Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.

Study Overview
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Brief Summary
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Pulmonary arterial hypertension is a chronic disease of the lung blood vessels resulting in constriction and high pressures. Treatment is given with a variety of drugs including the prostanoid class (e.g. epoprostenol, iloprost and the phosphodiesterase 5 (PDE-5) inhibitors (e.g. sildenafil). Although these drugs are known to be effective alone, little is known about combining them together in various combinations. In this trial we will add a long-acting PDE-5 inhibitor to the treatment of patients with pulmonary arterial hypertension who currently are receiving only a prostanoid drug.

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Tadalafil
* Drug: Vardenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must satisfy current diagnostic criteria for pulmonary artery hypertension based on their historical right heart catheter data (within 3 years of study enrollment): Mean PAP >25mmHg at rest or >30mmHg with exercise, by a PCWP< 15mmHg and by PVR >3 Wood Units. Currently stable for at least 3 months on prostanoid monotherapy (epoprostenol iv or iloprost inhaled). Willing and able to participate in all study follow-up procedures. New York Heart Association (NYHA) Class II-IV. Six minute walking distance between 100-450 meters at the baseline assessment. Women of child-bearing age must demonstrate adequate contraception or undergo a pregnancy test. Patients with congenital heart disease are eligible for inclusion. Exclusion Criteria: Functional Class NYHA Class I. PAH due to chronic pulmonary thromboembolic disease, left heart disease, chronic lung diseases (VC or FEV1 < 60% of predicted) or chronic hypoxia. Acute intercurrent illness requiring hospital admission in the month proceeding screening. Any non-PAH medical condition likely to interfere with participation in evaluation of study endpoints, e.g. musculoskeletal disorders. Any uncontrolled or terminal non-PAH medical condition likely to interfere with completion of the study, according to the judgment of the study physician. Concomitant therapy with drugs known to interact adversely with the study drug. Chronic renal failure - creatinine clearance <50ml/min as calculated with the Cockcroft equation. Current participation in another clinical trial. Pregnancy or planned pregnancy during the study period.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Patients treated with epoprostenol (Flolan) will be given tadalafil (Cialis). | Drug: Tadalafil<br>* Orally, titrated to maximum 20mg od<br>* Other names: Cialis;|
| Experimental: 2<br>Patients receiving iloprost (Ventavis) will receive vardenafil (Levitra) | Drug: Vardenafil<br>* Orally, titrated to 10 mg bid<br>* Other names: Levitra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six minute walking distance |  | 12 weeks | 
| Level of pro-NT BNP |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echo-derived parameters |  | 12 weeks | 
| Cardiopulmonary exercise test |  | 12 weeks |