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

NCT ID: NCT00815100

Last Updated: 2020-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-09-07

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.

Conditions

Acute Coronary Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Ivabradine

Group Type: ACTIVE_COMPARATOR

Ivabradine

Intervention Type: DRUG

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).

Interventions

Ivabradine

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

Placebo

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

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario de Canarias

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, Spain

Countries

Spain

Other Identifiers

Riviera/09

Identifier Type: -

Identifier Source: org_study_id