Simvastatin as a Treatment for Pulmonary Hypertension
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Imperial College London
- Enrollment
- 42
- Locations
- 3
- Primary Endpoint
- Change in Right Ventricular Mass From Baseline
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Arm 1: Control
Placebo tablet once daily
Intervention: Placebo (Drug)
Arm 2: Experimental
Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months.
Intervention: Simvastatin (Drug)
Outcomes
Primary Outcomes
Change in Right Ventricular Mass From Baseline
Time Frame: 6 months post study treatment
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)
Secondary Outcomes
- Change in 6-minute Walk Distance(6 months)
- Change in LV Mass(6 months)
- Circulating Levels of BNP(6 months)
- Change in Quality of Life Score(6 months)