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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Hospital Universitario de Canarias.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Hospital Universitario de Canarias
ClinicalTrials.gov Identifier:
NCT00815100
First received: December 25, 2008
Last updated: April 5, 2011
Last verified: April 2011
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


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 Comparator: Placebo 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).
Active Comparator: Ivabradine 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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Francisco Bosa-Ojeda, MD, PhD +34 922 678457 franbosa@ull.es

Locations
Spain
Hospital Universitario de Canarias Recruiting
La Laguna, Santa Cruz de Tenerife, Spain, 38320
Contact: Alberto Domínguez Rodríguez, MD,PhD       adrvdg@hotmail.com   
Principal Investigator: Alberto Domínguez Rodríguez, MD, PhD         
Sponsors and Collaborators
Hospital Universitario de Canarias
  More Information

No publications provided

Responsible Party: Francisco Bosa Ojeda, Hospital Universitario de Canarias
ClinicalTrials.gov Identifier: NCT00815100     History of Changes
Other Study ID Numbers: Riviera/09
Study First Received: December 25, 2008
Last Updated: April 5, 2011
Health Authority: Spain: Comité Ético de Investigación Clínica

Keywords provided by Hospital Universitario de Canarias:
Ivabradine
Acute coronary syndrome.
Inflammation
C-reactive protein
Atherosclerosis

Additional relevant MeSH terms:
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on September 29, 2014