Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to determine whether carvedilol treatment of patients with pulmonary arterial hypertension and associated right heart failure is safe and results in an improved function of the right heart.

Detailed Description
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Patients with pulmonary arterial hypertension (PAH) will be treated with carvedilol for 24 weeks. During this time, carvedilol will be titrated from an initial dose of 3.125mg BID to a maximal dose of 25mg BID. At the start and end of the study, we will obtain cardiac MRI, 6 minute walk distance, brain natriuretic peptide (serum), echocardiogram, and functional class assessment. Our primary outcome is a change in right ventricular ejection fraction with cardiac MRI.

Official Title
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Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Carvedilol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: idiopathic, familial or associated PAH, WHO group 1 NYHA class II or III clinically stable with optimized PAH treatment for at least 3 months no or minimal evidence of fluid overload or volume depletion, with or without diuretic treatment age > 18 years mean pulmonary artery pressure (mPAP) > 25 mmHg 6 minute walk distance (6MWD) over 100m Exclusion Criteria: Structural heart disease unrelated to PAH Recent (<3 months) treatment with an intravenous positive inotropic agent current use of β-blockers history of reactive airways disease history of adverse reaction to β-blockers heart block on ECG or resting heart rate < 60 bpm cardiac index < 1.8 l/min/m2 systemic hypotension (systolic pressure < 90 mmHg) pulmonary capillary wedge pressure > 15 mmHg inability to give informed consent contraindications to CT and/or PET scanning coagulopathy (INR>1.5 or platelet count<50000/mm3) severe renal insufficiency (creatinine clearance <30 ml/min/m2) malignancy or any co-morbidity limiting survival or conditions predicting inability to complete the study.

Ages Eligible for Study
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Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carvedilol<br>Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI | Drug: Carvedilol<br>* twice daily oral treatment in escalating dose<br>* Other names: Coreg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Right Ventricular Ejection Fraction | Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only | baseline, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Right Ventricular End Systolic Volume | right ventricular end systolic volume determined by MRI | baseline and 6 months | 
| Change in 6 Minute Walk Distance |  | baseline and 6 months | 
| Change in Tricuspid Annular Plane Systolic Excursion | Higher values indicate a better outcome. | baseline and 6 months |