Clinical trial NCT00180713: Simvastatin as a Treatment for Pulmonary Hypertension
Official title: Simvastatin as a Treatment for Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pulmonary Hypertension
Keywords: Pulmonary hypertension
Simvastatin
Statins
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: Medical Research Council
First posted: 2005-09-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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, 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

Primary outcomes:
measure: Change in Right Ventricular Mass From Baseline
timeFrame: 6 months post study treatment
Secondary outcomes:
measure: Change in 6-minute Walk Distance
timeFrame: 6 months
measure: Change in LV Mass
timeFrame: 6 months
measure: Circulating Levels of BNP
timeFrame: 6 months
measure: Change in Quality of Life Score
timeFrame: 6 months
Other outcomes:
Locations:
city: Gießen
country: Germany
facility: Department of Internal Medicine II, Klinikstrasse 36 D-35392
city: London
country: United Kingdom
facility: Royal Brompton Hospital, Sydney Street
city: London
country: United Kingdom
facility: Hammersmith Hospital, Du Cane Road
Study officials:
affiliation: Imperial College London
name: Martin Wilkins, MD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wilkins MR, Ali O, Bradlow W, Wharton J, Taegtmeyer A, Rhodes CJ, Ghofrani HA, Howard L, Nihoyannopoulos P, Mohiaddin RH, Gibbs JS; Simvastatin Pulmonary Hypertension Trial (SiPHT) Study Group. Simvastatin as a treatment for pulmonary hypertension trial. Am J Respir Crit Care Med. 2010 May 15;181(10):1106-13. doi: 10.1164/rccm.2009111-699oc.