 6 MONTHS AFTER TREATMENT COMPARED WITH PRE-TREATMENT VALUES. | 6 MONTHS | 
| SERUM PRO-BNP | ASSESSMENT OF SERUM PRO-BRAIN NATRIURETIC PEPTIDE LEVELS AT 6 MONTHS AFTER TREATMENT COMPARED WITH PRE-TREATMENT VALUES. | 6 MONTHS | 
| DYSPNEA | CHANGE IN BORG DYSPNEA INDEX COMPARED WITH PRE-TREATMENT VALUES. | 6 MONTHS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ENDOTHELIN RECEPTOR ANTAGONIST, BOSENTAN, SECONDARY PULMONARY HYPERTENSION, RHEUMATOID FEVER, CONGESTIVE HEART FAILURE, SECONDARY PULMONARY HYPERTENSION DUE TO MITRAL STENOSIS