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

NCT01768585 | Unknown Phase 4

• 1 other identifier: HomRate04_2012
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates whether chronic heart rate reduction with ivabradine (Procoralan®, Servier, France) affects aortic compliance and endothelial function in patients with chronic stable coronary artery disease.

Conditions

Coronary Artery Disease; Coronary Arteriosclerosis

Outcome Measures

Primary Outcomes (1)

• Aortic distensibility (MRI), pulse wave velocity (SphygmoCor®), flow-mediated dilatation (A. brachialis)

  Decembre 2014

Secondary Outcomes (1)

• Biomarkers (inflammation, oxidative stress)

  Decembre 2014

Study Arms (2)

Ivabradine

ACTIVE COMPARATOR

Drug: Ivabradine bid administration of 7.5mg ivabradine Other Name: Procoralan, I(f)-inhibitor

Drug: Ivabradine

Placebo

PLACEBO COMPARATOR

Drug: Placebo bid placebo Other Name: Placebo control

Drug: Placebo

Interventions

Ivabradine DRUG

Please see description of Intervention Arm

Also known as: Procoralan

Ivabradine

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years old
• Resting heart rate ≥ 70 bpm
• Sinus rhythm
• Chronic stable coronary artery disease (CAD)
• Coronary artery disease proven by coronary angiography
• Written informed consent to participate in the study

You may not qualify if:

• Acute coronary syndrome
• CAD treated best by surgical coronary bypass
• Stroke/TIA
• Resting heart rate \< 70 bpm
• Indwelling pacemaker or AICD
• Severe valvular heart disease
• Any other rhythm than sinus
• Sick-Sinus-Syndrome, SA nodal block, \>2nd degree atrio-ventricular block
• Untreated arterial hypertension
• Arterial hypotension (\<90/50mmHg)
• Severe hepatic failure
• Heart failure (NYHA class III - IV)
• Patient already treated with study drug
• Symptomatic PAD
• Known diabetes mellitus

Sponsors & Collaborators

• University Hospital, Saarland: lead
• Universität des Saarlandes: collaborator

Study Sites (1)

University Hospital, Saarland

Homburg, Saarland, 66421, Germany

RECRUITING

Related Publications (7)

• Custodis F, Baumhakel M, Schlimmer N, List F, Gensch C, Bohm M, Laufs U. Heart rate reduction by ivabradine reduces oxidative stress, improves endothelial function, and prevents atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2008 May 6;117(18):2377-87. doi: 10.1161/CIRCULATIONAHA.107.746537. Epub 2008 Apr 28.

  PMID: 18443241 BACKGROUND

• Beere PA, Glagov S, Zarins CK. Retarding effect of lowered heart rate on coronary atherosclerosis. Science. 1984 Oct 12;226(4671):180-2. doi: 10.1126/science.6484569.

  PMID: 6484569 BACKGROUND

• Custodis F, Schirmer SH, Baumhakel M, Heusch G, Bohm M, Laufs U. Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol. 2010 Dec 7;56(24):1973-83. doi: 10.1016/j.jacc.2010.09.014.

  PMID: 21126638 BACKGROUND

• Noels H, Weber C. Fractalkine as an important target of aspirin in the prevention of atherogenesis : Editorial to: "Aspirin inhibits fractalkine expression in atherosclerotic plaques and reduces atherosclerosis in ApoE gene knockout mice" by H. Liu et al. Cardiovasc Drugs Ther. 2010 Feb;24(1):1-3. doi: 10.1007/s10557-009-6213-4. No abstract available.

  PMID: 20033269 BACKGROUND

• Cavalcante JL, Lima JA, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011 Apr 5;57(14):1511-22. doi: 10.1016/j.jacc.2010.12.017.

  PMID: 21453829 BACKGROUND

• Mangoni AA, Mircoli L, Giannattasio C, Ferrari AU, Mancia G. Heart rate-dependence of arterial distensibility in vivo. J Hypertens. 1996 Jul;14(7):897-901. doi: 10.1097/00004872-199607000-00013.

  PMID: 8818929 BACKGROUND

• Custodis F, Fries P, Muller A, Stamm C, Grube M, Kroemer HK, Bohm M, Laufs U. Heart rate reduction by ivabradine improves aortic compliance in apolipoprotein E-deficient mice. J Vasc Res. 2012;49(5):432-40. doi: 10.1159/000339547. Epub 2012 Jul 3.

  PMID: 22759927 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ulrich Laufs

  Saarland University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Florian Custodis, MD

CONTACT

0049-6841-1623000; Florian.Custodis@uks.eu

Angelika Knoll

CONTACT

0049-6841-23412; Angelika.Knoll@uks.eu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: January 15, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 15, 2013

Record last verified: 2013-01

Locations

DE (1)