Simvastatin as a Treatment for Pulmonary Hypertension

Study Overview
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Brief Summary
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The purpose of the study is to investigate the safety and efficacy of adding simvastatin to the current conventional treatment regimen for the management of pulmonary hypertension.

Detailed Description
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Pulmonary arterial hypertension (PAH) is a disease that is characterised by progressive narrowing of the blood vessels of the lungs. This results in a pressure load on the heart and heart failure. The narrowing is in part due to constriction but mostly due to structural changes in affected vessels. The structural changes affect all cell components of the vessel wall (the endothelial lining, the muscle layer and fibrous tissue) and can lead to local clot formation. In addition there is evidence of inflammation of the vessels and what is known as oxidative stress. The disease may occur with no obvious cause, when it is known as idiopathic, but it can also be associated with a variety of other diseases, including congenital heart disease, collagen vascular disease and HIV infection. Current approaches to the treatment of pulmonary hypertension are unsatisfactory as they do not prevent disease progression and do not directly or adequately address many of the processes detailed above. Alternative or additional treatments are therefore required and an attrative approach is to use a statin (a 3-hydroxy-3-methylglutaryl-coenzymeA, or HMG-CoA, reductase inhibitor). Statins are widely used for their ability to lower blood cholesterol but increasing evidence indicates that these drugs also have direct effects on cell components of the vessel wall - including inhibiting inflammation, clot formation and oxidative stress - that might be beneficial in pulmonary hypertension.

Official Title
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Simvastatin as a Treatment for Pulmonary Hypertension

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with idiopathic PAH or PAH related to collagen vascular disease Age 18 years or over Receiving conventional therapy with diuretics, digoxin, warfarin, sildenafil and bosentan. Stable for 1 month 6 minute walk distance between 150m and 450m Modified NYHA functional class II or III Exclusion Criteria: PAH from a cause other than permitted by entry criteria Change in PAH treatment in past 4 weeks Patients requiring prostanoid therapy Patients already taking a statin Clinically significant disturbance of liver function - AST or ALT >3xULM; bilirubin >1.5xULM Contraindication for a magnetic resonance scan

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1: Control<br>Placebo tablet once daily | Drug: Placebo<br>* Placebo tablet once daily.<br>|
| Experimental: Arm 2: Experimental<br>Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. | Drug: Simvastatin<br>* Simvastatin 40mg od for 1 month, then 80mg od for 11 months<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Right Ventricular Mass From Baseline | As measured by cardiac magnetic resonance (the study is powered to detect an 8.5g difference in RV mass between the two treatments, based on reproducibility measurements of RV mass in healthy volunteers and patients) | 6 months post study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-minute Walk Distance | Change in distance achieved in 6 minute walk test from baseline | 6 months | 
| Change in LV Mass | Change in LV mass from baseline based on cardiac MRI | 6 months | 
| Circulating Levels of BNP | Change in NT-proBNP levels compared to baseline | 6 months | 
| Change in Quality of Life Score | Change in quality of life score from baseline as measured by Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) scored from 1-25, with higher scores indicating worse quality of life, the investigator reported the score change. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary hypertension, Simvastatin, Statins