A randomised controlled trial of the angiotensin converting enzyme (ACE) inhibitor ramipril in asymptomatic aortic stenosis

ISRCTN	ISRCTN24616095
DOI	https://doi.org/10.1186/ISRCTN24616095
EudraCT/CTIS number	2007-005224-32
Secondary identifying numbers	N0176135469 / OCMR 06.01

Submission date: 30/09/2004
Registration date: 30/09/2004
Last edited: 24/03/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Background and study aims
For patients with aortic stenosis (a narrowing of the main valve out of the heart), the only effective treatment currently is valve replacement surgery. A group of drugs called ACE inhibitors are of proven benefit in treating heart failure from other causes and reducing increased heart muscle thickness, both of which occur in aortic stenosis. They are however considered to be contraindicated in aortic stenosis, despite a lack of evidence for harm. The aim of our study is to determine whether an ACE inhibitor has any beneficial effects in patients with aortic stenosis.

Who can participate?
Men and women aged over 18 years with aortic stenosis.

What does the study involve?
Participants will be randomly allocated to receive either the ACE inhibitor ramipril or a placebo (dummy) drug.

What are the possible benefits and risks of participating?
Not provided at time of registration.

Where is the study run from?
John Radcliffe Hospital (UK).

When is the study starting and how long is it expected to run for?
The study ran from October 2008 to December 2011.

Who is funding the study?
1. Heart Research UK (UK)
2. Oxford Comprehensive NIHR Biomedical Research Centre (UK)
3. Department of Health Technology Platform Grant for Advanced Imaging (UK)

Who is the main contact?
Dr Saul Myerson
saul.myerson@cardiov.ox.ac.uk

Contact information

Dr Saul Myerson
Scientific

Department of Cardiovascular Medicine
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Phone	+44 (0)1865 220245
Email	saul.myerson@cardiov.ox.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A randomised controlled trial of the angiotensin converting enzyme (ACE) inhibitor ramipril in asymptomatic aortic stenosis
Study acronym	RIAS
Study hypothesis	Patients with narrowed aortic valves (the main valve affecting blood flow out of the heart) sometimes develop symptoms of breathlessness or reduced heart function, and this is often accompanied by a thickened heart muscle. This muscle thickening may actually be detrimental to cardiac function, through increased stiffness, and a reduction of this may be beneficial to the patients. A group of drugs called ACE inhibitors are of proven benefit in reducing heart muscle thickness from other causes, and also improve cardiac function and prolong life in patients with heart failure. We propose a randomised placebo-controlled trial of one ACE inhibitor, ramipril, in patients with narrowed aortic valves to determine if this can reduce muscle thickness, delay the onset symptoms and the need for valve replacement surgery. On 21/05/2010 the trial record was updated to add the sources of funding.
Ethics approval(s)	Oxfordshire REC C, 06/11/2007, ref: 07/H0606/139
Condition	Cardiovascular: asymptomatic aortic stenosis
Intervention	Factory-prepared randomised packs of identical placebo/ramipril tablets. Initial supply for 2 weeks, then further supply at the second clinic visit, to allow for up-titration of ramipril dose. Randomisation data sealed and unopened until after data analysis at end. Added 19/05/2010: trial started in 2008 instead of 2002.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ramipril
Primary outcome measure	1. Safety of administration in this group of patients 2. Changes in left ventricular mass and function
Secondary outcome measures	Added 21/05/2010: 1. Change in left ventricular ejection fraction 2. Change in other LV functional parameters assessed by MRI 3. Change in biochemical markers of LV function (BNP) 4. Change in myocardial energetics measured with magnetic resonance spectroscopy 5. Time to symptoms of aortic stenosis or aortic valve replacement 6. Change in distance walked and maximal effort tolerance on exercise treadmill testing
Overall study start date	01/10/2008
Overall study end date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	100 patients
Participant inclusion criteria	Added 21/05/2010: 1. Male or female, aged 18 years or above 2. Diagnosed with asymptomatic aortic stenosis of at least moderate degree (peak velocity ≥3.0 m/sec; gradient ≥36 mmHg or valve area <1.5 cm2 by echocardiography) for whom aortic valve replacement surgery is currently not contemplated 3. Left ventricular ejection fraction on echocardiography ≥40% without regional wall motion abnormality suggestive of significant previous myocardial infarction 4. Patient is willing and able to give informed consent for participation in the study 5. Able (in the investigators' opinion) and willing to comply with all study requirements
Participant exclusion criteria	Added 21/05/2010: 1. Other significant valve disease 2. Female who is pregnant, lactating or planning pregnancy during the course of the study 3. Significant renal impairment (estimated GFR < 30 ml/min). If moderate renal impairment (GFR 30-59 ml/min) is present, patients may be included in the study, but will not receive gadolinium contrast during the CMR scan 4. Known hepatic impairment (AST/ALT > 2 times the upper limit of normal) 5. Prescription of ACE inhibitors or angiotensin II receptor blockers (ARBs) within the 3 months prior to the start of the study 6. Past history of an allergic reaction or intolerance to ACE inhibitors 7. Sustained systolic blood pressure <100 mmHg or >200 mmHg or diastolic blood pressure <40 mmHg or >110 mmHg at baseline measurement 8. Contraindication to magnetic resonance scanning (pacemaker, cranial aneurysm clips, metallic ocular foreign bodies, severe claustrophobia) 9. Patient is terminally ill 10. Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient ability to participate in the study 11. Patients who have participated in another research study involving an investigational product in the past 3 months
Recruitment start date	01/10/2008
Recruitment end date	31/12/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Department of Cardiovascular Medicine

Oxford
OX3 9DU
United Kingdom

Sponsor information

University of Oxford (UK)
Government

University Offices
Wellington Square
Oxford
OX1 2JD
United Kingdom

Email	abc@email.com
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Research organisation

Heart Research UK (UK)
Private sector organisation / Other non-profit organizations

Location: United Kingdom

Oxford Comprehensive NIHR Biomedical Research Centre (UK)

No information available

Department of Health Technology Platform Grant for Advanced Imaging (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/08/2015		Yes	No