Condition category
Circulatory System
Date applied
19/09/2008
Date assigned
27/10/2008
Last edited
09/06/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Mark Harbinson

ORCID ID

Contact details

Department of Therapeutics and Pharmacology
Whitla Medical Building
Lisburn Road
Belfast
BT9 7BL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Sponsors ref: 07009GM-A

Study information

Scientific title

Effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibition on endothelial dysfunction, bioavailability of tetrahydrobiopterin (BH4) and functional regulation of endothelial nitric oxide synthase (eNOS) in human heart failure

Acronym

Study hypothesis

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A) reductase inhibitors in patients with heart failure will result in reduced uncoupling of endothelial nitric oxide synthase (eNOS), detected biochemically by increased production of nitric oxide and reduced production of free radicals and functionally by improved flow mediated dilatation of the brachial artery and changes in velocity time waveforms; and that these changes can be explained in part by detection of increased levels of tetrahydrobiopterin (BH4).

Ethics approval

Health and Social Care Research Ethics Committee 1, 28/10/2008, ref: 08/NIR01/74

Study design

Parallel group double-blind randomised placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Heart failure with systolic dysfunction

Intervention

Simvastatin 40 mg orally (or placebo) once a day (in the evening) will be administered for 6 weeks to each study participant.

Intervention type

Drug

Phase

Not Applicable

Drug names

Simvastatin

Primary outcome measures

Changes in levels of superoxide, peroxynitrite, nitric oxide, tetrahydrobiopterin and brachial artery flow mediated dilatation and pulse contour analysis. Each outcome measure will be assessed at an initial visit, and then following randomisation and 6 weeks of treatment.

Secondary outcome measures

Changes in levels of markers of left ventricular (LV) dysfunction, adrenomedullin, N-terminal prohormone brain natriuretic peptide (NT proBNP) and intermedin. Each outcome measure will be assessed at an initial visit, and then following randomisation and 6 weeks of treatment.

Overall trial start date

01/11/2008

Overall trial end date

30/11/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Both males and females, over 18 years of age
2. Diagnosis of heart failure with an ejection fraction less than 35% determined by 2D echocardiography. Patients will be typically receiving maximal therapy for treatment of heart failure, including loop diuretics, angiotensin converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers and spironolactone.
3. Patients must also be able to give informed consent, and to attend for follow up appointments

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

60

Participant exclusion criteria

1. History of diabetes mellitus (fasting glucose greater than 7 mmol/L) or uncontrolled hypertension (blood pressure [BP] greater than 140/90 mmHg) or are receiving the thienopyridine derivative clopidogrel
2. Abnormal liver function (defined as aspartate aminotransferase [AST] or alanine aminotransferase [ALT] greater than three times upper limit of normal) or have had a previous documented adverse reaction to statin therapy or hypersensitivity to simvastatin or any of the excipients
3. Pregnant or lactating
4. Any patient who has an adverse reaction to statin therapy following initiation of treatment
5. Patients taking potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, human immunodeficiency virus [HIV] protease inhibitors, erythromycin, clarithromycin)
6. Patients taking cyclosporin, gemfibrozil or greater than 1 g/day niacin

Recruitment start date

01/11/2008

Recruitment end date

30/11/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Therapeutics and Pharmacology
Belfast
BT9 7BL
United Kingdom

Sponsor information

Organisation

Belfast Health and Social Care Trust (UK)

Sponsor details

Postgraduate Office
Belfast City Hosptial
Lisburn Road
Belfast
BT7 9AB
United Kingdom

Sponsor type

Government

Website

http://www.belfasttrust.hscni.net

Funders

Funder type

Government

Funder name

Research and Development Office of the Central Services Agency, Northern Ireland (UK) (ref: EAT/3719/07)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

09/06/2016: No publications found, verifying study status with principal investigator. 08/05/2013: The anticipated end date for this trial was updated from 03/08/2010 to 30/11/2011 09/02/2009: This record was updated to include an amended anticipated start date. The initial anticipated start date was 06/08/2008.