Condition category
Circulatory System
Date applied
28/09/2007
Date assigned
28/09/2007
Last edited
14/09/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Ian Wilkinson

ORCID ID

Contact details

Lecturer and Honorary Consultant
Clinical Pharmacology Unit
Level 3
ACCI Building
Box 110
Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom
+44 01223 336 806
ibw20@cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0544183629

Study information

Scientific title

Ethics approval was received from the local Cambridge medical ethics committee before trial recruitment began.

Acronym

Study hypothesis

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.

Ethics approval

Not provided at time of registration

Study design

Placebo controlled crossover trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Condition

Cardiovascular: Haemodynamic parameters at rest

Intervention

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.

14/09/2012: Please note that this trial was stopped due to poor recruitment

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.

Intervention type

Drug

Phase

Not Specified

Drug names

ivabradine and atenolol

Primary outcome measures

Assessing change in central blood pressure

Secondary outcome measures

Assessing change in haemodynamic parameters

Overall trial start date

01/06/2006

Overall trial end date

01/07/2009

Reason abandoned

Participant recruitment issue

Eligibility

Participant inclusion criteria

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

Participant type

Patient

Age group

Adult

Gender

Not Specified

Target number of participants

24 healthy volunteers

Participant exclusion criteria

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

Recruitment start date

01/06/2006

Recruitment end date

01/07/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Lecturer and Honorary Consultant
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

Record Provided by the NHSTCT Register - 2007 Update - Department of Health

Sponsor details

The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk

Sponsor type

Government

Website

http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Funder name

Cambridge Consortium - Addenbrooke' s (UK), Departmental Funds, NHS R&D Support Funding

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