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

• Register: ISRCTN
• Last refreshed on: 4 May 2020
• Main ID: ISRCTN18979472
• Date of registration: 18/07/2008
• Prospective Registration: No
• Primary sponsor: Institut de Recherches Internationales Servier (France)
• Public 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
• 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.
• Date of first enrolment: 15/12/2007
• Target sample size: 1240
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN18979472
• Study type: Interventional
• Study design: Randomised, double-blind, parallel-group ,international, multi-centre study (Treatment)
• Phase: Not Specified

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

Contacts

• Name: Gabriel Kamensky

Key inclusion & exclusion criteria

Inclusion criteria:
1. Stable angina pectoris
2. Patients already treated with amlodipine or nifedipine
3. Sinus rhythm: heart rate 60 beats per minute

Exclusion criteria: Heart rate <60 beats per minute

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Angina pectoris
Circulatory System
Angina pectoris

Intervention(s)

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

Primary Outcome(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

Secondary Outcome(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

Secondary ID(s)

2006-006246-34

CL3-16257-068

Source(s) of Monetary Support

Institut de Recherches Internationales Servier (France)

Ethics review

Status:
Approval date:
Contact:

First Latvian Ethics Committee, 14/09/2007

Results

• Results available: Yes
• Date Completed: 31/01/2013