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.

Condition	Intervention	Phase
Pulmonary Hypertension	Drug: Simvastatin	Phase I Phase II

Further Study Details: 

Primary Outcomes: Pulmonary artery pressure; Pulmonary vascular pressure; Pulmonary vascular resistance; Cardiac output; Right ventricle mass (measures by caridac magnetic resonance)
Secondary Outcomes: 6-minute walk distance; LY systolic eccentricity index, tie index and right atrial area as measured by echocardiography; Circulating levels of BNP and inflammatory markers (e.g. MCP-1); Urinary iPF 2 alpha III levels; Occurrence of adverse effects (total and severe, symptomatic and biochemical)
Expected Total Enrollment:  60

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 stresss. 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 vascualr 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-methlglutaryl-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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00180713

Martin Wilkins, MD FRCP      +44 (0)20 8383 2049    m.wilkins@imperial.ac.uk

United Kingdom
      Hammersmith Hospital, Du Cane Road, London,  W12 0NN,  United Kingdom
      Royal Brompton Hospital, Sydney Street, London,  SW3 6NP,  United Kingdom

Study chairs or principal investigators

Martin Wilkins, MD FRCP,  Principal Investigator,  Imperial College London   

Study ID Numbers:  WILK10554
Last Updated:  September 15, 2005
Record first received:  September 12, 2005
ClinicalTrials.gov Identifier:  NCT00180713
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
ClinicalTrials.gov processed this record on 2005-09-20