Additional identifiers
EudraCT/CTIS number
2006-006246-34
IRAS number
ClinicalTrials.gov number
Protocol/serial number
CL3-16257-068
Study information
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.
Acronym
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
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
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
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
Reason abandoned (if study stopped)
Eligibility
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 type(s)
Patient
Age group
Not Specified
Sex
Both
Target number of participants
1,240
Total final enrolment
1277
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
Sponsor information
Organisation
Institut de Recherches Internationales Servier (France)
Sponsor details
50 rue Carnot
Suresnes
92284
France
Sponsor type
Industry
Website
ROR
Funders
Funder type
Industry
Funder name
Institut de Recherches Internationales Servier (France)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
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.
Intention to publish date
Individual participant data (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.
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | No | No | |||
| Basic results | 21/04/2020 | No | No |