Effects of oral chronic administration of ivabradine (7.5 mg bid) in comparison to placebo (bid) on top of beta-blockers, on central aortic blood pressure. Randomized, cross-over, double blind, multicentre, study over 10 weeks in patients with stable coronary artery disease and a resting heart rate equal or superior to 70 bpm, already treated with beta-blockers.
- Conditions
- Coronary Artery DiseaseMedDRA version: 16.0Level: PTClassification code 10011078Term: Coronary artery diseaseSystem Organ Class: 10007541 - Cardiac disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2011-004779-35-IT
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
- Male or female patients, at least 30 years old at the date of selection,
- Patients with CAD documented,
- Patients in sinus rhythm and with HR= 70 bpm on 12-lead ECG after 5 minutes rest,
- Patients with brachial SBP/DBP =140/90 mmHg (mean of 3 measurements performed in supine position using a semi-automatic oscillometric device at 5 min intervals),
- Normal (considering the patient disease) fasting lab test results for sampling performed between selection and inclusion visits,
- Patients with stable and appropriate treatment (according to the investigator) with beta-blockers (at the exception of nebivolol and carvedilol), during at least 3 months before the selection visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
- Known severe renal disease, including renal failure or serum creatinine = 200 µM or µmol/L or 2.2 mg/dL,
- Known moderate or severe hepatic disease including severe hepatic insufficiency and/ or severe liver function test abnormalities: ALT or AST > 3 times the upper reference limits,
- Significant anaemia defined as blood hemoglobin lower than 110 g/L (in males) or lower than 100 g/L (in females),
- Fasting glucose > 13 mmol/L,
- History of central neuropathy and/or of symptomatic orthostatic hypotension,
- Severe hypotension at the time of selection (blood pressure < 90 / 50 mmHg),
- Patient currently or previously treated with ivabradine within the last 3 months before selection visit,
- Patient currently or previously treated with nebivolol or carvedilol within the last 3 months before selection visit,
- Patients with recent (less than 3 months) MI or coronary revascularisation,
- Patients with recent (less than 3 months) stroke or cerebral transient ischemic attack,
- Patients scheduled for coronary revascularisation procedures (PCI or CABG)
- Patients with Type I diabetes
- Type II diabetes patients diagnosed less than 3 month before selection
- Type II diabetes patients with modification of their anti-diabetic medications within 3 months before selection
- Modification of the anti-diabetic treatment since selection visit for diabetic patients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of ivabradine on central aortic systolic blood pressure (CASBP) in comparison to placebo in patients with stable CAD and a resting HR= 70 bpm, treated by beta-blockers.;Secondary Objective: To investigate the effect of ivabradine in comparison to placebo on:<br>- other central and radial blood pressure and heart rate parameters obtained through applanation tonometry,<br>- carotid-femoral pulse wave velocity (PWV),<br>- skin capillary density (only in patients from centres equipped with intravital video capillaroscopy material),<br>- brachial blood pressure parameters,<br>- resting HR from 12-lead Electrocardiogram (ECG),<br>- safety.<br>;Primary end point(s): Central aortic systolic blood pressure (CASBP);Timepoint(s) of evaluation of this end point: Measured at baseline and after 3weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Other central pressure parameters: Central aortic diastolic blood pressure (CADBP), augmentation index (AIx), augmentation pressure (Ao), aortic pulse pressure (PP), subendocardial viability ratio (SEVR) (Buckberg index), LV ejection time (LVET), <br>- Radial blood pressure parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), radial pulse pressure (PP)<br>- Heart rate derived from applanation tonometry during recording of central pressure parameters <br>- Carotid-femoral pulse wave velocity (PWV) <br>- Capillary density<br>- Resting HR from 12 lead ECG<br>- Supine brachial blood pressure parameters (SBP, DBP),<br>- Safety profile ;Timepoint(s) of evaluation of this end point: - resting HR from ECG : at baseline,<br>- safety profile : over all the sudy period,<br>- other secondary endpoints : measured at baseline and after 3 weeks of treatment