Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Simvastatin as a Treatment for Pulmonary Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00180713
Recruitment Status : Completed
First Posted : September 16, 2005
Results First Posted : August 21, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
Medical Research Council
Information provided by (Responsible Party):
Imperial College London

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Pulmonary Hypertension Drug: Simvastatin Drug: Placebo Phase 1 Phase 2

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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Simvastatin as a Treatment for Pulmonary Hypertension
Actual Study Start Date : October 2005
Actual Primary Completion Date : October 2008
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Placebo Comparator: Arm 1: Control
Placebo tablet once daily
 Drug: Placebo
Placebo tablet once daily.
Experimental: Arm 2: Experimental
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


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Change in 6-minute Walk Distance [ Time Frame: 6 months ]
    Change in distance achieved in 6 minute walk test from baseline

  2. Change in LV Mass [ Time Frame: 6 months ]
    Change in LV mass from baseline based on cardiac MRI

  3. Circulating Levels of BNP [ Time Frame: 6 months ]
    Change in NT-proBNP levels compared to baseline

  4. Change in Quality of Life Score [ Time Frame: 6 months ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00180713


Locations
Layout table for location information
Germany
Department of Internal Medicine II, Klinikstrasse 36 D-35392
Gießen, Germany
United Kingdom
Royal Brompton Hospital, Sydney Street
London, United Kingdom, SW3 6NP
Hammersmith Hospital, Du Cane Road
London, United Kingdom, W12 0NN
Sponsors and Collaborators
Imperial College London
Medical Research Council
Investigators
Layout table for investigator information
Principal Investigator: Martin Wilkins, MD FRCP Imperial College London
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Layout table for additonal information
Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT00180713    
Other Study ID Numbers: WILK10554
First Posted: September 16, 2005    Key Record Dates
Results First Posted: August 21, 2019
Last Update Posted: August 21, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Imperial College London:
Pulmonary hypertension
Simvastatin
Statins
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension, Pulmonary
Hypertension
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Simvastatin
 Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors