Simvastatin as a Treatment for Pulmonary Hypertension

Pulmonary Hypertension Clinical Trial

Official title:

Simvastatin as a Treatment for Pulmonary Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00180713
• Other study ID #: WILK10554
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2005
• Est. completion date: May 2009

Study information

• Verified date: August 2019
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 2009
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• Simvastatin
Simvastatin 40mg od for 1 month, then 80mg od for 11 months
• Placebo
Placebo tablet once daily.

Locations

Country	Name	City	State
Germany	Department of Internal Medicine II, Klinikstrasse 36 D-35392	Gießen
United Kingdom	Hammersmith Hospital, Du Cane Road	London
United Kingdom	Royal Brompton Hospital, Sydney Street	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Medical Research Council

Countries where clinical trial is conducted

Germany,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in 6-minute Walk Distance	Change in distance achieved in 6 minute walk test from baseline	6 months
Secondary	Change in LV Mass	Change in LV mass from baseline based on cardiac MRI	6 months
Secondary	Circulating Levels of BNP	Change in NT-proBNP levels compared to baseline	6 months
Secondary	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