Effects of the Ivabradine on Reduction of Inflammatory Markers in Patients With Acute Coronary Syndrome - Full Text View

Sponsored by:	Hospital Universitario de Canarias
Information provided by:	Hospital Universitario de Canarias
ClinicalTrials.gov Identifier:	NCT00815100

Purpose

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

Condition	Intervention	Phase
Acute Coronary Syndromes	Drug: Ivabradine Drug: Placebo	Phase IV

Drug Information available for: S 16257

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Hospital Universitario de Canarias:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

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. [ Time Frame: day 30, 90, 180 and 360 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1270
Study Start Date:	April 2009
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo: Placebo Comparator	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).
Ivabradine: Active Comparator	Drug: 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).

Arms

Assigned Interventions

Placebo: Placebo Comparator

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).

Ivabradine: Active Comparator

Drug: 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).

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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:
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.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815100

Contacts

Contact: Francisco Bosa-Ojeda, MD, PhD

+34 922 678457

franbosa@ull.es

Sponsors and Collaborators

Hospital Universitario de Canarias

More Information

Responsible Party:	Hospital Universitario de Canarias ( Francisco Bosa Ojeda )
Study ID Numbers:	Riviera/09
Study First Received:	December 25, 2008
Last Updated:	December 26, 2008
ClinicalTrials.gov Identifier:	NCT00815100
Health Authority:	Spain: Comité Ético de Investigación Clínica

Keywords provided by Hospital Universitario de Canarias:

Ivabradine
Acute coronary syndrome.
Inflammation
C-reactive protein
Atherosclerosis

Study placed in the following topic categories:

Atherosclerosis
Heart Diseases
Myocardial Ischemia
Acute Coronary Syndrome

Vascular Diseases
Ischemia
Inflammation

Additional relevant MeSH terms:

Pathologic Processes
Disease
Syndrome
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 13, 2009