Condition category
Circulatory System
Date applied
22/12/2017
Date assigned
24/01/2018
Last edited
08/03/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Contact information

Type

Scientific

Primary contact

Prof Glezer Maria

ORCID ID

Contact details

Department of Preventive and Emergency Cardiology
Sechenov First Moscow State Medical University
2-4 Bolshaya Pirogovskaya st.
Moscow
119991
Russian Federation

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

Sponsor information

Organisation

Servier Affaires Medicales

Sponsor details

35 rue de Verdun
Suresnes
92284
France

Sponsor type

Industry

Website

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

Publication citations

Additional files

Editorial Notes

08/03/2018: Publication reference added.