Evaluation of the anti-anginal efficacy and safety of oral administration of ivabradine compared to placebo on top of a background therapy with a calcium antagonist (amlodipine or nifedipine) in patients with stable angina pectoris: A 6-week, randomised, double-blind, parallel-group, international, multicentre study
| ISRCTN | ISRCTN18979472 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18979472 |
| EudraCT/CTIS number | 2006-006246-34 |
| Secondary identifying numbers | CL3-16257-068 |
- Submission date
- 26/12/2007
- Registration date
- 18/07/2008
- Last edited
- 21/04/2020
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration and not expected to be available in the future
Contact information
Prof Gabriel Kamensky
Scientific
Scientific
Faculty Hospital Ruzinov
Department of Non-Invasive Cardiology
Ruzinovska 6
Bratislava
SR-82606
Slovakia
Study information
| Study design | Randomised, double-blind, parallel-group ,international, multi-centre study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | Evaluation of the anti-anginal efficacy and safety of oral administration of ivabradine compared to placebo on top of a background therapy with a calcium antagonist (amlodipine or nifedipine) in patients with stable angina pectoris. A 6-week randomised double-blind parallel-group international multicentre study. |
| Study hypothesis | To demonstrate that over a 6-week treatment period ivabradine is more efficacious than placebo when given in combination with calcium antagonists (amlodipine or nifedipine) in patients with stable chronic effort angina pectoris. As of 23/07/2012 the anticipated end date for this trial has been updated from 30/01/2012 to 31/01/2013 As of 03/03/2011 the anticipated end date for this trial has been updated from 15/11/2009 to 30/01/2012. |
| Ethics approval(s) | First Latvian Ethics Committee, 14/09/2007 |
| Condition | Angina pectoris |
| Intervention | All participants will be given either: a. 5 mg/day amlodipine (oral) for 6 weeks or b. 30 mg/day nifedipine GastroIntestinal Therapeutic System (GITS) (oral) for 6 weeks In addition, they will be given either ivabradine or placebo according to random allocation: Group 1: 5 mg twice a day (bid) ivabradine for 2 weeks then uptitration to 7.5 mg bid (except if HR< 60 bpm and/or symptomatic bradycardia) for 4 weeks Group 2: Placebo daily for 6 weeks |
| Intervention type | Other |
| Primary outcome measure | Response to treatment, evaluated over a 6-week treatment period, will be defined as a decrease of at least 3 angina attacks per week and/or an increase in the time to 1 mm ST segment depression of at least 60 s during a treadmill Exercise Tolerance Test (ETT), performed according to a modified Bruce protocol at the trough of ivabradine activity (i.e. 12 ± 1 hours post-dosing) and 24 ± 2 hours after amlodipine or nifedipine administration on centrally read values. ETT will be performed at SEL, W0, and W6 (trough and peak of ivabradine activity) visits and the following parameters will be measured: 1. Total Exercise Duration (TED, sec)* 2. Time to onset of 1 mm ST segment depression (TST 1 mm, sec)* 3. Time to onset of angina pain (TAO, sec)** 4. Time to Limiting Angina (TLA, sec)** 5. Heart Rate at rest and at peak of exercise (HR, bpm)* 6. Rate Pressure Product at rest and at peak of exercise (RPP, bpm x mmHg)* * Evaluated by Core Reading Centre ** Evaluated by investigator |
| Secondary outcome measures | Changes in other classical exercise tolerance test parameters (secondary efficacy criteria): 1. Change over a 6-week treatment period in all the ETT criteria (TED, TST 1mm, TAO, TLA, HR and RPP at rest and at peak exercise): 1.1. At the trough of ivabradine activity (i.e. 12 ± 1 hours post-dosing) and 24 ± 2 hours after nifedipine or amlodipine administration 1.2. At the peak of ivabradine activity (i.e. 3 ± 1 hours post-dosing) and 3 ± 1 hours after nifedipine or amlodipine administration 2. Response to TST 1 mm criterion defined as an increase over a 6-week treatment period in the time to 1 mm ST segment depression of at least 60 sec, at the trough of ivabradine activity (i.e. 12 ± 1 hours post-dosing) and 24 ± 2 hours after amlodipine or nifedipine on centrally read values |
| Overall study start date | 15/12/2007 |
| Overall study end date | 31/01/2013 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Both |
| Target number of participants | 1,240 |
| Total final enrolment | 1277 |
| Participant inclusion criteria | 1. Stable angina pectoris 2. Patients already treated with amlodipine or nifedipine 3. Sinus rhythm: heart rate 60 beats per minute |
| Participant exclusion criteria | Heart rate <60 beats per minute |
| Recruitment start date | 15/12/2007 |
| Recruitment end date | 31/01/2013 |
Locations
Countries of recruitment
- Argentina
- Armenia
- Brazil
- Bulgaria
- Chile
- Estonia
- Hungary
- India
- Korea, South
- Lithuania
- Mexico
- Moldova
- Peru
- Philippines
- Poland
- Romania
- Russian Federation
- Serbia
- Slovakia
- Tunisia
- Ukraine
Study participating centre
Faculty Hospital Ruzinov
Bratislava
SR-82606
Slovakia
SR-82606
Slovakia
Sponsor information
Institut de Recherches Internationales Servier (France)
Industry
Industry
50 rue Carnot
Suresnes
92284
France
| Website | http://www.servier.com/ |
|---|---|
"ROR" |
https://ror.org/034e7c066 |
Funders
Funder type
Industry
Institut de Recherches Internationales Servier (France)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Publication plan: Summary results are published on https://clinicaltrials.servier.com. For interventional Phase III studies ending after the 1st January 2014, the results are/will be published in scientific literature. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available upon request from https://clinicaltrials.servier.com if a Marketing Authorisation has been granted after 1st January 2014. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Basic results | 21/04/2020 | No | No |
Editorial Notes
21/04/2020: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
28/03/2018: Publication plan and IPD sharing statement amended
25/01/2018: Publication plan and IPD sharing statement added.
14/12/2017: results summary added.
