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Coronary Artery DiseaseNCT01039389

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

A study testing Ivabradine in people with Coronary Artery Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Coronary Artery Disease
What is being tested?
Ivabradine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
43 participants
Where
1 siteSwitzerland
Study dates
Oct 2009to Mar 2013
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age > 18 years old
  • 1- 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Switzerland1 site

  • Bern University Hospital

    Bern

Other trials in Switzerland

About this study

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.

Read the detailed description

Coronary artery disease (CAD) is the leading cause of death in industrialized countries. Current therapies for restoration of coronary flow are percutaneous coronary intervention (PCI) or surgical revascularization. However, inherent to them are procedure-related risks and the fact that CAD progression is not prevented. Additionally, up to one fourth of all CAD patients are not amenable to standard revascularization therapies. Thus, there is a need for alternative therapies. Coronary collaterals as natural bypasses are anastomoses without an intervening capillary bed between portions of the same coronary artery or between different coronary arteries. The coronary collateral circulation is prevalent in humans and in CAD the amount of collateral flow is directly related to infarct size, all-cause- and cardiac mortality. Thus, the goal is to promote collateral function in the sense of prophylactic myocardial salvage.

Coronary (collateral) blood flow occurs almost entirely during diastole. Fluid shear stress (FSS) is the driving force in the formation, promotion and maintenance of collaterals (i.e. arteriogenesis). It is the product of blood viscosity and shear rate, the latter being the fluid velocity change between different fluid layers which is related to the fluid velocity at the endothelium. Prolongation of diastole via reduction of resting heart rate (RHR) is naturally equal to extension of shear stress at the endothelium. Bradycardia is likely to be the key factor for augmented collateral function: In several animal models, an inverse relation between heart rate and collateral function was found. We have recently confirmed this finding investigating collateral function measurements in normal coronary arteries of our patient population.

The fact that beta blockers depress contractility and unmask beta-adrenergic coronary vasoconstriction has prompted the development of selective I(f)-inhibitors. To date, ivabradine is the only clinically available specific inhibitor of the pacemaker current in the sinuatrial node (called "funny" current, because of permeability for mixed ions and activation by hyperpolarization instead of depolarization, I(f)). It acts as a pure heart rate lowering agent without affecting blood pressure, myocardial contractility, intra-cardiac conduction, or ventricular repolarization. In contrast to beta blockers or calcium channel blockers, it mimics physiological bradycardia and is therefore appropriate for the purpose of this study. By bradycardization in CAD, ischemia is targeted via reduction of myocardial oxygen demand and increase of oxygen supply without negative inotropic, coronary vasoconstrictive, or metabolic effects. In terms of anti-anginal efficacy, ivabradine has been found to be as effective as atenolol or amlodipine.

Being tested
Ivabradine, Placebo
Keywords
Coronary Artery Disease, Stable, Coronary Collaterals, Therapeutic Collateral Promotion, Arteriogenesis, Bradycardia
Medical subject headings
Coronary Artery Disease, Bradycardia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvabradineDrug

    Also called Procoralan, I(f)-inhibitor

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

  • PlaceboDrug

    Also called Placebo control

    bid placebo

Study groups in NCT01039389
Study groupRoleWhat they receive
Collateral promotion; PCI after 6 monthsExperimentalNot described
Receives: Drug: Ivabradine; Drug: Placebo
Collateral promotion; PCI at baselineExperimentalNot described
Receives: Drug: Ivabradine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Collateral flow index (CFI)

    Measured: 6 months

Secondary outcomes (1)

  1. Myocardial blood flow (MBF) during hyperemia

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Dec 2009 (estimated)
  2. Study startOct 2009
  3. Primary completionMar 2013
  4. Study completionMar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01039389
Sponsor's protocol ID
237/2008
Status last verified
Jul 2013
First submitted
24 Dec 2009
Last updated
12 Jul 2013
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 10966132

  • 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.

    PubMed 15301560

  • 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.

    PubMed 19770393

  • 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.

    PubMed 17679611

  • 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.

    PubMed 27091900

  • 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.

    PubMed 24186565

Questions about this trial

What is this clinical trial studying?

A study testing Ivabradine in people with Coronary Artery Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Collateral flow index (CFI) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01039389, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2013.

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