Pulmonary HypertensionPhase 1/2NCT00180713
Simvastatin as a Treatment for Pulmonary Hypertension
A Phase 1/2 study testing Simvastatin in people with Pulmonary Hypertension, run by Imperial College London at 3 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Hypertension
- What is being tested?
- Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Oct 2005to May 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United Kingdom2 sites
Royal Brompton Hospital, Sydney Street
London, SW3 6NP
Hammersmith Hospital, Du Cane Road
London, W12 0NN
Germany1 site
Department of Internal Medicine II, Klinikstrasse 36 D-35392
Giessen
About this study
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.
Read the 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.
- Conditions
- Pulmonary Hypertension
- Being tested
- Simvastatin, Placebo
- Keywords
- Pulmonary hypertension, Simvastatin, Statins
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Zocor
Simvastatin 40mg od for 1 month, then 80mg od for 11 months
PlaceboDrug
Placebo tablet once daily.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Control | Placebo comparator | Placebo tablet once daily Receives: Drug: Placebo |
| Arm 2: Experimental | Experimental | Simvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. Receives: Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 months post study treatment
Secondary outcomes (4)
Change in 6-minute Walk Distance
Change in distance achieved in 6 minute walk test from baseline
Measured: 6 months
Change in LV Mass
Change in LV mass from baseline based on cardiac MRI
Measured: 6 months
Circulating Levels of BNP
Change in NT-proBNP levels compared to baseline
Measured: 6 months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startOct 2005
- Primary completionOct 2008
- Study completionMay 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary HypertensionStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Medical Research Council
- Responsible party
- Sponsor
- Investigators
- Martin Wilkins, MD FRCP, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00180713
- Sponsor's protocol ID
- WILK10554
- Status last verified
- Aug 2019
- First submitted
- 12 Sep 2005
- Last updated
- 21 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 20460548
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Simvastatin as a Treatment for Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT00180713
- Acronym / sponsor ID
- WILK10554
- Conditions
- Pulmonary Hypertension
- Keywords
- Pulmonary hypertension, Simvastatin, Statins
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Medical Research Council
- Study start
- Oct 2005 (actual)
- Primary completion
- Oct 2008 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 21 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Control | Placebo comparator | Drug: PlaceboPlacebo tablet once daily |
| Arm 2: Experimental | Experimental | Drug: SimvastatinSimvastatin 40mg od for 1 month, then uptitrated to 80mg od for 11 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinAlso: ZocorSimvastatin 40mg od for 1 month, then 80mg od for 11 months | Drug | Arm 2: Experimental |
| PlaceboPlacebo tablet once daily. | Drug | Arm 1: Control |
Primary outcome
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)
4 secondary outcomes
Change in 6-minute Walk Distance
Time frame: 6 months
Change in LV Mass
Time frame: 6 months
Circulating Levels of BNP
Time frame: 6 months
Change in Quality of Life Score
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20460548Wilkins 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.
- Individual participant dataSharing planned: No
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A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Wilkins, MD FRCP principal investigator
Imperial College London
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Simvastatin in people with Pulmonary Hypertension, run by Imperial College London at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Right Ventricular Mass From Baseline (time frame: 6 months post study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00180713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2019.