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ISRCTN
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ISRCTN03804536
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ClinicalTrials.gov identifier
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Public title
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The effect of reducing heart rate on central aortic blood pressure: a comparative study of ivabradine and atenolol on haemodynamic parameters at rest
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Scientific title
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Ethics approval was received from the local Cambridge medical ethics committee before trial recruitment began.
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Acronym
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N/A
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Serial number at source
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N0544183629
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Study hypothesis
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1. Hypothesis: heart rate reduction per se leads to an accentuation of central aortic pressure irrespective of the mechanism of heart rate reduction or changes in peripheral blood pressure.
2. Aims: we aim to test the above hypothesis by employing a pharmacological approach: comparing the haemodynamic effects of a beta-blocker (atenolol) and a heart rate limiting drug (ivabradine) in a placebo-controlled crossover trial (ie all participants will get placebo, atenolol and ivabradine at some stage). Heart rate, central and peripheral blood pressure, cardiac output and arterial stiffness (the 'haemodynamic parameters') will be assessed at baseline and up to 4 hours after each acute dosing.
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Ethics approval
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Not provided at time of registration
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Study design
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Placebo controlled crossover trial
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Cardiovascular: Haemodynamic parameters at rest
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Participants - inclusion criteria
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1. Volunteers aged 18-65
2. Subjects able to give informed consent
3. Normal blood pressure (< 140/90 mmHg but = 110/70 mmHg)
4. Resting heart rate = 50 beats per minute
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Participants - exclusion criteria
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1. Subjects with a history of hypertension or diabetes mellitus
2. Volunteers with a conduction defect on the ECG
3. Resting heart rate < 50 beats per minute and blood pressure < 110/70 mmHg
4. Pregnant women or those of childbearing age taking inadequate contraception
5. Volunteers with a history of asthma, cardiovascular disease or arrhythmias
6. Participants with a history of intolerance to beta-blockers or ivabradine
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Anticipated start date
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01/06/2006
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Anticipated end date
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01/07/2009
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Status of trial
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Completed |
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Patient information material
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Not available in web format, please use the contact details below to request a patient information sheet
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Target number of participants
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24 healthy volunteers
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Interventions
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STUDY DESCRIPTION
Up to 24 healthy people will be recruited in to the study via a poster asking for volunteers. The study will consist of 4 visits.
INCLUSION AND EXCLUSION CRITERIA
Visit 1 - Volunteers will be interviewed, examined and formal consent obtained. Height and weight will also be taken and a 12 lead electrocardiogram (ECG) performed. The GP will be informed with the subjects’ agreement.
Visit 2, 3 and 4 - Subjects will be asked to have a light breakfast (excluding tea, coffee, alcohol) and arrive by 8.30am. They will lie down and an intravenous cannula will be inserted into the forearm through which we will take blood. They will also be connected to a heart monitor. After an hour, baseline measurements will be taken. This involves applying a probe to the surface of the neck and the wrist. Via a computer and software programme, we can then assess central aortic pressure too. Haemodynamic parameters to be measured include: augmentation index, aortic and radial pulse wave velocity and analysis. These will be measured using the SphygmoCor system 2-Atcor Medical, Sydney, Australia. This will allow assessment of central aortic blood pressure using a validated transfer function. Electrodes placed on the chest will record heart rate. This will allow us to determine heart rate variability during specific times during the study with the SphymoCor HRV system. Similarly, cardiac output, stroke volume and cardiac index will be determined. Peripheral blood pressure will also be measured using a sphygmomanometer. Following this, we will take about 10-15ml of blood (approximately a tablespoonful) and send it for the measurement of sodium, potassium, calcium, creatinine, renin and aldosterone and catecholamines.
Then, subjects will be dosed with one of 3 pills orally: either atenolol 50mg, ivabradine 20mg or placebo (a dummy pill), but neither the volunteer nor the person doing the measurements will know which. Blood pressure readings will be repeated hourly and the blood tests at 4 hours. The final measurements will be made 4 hours post dosing, after which participants will be given food and drink and if the blood pressure and heart rate is acceptable, let home. Note that subjects are not permitted to eat or drink during the period of study. There will be a minimum 'washout' period of 3 days post which volunteers will attend for 2 more visits like the one described above but with different drugs (ie they will get all three types of pill during the course of the study).
ADVERSE EVENTS
Participants will be encouraged to report any adverse events and to contact members of the research team if they experience any problems. All serious adverse events will be reported to the Research and Development Department at Addenbrooke’s Hospital and other authorities as appropriate.
TERMINATION OF STUDY
The study will be ended when the last subject completes the study. Participants will be offered notification as to when any results might be published in the form of a scientific publication.
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Primary outcome measure(s)
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Assessing change in central blood pressure
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Secondary outcome measure(s)
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Assessing change in haemodynamic parameters
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Sources of funding
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Cambridge Consortium - Addenbrooke' s (UK), Departmental Funds, NHS R&D Support Funding
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Trial website
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Publications
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Contact name
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Dr
Ian
Wilkinson
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Address
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Lecturer and Honorary Consultant
Clinical Pharmacology Unit
Level 3, ACCI Building, Box 110
Addenbrooke's Hospital
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City/town
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Cambridge
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Zip/Postcode
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CB2 2QQ
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Country
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United Kingdom
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Tel
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+44 01223 336 806
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Fax
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+44 01223 216 893
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Email
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ibw20@cam.ac.uk
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Sponsor
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Record Provided by the NHSTCT Register - 2007 Update - Department of Health
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Address
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The Department of Health, Richmond House, 79 Whitehall
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City/town
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London
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Zip/Postcode
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SW1A 2NL
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Country
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United Kingdom
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Tel
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+44 (0)20 7307 2622
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Fax
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+44
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Email
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dhmail@doh.gsi.org.uk
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Sponsor website:
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http://www.dh.gov.uk/Home/fs/en
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Date applied
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28/09/2007
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Last edited
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10/09/2008
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Date ISRCTN assigned
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28/09/2007
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