Simvastatin as a Treatment for Pulmonary Hypertension

This study has been completed.
Sponsor:
Collaborator:
Medical Research Council
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00180713
First received: September 12, 2005
Last updated: July 6, 2009
Last verified: July 2009
  Purpose

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
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Simvastatin as a Treatment for Pulmonary Hypertension

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Right ventricular mass 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) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 6-minute walk distance [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • LV systolic eccentricity index, tie index and right atrial area as measured by echocardiography [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Circulating levels of BNP and inflammatory markers (e.g. MCP-1) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Urinary iPF 2 alpha III levels [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Occurrence of adverse effects (total and severe, symptomatic and biochemical) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Quality of life (as measured by CAMPHOR) [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]
  • Cardiac output and measures of RV function as measured by cardiac magnetic resonance [ Time Frame: 6 months, 12 months ] [ Designated as safety issue: No ]

Enrollment: 42
Study Start Date: October 2005
Study Completion Date: May 2009
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
Placebo tablet once daily
Drug: Placebo
Placebo tablet once daily.
Other Name: Placebo
Experimental: 2
Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months.
Drug: Simvastatin
Simvastatin 40mg od for 1 month, then 80mg od for 11 months
Other Name: Zocor

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00180713

Locations
Germany
Department of Internal Medicine II
Klinikstrasse 36 D-35392 Giessen, Germany
United Kingdom
Hammersmith Hospital, Du Cane Road
London, United Kingdom, W12 0NN
Royal Brompton Hospital, Sydney Street
London, United Kingdom, SW3 6NP
Sponsors and Collaborators
Imperial College London
Medical Research Council
Investigators
Principal Investigator: Martin Wilkins, MD FRCP Imperial College London
  More Information

No publications provided by Imperial College London

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mr Gary Roper, Research Governance Manager, Imperial College London
ClinicalTrials.gov Identifier: NCT00180713     History of Changes
Other Study ID Numbers: WILK10554
Study First Received: September 12, 2005
Last Updated: July 6, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
Pulmonary hypertension
Simvastatin
Statins

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Simvastatin
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014