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
Clinical Trials Information System (CTIS) 2006-006246-34
Protocol serial number CL3-16257-068
Sponsor Institut de Recherches Internationales Servier (France)
Funder Institut de Recherches Internationales Servier (France)
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 of protocol

Not provided at time of registration and not expected to be available in the future

Contact information

Prof Gabriel Kamensky
Scientific

Faculty Hospital Ruzinov
Department of Non-Invasive Cardiology
Ruzinovska 6
Bratislava
SR-82606
Slovakia

Study information

Primary study designInterventional
Study designRandomised, double-blind, parallel-group ,international, multi-centre study
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleEvaluation 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 objectivesTo 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
Health condition(s) or problem(s) studiedAngina pectoris
InterventionAll 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 typeOther
Primary outcome measure(s)

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

Key secondary outcome measure(s)

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

Completion date31/01/2013

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexAll
Target sample size at registration1240
Total final enrolment1277
Key inclusion criteria1. Stable angina pectoris
2. Patients already treated with amlodipine or nifedipine
3. Sinus rhythm: heart rate 60 beats per minute
Key exclusion criteriaHeart rate <60 beats per minute
Date of first enrolment15/12/2007
Date of final enrolment31/01/2013

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

Results and Publications

Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
IPD sharing planThe 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
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes

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.

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