Study to Investigate the Effect of Heart Rate Reduction With Ivabradine on Vascular Elastic Properties and Endothelial Function in Patients With Stable Coronary Heart Disease
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|ClinicalTrials.gov Identifier: NCT01768585|
Recruitment Status : Unknown
Verified January 2013 by University Hospital, Saarland.
Recruitment status was: Recruiting
First Posted : January 15, 2013
Last Update Posted : January 15, 2013
|Condition or disease||Intervention/treatment||Phase|
|Coronary Artery Disease Coronary Arteriosclerosis||Drug: Ivabradine Drug: Placebo||Phase 4|
Experimental and clinical data suggest that sustained elevation of heart rate contributes to the pathogenesis of vascular disease (1, 2). In animal studies accelerated heart rate is associated with signalling events leading to vascular oxidative stress, endothelial dysfunction and acceleration of atherogenesis (3). The underlying mechanisms are only partially understood and appear to correlate with mechanic properties such as reduction of vascular compliance. Heart rate reduction by I(f)-channel inhibition with ivabradine (Procoralan®, Servier, France) attenuates oxidative stress, improves endothelial function and reduces the formation of atherosclerotic plaques in mice models of lipid-induced atherosclerosis (1, 4).
Aortic stiffness is a consequence of arterial aging and vascular risk factors and determinates cardiovascular mortality (5). Heart rate depending repetitive pulsations appear to induce fatigue and fracture of elastin lamellae of central arteries. As a result the vessel stiffens and pulse wave reflections return earlier to the heart. In consequence aortic pressure rises and pulsations of flow extend further into smaller vessels of organs (notably the brain and kidney). Stiffening leads to increased left ventricular (LV) load with hypertrophy, decreased capacity for myocardial perfusion, and increased hemodynamic stresses on small arterial vessels.
Several experimental investigations revealed an interaction between heart rate and vascular compliance demonstrating a positive association between increased heart rate and arterial stiffness (6). Recent experimental data suggest that heart rate reduction by ivabradine (Procoralan®, Servier, France) significantly improves aortic distensibility in cholesterol fed ApoE -/- mice measured by MRI technique (7). While a benefit of pharmacological heart rate reduction on vascular outcomes was observed in animal studies, prospective clinical data are limited and evidence determining whether chronic modulation of heart rate can improve vascular function and compliance in patients with chronic stable coronary artery disease is needed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomised, Placebo Controlled, Double Blind, Cross-over, Single Center Clinical Study to Investigate the Effect of Heart Rate Reduction With Ivabradine on Vascular Elastic Properties and Endothelial Function in Patients With Stable Coronary Heart Disease|
|Study Start Date :||December 2012|
|Estimated Primary Completion Date :||December 2014|
|Estimated Study Completion Date :||December 2014|
Active Comparator: Ivabradine
Drug: Ivabradine bid administration of 7.5mg ivabradine Other Name: Procoralan, I(f)-inhibitor
Please see description of Intervention Arm
Other Name: Procoralan
Placebo Comparator: Placebo
Drug: Placebo bid placebo Other Name: Placebo control
- Aortic distensibility (MRI), pulse wave velocity (SphygmoCor®), flow-mediated dilatation (A. brachialis) [ Time Frame: Decembre 2014 ]
- Biomarkers (inflammation, oxidative stress) [ Time Frame: Decembre 2014 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01768585
|Contact: Florian Custodis, MD||0049-6841-1623000||Florian.Custodis@uks.eu|
|Contact: Angelika Knoll||0049-6841-23412||Angelika.Knoll@uks.eu|
|University Hospital, Saarland||Recruiting|
|Homburg, Saarland, Germany, 66421|
|Contact: Florian Custodis, MD 0049-6841-1623000 Florian.Custodis@uks.eu|
|Contact: Angelika Knoll 0049-6841-1623412 Angelika.Knoll@uks.eu|
|Principal Investigator: Ulrich Laufs, Prof. Dr.|
|Sub-Investigator: Florian Custodis, MD|
|Principal Investigator:||Ulrich Laufs||Saarland University Hospital|