Plain English Summary
Background and study aims
Angina is chest pain that occurs when the blood supply to the muscles of the heart is restricted. It affects more than a hundred million patients in the world, and although treatments exist the disease is not always optimally controlled. Heart rate reduction is important part of treatment. This study compares the effectiveness and tolerability of the combination of beta-blockers with ivabradine versus increased dose of beta-blockers up to the maximum tolerated dose.
Who can participate?
Patients aged 18 and over with stable angina undergoing regular treatment with beta-blockers
What does the study involve?
Patients are randomly allocated to either standard therapy with increased dose of beta-blockers up to the maximum tolerated dose, or ivabradine is added to their current beta-blockers dose. There are five clinic visits: at the start of the study (Visit 0), 2 weeks (Visit 1), 4 weeks (Visit 2), 8 weeks (Visit 3) and 16 weeks (Visit 4).
What are the possible benefits and risks of participating?
The results of a previous study demonstrated the effectiveness and good tolerability of this combination. At the same time tolerability problems which could limit increasing the dose of beta-blockers are well known in clinical practice.
Where is the study run from?
Sechenov First Moscow State Medical University (Russia)
When is the study starting and how long is it expected to run for?
August 2008 to January 2011
Who is funding the study?
Servier Affaires Medicales (France)
Who is the main contact?
Prof. Glezer Maria
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Efficacy of ivabradine in combination with beta-blockers vs up-titration of beta-blockers in daily practice
Acronym
Control-2
Study hypothesis
Heart rate (HR) reduction is an integral part of anti-anginal therapy, but many patients do not reach the guidelines-recommended target of <60 bpm despite high use of beta-blockers (BB). Failure to up-titrate BB doses may be partly to blame. Randomised controlled studies showed that addition of ivabradine to a beta-blocker in patients with stable angina reduced angina symptoms and improved exercise capacity compared with beat-blocker alone. The larger experience in patients from daily practice will help to understanding about the broader potential for combination treatment with ivabradine and BBs.
Ethics approval
Ethic approval was obtained before recruitment of the first participants
Study design
Multicentre open randomised prospective study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Stable angina
Intervention
For this trial, there wasn’t a central randomization procedure. Each investigator was provided with a table of randomization. Consecutive patients were allocated to standard therapy with BB up-titration to the maximal tolerated dose or ivabradine was added to their current BB dose, in a 1:4 ratio of patients. Up-titration of BB was carried out according to achieved resting HR and tolerability as, in contrast to heart failure, there is no recommended target dose or recommended BB molecule in treating stable angina, and thus a wide variety of agents and doses are commonly used. Five clinic visits were performed: baseline (Visit 0), 2 weeks (Visit 1), 4 weeks (Visit 2), 8 weeks (Visit 3) and 16 weeks (Visit 4).
Intervention type
Drug
Phase
Not Applicable
Drug names
Ivabradine
Primary outcome measures
Measured at baseline (Visit 0), 2 weeks (Visit 1), 4 weeks (Visit 2), 8 weeks (Visit 3) and 16 weeks (Visit 4):
1. Change in heart rate during the 16-week treatment period
2. Change in CCS class of angina
3. Number of angina attacks with standard therapy vs ivabradine
4. Proportion of patients who were angina-free between study visits
5. Patient self-reported health status, measured using the visual analogue scale (VAS)
Secondary outcome measures
There are no secondary outcome measures
Overall trial start date
01/08/2008
Overall trial end date
30/01/2011
Reason abandoned
Eligibility
Participant inclusion criteria
1. Adult patients (≥18 years)
2. Documented angina of effort, Canadian Cardiovascular Society (CCS) class II-III, which has been stable for at least three months, with ≥3 attacks per week
3. In sinus rhythm with HR ≥60 bpm
4. Undergoing regular treatment of stable angina with a BB in a dose which was below the maximum for angina treatment
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
1104
Participant exclusion criteria
1. Chronic heart failure of NYHA class III-IV
2. Non-sinus rhythm
3. Blood pressure >180/100 mm Hg at rest
4. Treatment with verapamil or diltiazem
Recruitment start date
02/11/2009
Recruitment end date
30/12/2009
Locations
Countries of recruitment
Russian Federation
Trial participating centre
Sechenov First Moscow State Medical University
Department of Preventive and Emergency Cardiology
2-4 Bolshaya Pirogovskaya st
Moscow
119991
Russian Federation
Funders
Funder type
Industry
Funder name
Servier Affaires Medicales
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
IPD sharing statement
The datasets generated during the current study are not publicly available but are available from the corresponding author on reasonable request.
Intention to publish date
22/11/2011
Participant level data
Available on request
Results - basic reporting
Publication summary
2011 results in: http://www.scardio.ru/izdaniya/zhurnal_kardiovaskulyarnaya_terapiya_i_profilaktika/arhiv_zhurnala_kardiovaskulyarnaya_terapiya_i_profilaktika/2011/soderzhanie_vypuska__8_2011/ (in Russian)
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29508153