Efficacy of ivabradine in combination with beta-blockers vs up-titration of beta-blockers in daily practice
| ISRCTN | ISRCTN30654443 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN30654443 |
| Secondary identifying numbers | N/A |
- Submission date
- 22/12/2017
- Registration date
- 24/01/2018
- Last edited
- 08/03/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Plain English summary of protocol
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
Contact information
Scientific
Department of Preventive and Emergency Cardiology
Sechenov First Moscow State Medical University
2-4 Bolshaya Pirogovskaya st.
Moscow
119991
Russian Federation
Study information
| Study design | Multicentre open randomised prospective study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Efficacy of ivabradine in combination with beta-blockers vs up-titration of beta-blockers in daily practice |
| Study acronym | Control-2 |
| Study objectives | 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(s) | Ethic approval was obtained before recruitment of the first participants |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Ivabradine |
| Primary outcome measure | 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 study start date | 01/08/2008 |
| Completion date | 30/01/2011 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 1104 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 02/11/2009 |
| Date of final enrolment | 30/12/2009 |
Locations
Countries of recruitment
- Russian Federation
Study participating centre
2-4 Bolshaya Pirogovskaya st
Moscow
119991
Russian Federation
Sponsor information
Industry
35 rue de Verdun
Suresnes
92284
France
"ROR" |
https://ror.org/034e7c066 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 22/11/2011 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | |
| IPD sharing plan | The datasets generated during the current study are not publicly available but are available from the corresponding author on reasonable request. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | Yes | No | ||
| Results article | results | 01/03/2018 | Yes | No |
Editorial Notes
08/03/2018: Publication reference added.
