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Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome

Primary Purpose

Acute Coronary Syndromes

Status
Completed
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Ivabradine
Placebo
Sponsored by
Hospital Universitario de Canarias
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndromes focused on measuring Ivabradine, Acute coronary syndrome., Inflammation, C-reactive protein, Atherosclerosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female.
  2. Age > 18 years.

  3. Ischemic symptoms suspected to represent a non-ST segment elevation acute coronary syndrome defined as:

    Clinical history consistent with new onset, or a worsening pattern, of characteristic ischemic chest pain occuring at rest or with minimal exertion (lasting longer than 10 min) and planned to be managed with an early invasive strategy with intention to perform a percutaneous coronary intervention as early as possible and not later than 72 hours of randomization, and at least one of the following:

    1. ECG changes compatible with new ischemia (ST depression of at least 1 mm or transient ST elevation or ST elevation of <1 mm or T wave inversion >3 mm in at least 2 contiguous leads; or
    2. Already elevated cardiac enzymes (eg, CK-MB) or biomarkers (troponin I or T) above the upper limit of normal.
  4. Patients should be in sinus rhythm with a resting HR of > 60 beats per minute on a resting standard 12-lead ECG.
  5. Written informed consent obtained.

Exclusion Criteria:

  1. Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent.
  2. Pregnant or breast-feeding women or women of childbearing potential.
  3. Patients with recent (< 6 months) myocardial infarction or coronary revascularization or with a history of stroke or cerebral transient ischemic attack within the preceding 3 months or scheduled for revascularization (percutaneous coronary intervention and coronary artery bypass graft).

  4. Patients with at least 1 of the following criteria:

    • Implanted pacemaker or implantable cardioverter defibrillator.
    • Valvular disease likely to require surgery within the next 2 years.
    • Sick sinus syndrome, sinoatrial block, congenital long QT syndrome, complete atrioventricular block.
    • Expectation of death from other illness during the course of the trial.
    • Known severe liver or renal disease.
    • Requiring or likely to require the following medications: macrolide antibiotics, cyclosporin, gestodene, antiretroviral drugs or azole antifungals such as ketoconazole or with known hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
  5. Patients with systemic or cardiac inflammatory processes with the exception of atherosclerosis.

Sites / Locations

  • Hospital Universitario de Canarias

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Ivabradine

Arm Description

Outcomes

Primary Outcome Measures

Whether initiation of ivabradine therapy in patients with acute coronary syndromes immediately after hospital admission decreases high-sensitivity C-reactive protein.

Secondary Outcome Measures

Whether initiation of ivabradine therapy decreases the occurrence of ischemic events (death, nonfatal myocardial infarction, unstable angina, urgent revascularization, cardiac arrest) in patients with acute coronary syndromes.

Full Information

First Posted
December 25, 2008
Last Updated
August 7, 2020
Sponsor
Hospital Universitario de Canarias
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1. Study Identification

Unique Protocol Identification Number
NCT00815100
Brief Title
Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome
Official Title
Randomised, Double-blind, Placebo-controlled Trial of IVabradine in Patients With Acute Coronary Syndrome: Effects of the If Current Inhibitor Ivabradine or rEduction of Inflammation maRkers in Patients With Acute Coronary Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
April 2009 (Actual)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
September 7, 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Universitario de Canarias

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to investigate whether a pure heart rate-lowering agent (Ivabradine) reduces vascular inflammatory stress in patients with acute coronary syndromes
Detailed Description
The activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture, which can lead to the development of acute coronary syndromes. Elevated levels of serum inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) represent independent risk factors for further cardiovascular events. Raised resting heart rate (HR) has been shown to be associated with cardiovascular events. Ivabradine is a new HR-reducing agent, which has demonstrated antianginal and anti-ischemic properties in patients with stable angina. In an atherosclerosis model, selective HR reduction with ivabradine has been shown to decrease markers of vascular oxidative stress, to improve endothelial function, and to reduce atherosclerotic plaque formation. We hypothesized that the addition of ivabradine to standard medical therapy has a beneficial effect on markers of inflammatory stress in acute coronary syndrome patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndromes
Keywords
Ivabradine, Acute coronary syndrome., Inflammation, C-reactive protein, Atherosclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
27 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Ivabradine
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Ivabradine
Intervention Description
Eligible patients will be randomized to 1 of the 2 treatment arms, namely, double-blind ivabradine, or placebo, after hospital admission (at 48 hours). The starting dose of ivabradine will be 5 mg (or matching placebo) twice daily in all patients. Patients receiving 5 mg twice daily (or matching placebo) 1 week after the inclusion with a resting HR of ≥60 beats per minute will receive the target dose of 7.5 mg twice daily (or matching placebo).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Eligible patients will be randomized to 1 of the 2 treatment arms, namely, double-blind ivabradine, or placebo, after hospital admission (at 48 hours). The starting dose of ivabradine will be 5 mg (or matching placebo) twice daily in all patients. Patients receiving 5 mg twice daily (or matching placebo) 1 week after the inclusion with a resting HR of ≥60 beats per minute will receive the target dose of 7.5 mg twice daily (or matching placebo).
Primary Outcome Measure Information:
Title
Whether initiation of ivabradine therapy in patients with acute coronary syndromes immediately after hospital admission decreases high-sensitivity C-reactive protein.
Time Frame
day 4 and day 30
Secondary Outcome Measure Information:
Title
Whether initiation of ivabradine therapy decreases the occurrence of ischemic events (death, nonfatal myocardial infarction, unstable angina, urgent revascularization, cardiac arrest) in patients with acute coronary syndromes.
Time Frame
day 30, 90, 180 and 360

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female. Age > 18 years. Ischemic symptoms suspected to represent a non-ST segment elevation acute coronary syndrome defined as: Clinical history consistent with new onset, or a worsening pattern, of characteristic ischemic chest pain occuring at rest or with minimal exertion (lasting longer than 10 min) and planned to be managed with an early invasive strategy with intention to perform a percutaneous coronary intervention as early as possible and not later than 72 hours of randomization, and at least one of the following: ECG changes compatible with new ischemia (ST depression of at least 1 mm or transient ST elevation or ST elevation of <1 mm or T wave inversion >3 mm in at least 2 contiguous leads; or Already elevated cardiac enzymes (eg, CK-MB) or biomarkers (troponin I or T) above the upper limit of normal. Patients should be in sinus rhythm with a resting HR of > 60 beats per minute on a resting standard 12-lead ECG. Written informed consent obtained. Exclusion Criteria: Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent. Pregnant or breast-feeding women or women of childbearing potential. Patients with recent (< 6 months) myocardial infarction or coronary revascularization or with a history of stroke or cerebral transient ischemic attack within the preceding 3 months or scheduled for revascularization (percutaneous coronary intervention and coronary artery bypass graft). Patients with at least 1 of the following criteria: Implanted pacemaker or implantable cardioverter defibrillator. Valvular disease likely to require surgery within the next 2 years. Sick sinus syndrome, sinoatrial block, congenital long QT syndrome, complete atrioventricular block. Expectation of death from other illness during the course of the trial. Known severe liver or renal disease. Requiring or likely to require the following medications: macrolide antibiotics, cyclosporin, gestodene, antiretroviral drugs or azole antifungals such as ketoconazole or with known hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. Patients with systemic or cardiac inflammatory processes with the exception of atherosclerosis.
Facility Information:
Facility Name
Hospital Universitario de Canarias
City
La Laguna
State/Province
Santa Cruz De Tenerife
ZIP/Postal Code
38320
Country
Spain

12. IPD Sharing Statement

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Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome

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