Promotion of Coronary Collateral Function by Ivabradine-Induced Bradycardia in Patients With Coronary Artery Disease

NCT01039389 | Completed DMC

• 1 other identifier: 237/2008
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study in patients with chronic stable coronary artery disease treatable by percutaneous coronary intervention (PCI) is to evaluate the long-term efficacy and safety of the orally taken selective I(f)-inhibitor Ivabradine (Procoralan®, Servier Switzerland) with regard to the promotion of collateral growth.

Conditions

Coronary Artery Disease

Keywords

Coronary Artery Disease; Stable; Coronary Collaterals; Therapeutic Collateral Promotion; Arteriogenesis; Bradycardia

Outcome Measures

Primary Outcomes (1)

• Collateral flow index (CFI)

  6 months

Secondary Outcomes (1)

• Myocardial blood flow (MBF) during hyperemia

  6 months

Study Arms (2)

Collateral promotion; PCI after 6 months

EXPERIMENTAL

Drug: Ivabradine; Drug: Placebo

Collateral promotion; PCI at baseline

EXPERIMENTAL

Drug: Ivabradine; Drug: Placebo

Interventions

Ivabradine DRUG

bid administration of 5mg ivabradine (max 7.5mg) aiming to reduce resting heart rate to 60/min

Also known as: Procoralan, I(f)-inhibitor

Collateral promotion; PCI after 6 months; Collateral promotion; PCI at baseline

Placebo DRUG

bid placebo

Also known as: Placebo control

Collateral promotion; PCI after 6 months; Collateral promotion; PCI at baseline

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
• to 3-vessel stable coronary artery disease (CAD)
• At least 1 stenotic lesion suitable for PCI
• No Q-wave myocardial infarction in the area undergoing CFI measurement
• Written informed consent to participate in the study

You may not qualify if:

• Acute coronary syndrome
• CAD treated best by surgical coronary bypass
• Indications for BB treatment (heart failure, arrhythmias, \<3months post-infarct)
• RHR \<60/min without any treatment
• Sick sinus syndrome, sinuatrial block or \>2nd degree atrio-ventricular block
• Atrial fibrillation
• Inherited or acquired long-QT syndrome
• Indwelling pacemaker
• Severe hepatic or renal failure (creatinine clearance \<15ml/min)
• Hypersensitivity against ivabradine or adjuvants
• Pre-menopausal women

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Bern University Hospital

Bern, Switzerland

Location

Related Publications (6)

• Patel SR, Breall JA, Diver DJ, Gersh BJ, Levy AP. Bradycardia is associated with development of coronary collateral vessels in humans. Coron Artery Dis. 2000 Sep;11(6):467-72. doi: 10.1097/00019501-200009000-00004.

  PMID: 10966132 BACKGROUND

• DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64(16):1757-65. doi: 10.2165/00003495-200464160-00003.

  PMID: 15301560 BACKGROUND

• Meier P, Gloekler S, de Marchi SF, Indermuehle A, Rutz T, Traupe T, Steck H, Vogel R, Seiler C. Myocardial salvage through coronary collateral growth by granulocyte colony-stimulating factor in chronic coronary artery disease: a controlled randomized trial. Circulation. 2009 Oct 6;120(14):1355-63. doi: 10.1161/CIRCULATIONAHA.109.866269. Epub 2009 Sep 21.

  PMID: 19770393 BACKGROUND

• Meier P, Gloekler S, Zbinden R, Beckh S, de Marchi SF, Zbinden S, Wustmann K, Billinger M, Vogel R, Cook S, Wenaweser P, Togni M, Windecker S, Meier B, Seiler C. Beneficial effect of recruitable collaterals: a 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements. Circulation. 2007 Aug 28;116(9):975-83. doi: 10.1161/CIRCULATIONAHA.107.703959. Epub 2007 Aug 6.

  PMID: 17679611 BACKGROUND

• Rimoldi SF, Messerli FH, Cerny D, Gloekler S, Traupe T, Laurent S, Seiler C. Selective Heart Rate Reduction With Ivabradine Increases Central Blood Pressure in Stable Coronary Artery Disease. Hypertension. 2016 Jun;67(6):1205-10. doi: 10.1161/HYPERTENSIONAHA.116.07250. Epub 2016 Apr 18.

  PMID: 27091900 DERIVED

• Gloekler S, Traupe T, Stoller M, Schild D, Steck H, Khattab A, Vogel R, Seiler C. The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease. Heart. 2014 Jan;100(2):160-6. doi: 10.1136/heartjnl-2013-304880. Epub 2013 Nov 1.

  PMID: 24186565 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Bradycardia

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Arrhythmias, Cardiac; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Christian Seiler, MD, Prof.

  Insel Gruppe AG, University Hospital Bern

  STUDY CHAIR

• Michael Stoller, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

• Tobias Traupe, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 24, 2009
• First Posted: December 25, 2009
• Study Start: October 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: July 12, 2013

Record last verified: 2013-07

Locations

CH (1)