Official Title: “Use of Prophylactic Beta Blockade to Prevent Peri-Extubation Cardiac Ischemia and Congestive Heart Failure”

Silent myocardial ischemia is known to occur in the general medical intensive care unit population immediately following tracheal extubation. We believe these patients are at risk for primary cardiac events in the 4 hours immediately following extubation. Metoprolol is a selective beta-1 antagonist, with little to no beta-2 activity at low and moderate doses. The cardioprotective effects of beta blockade have been well documented in randomized controlled trials. In patients undergoing extubation, prophylactic use of intravenous metoprolol may reduce post-extubation ischemia events as well as precursors of cardiogenic pulmonary edema (atrial and ventricular wall tension). Our primary hypothesis is that prophylactic metoprolol (titrated to reduce resting heart rate by at least 10%) prior to tracheal extubation will reduce the rate of ischemia as judged by ST segment analysis.

Study Type: Interventional

Study Design: Prevention, Randomized, Single Blind (Outcomes Assessor), Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Drug: Metoprolol
  • Metoprolol administered intravenously in 2.5mg boluses until the resting heart rate falls by 10% from baseline to a maximum dose of 10mg, or until there is any apparent adverse reaction.

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: Control
• Active Comparator: Metoprolol

Primary Measures

• The rate of ischemia as judged by ST segment analysis in the 4h following extubation
  • Time Frame: 4 hours
    Safety Issue?: No

Secondary Measures

• Rate-pressure product following extubation
  • Time Frame: 30min, 2h, 4h
    Safety Issue?: No
• Troponin T elevations, the incidence of cardiogenic edema, and the rate of reintubation
  • Time Frame: 48h
    Safety Issue?: No
• Pro-BNP levels
  • Time Frame: 30min
    Safety Issue?: No

Inclusion Criteria:

• Adult medical or cardiac intensive care unit patients on mechanical ventilation who have known coronary artery disease or have at least 2 of the following risk factors for coronary artery disease:
• Cigarette smoking
• Hypertension (BP 140/90 or antihypertensive medication)
• Low HDL-cholesterol (HDL-C) (<40 mg/dL [1.03 mmol/L])
• Family history of premature CHD (in male first degree relatives <55 years, in female first degree relative <65 years)
• Age (men 45 years, women 55 years)
• Diabetes mellitus
• Symptomatic carotid artery disease
• Peripheral arterial disease
• Abdominal aortic aneurysm

Exclusion Criteria:

• Arterial hypotension, defined as mean arterial pressure < 60 mmHg or requiring any intravenous vasoactive medication.
• The presence of known reactive airway disease.
• Resting heart rate of <60 in the period prior to tracheal extubation..
• The presence of decompensated congestive heart failure, defined as requiring continuous infusion of an inotropic agent.
• Known hypersensitivity to beta-blockers or any other contraindication to their use.
• Subjects younger than 18 years of age.
• Inability to obtain consent from the subject or the subjects authorized representative.
• Pregnancy
• Digoxin therapy
• Current therapy with a beta-blocker

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Iowa

Overall Clinical Trial Officials and Contacts

Gregory A Schmidt, MD Principal Investigator University of Iowa  

Overall Contact: Gregory A Schmidt, MD 3193846746 gregory-a-schmidt@uiowa.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00563238

Study ID Number: 200708711

ClinicalTrials.gov Identifier: NCT00563238

Health Authority: United States: Institutional Review Board