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Clinical Trials/NCT03138603
NCT03138603
Completed
Phase 3

Metoprolol to Reduce Perioperative Myocardial Injury

University of Chicago2 sites in 1 country72 target enrollmentDecember 1, 2016

Overview

Phase
Phase 3
Intervention
Metoprolol Tartrate
Conditions
Heart Diseases
Sponsor
University of Chicago
Enrollment
72
Locations
2
Primary Endpoint
Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury
Status
Completed
Last Updated
3 months ago

Overview

Brief Summary

The purpose of this research study is to test if a commonly used, FDA-approved medication, called metoprolol, given at the conclusion of anesthesia following surgery, and during postoperative admission, reduces the possibility of heart related complications in patients with coronary artery disease (CAD).

Detailed Description

All enrolled patients will be beta-blocker naïve for at least 30-days prior to their scheduled surgical procedure. Study patients will be randomly assigned to an interventional drug arm (metoprolol tartrate vs placebo-comparator). At the conclusion of anesthesia following the surgical procedure, patients hemodynamically stable and meeting study safety parameters (heart rate greater-than-65; systolic blood pressure greater-than-110) will receive 3-intravenous doses of interventional study drug (metoprolol tartrate 5mg or placebo-comparator), based on previously assigned study arm; then, patients remaining hemodynamically stable will receive an oral dose (25mg metoprolol vs placebo-comparator) approximately every 8-hours for up to 3-days during postoperative hospital admission. From arrival in the preop holding area through up to 72 hours postoperative admission to hospital discharge or end of study treatment (whichever occurs first), patients will be continuously monitored through medical records assessments, Holter monitoring, mobile hemodynamic monitoring (VisiMobile), and in-person daily follow-up visits that include 12-lead ECG, and blood collections for serial cardiac biomarkers for high-sensitivity troponin. Additional study patient postoperative assessment will be performed at 30 days and 1 year after surgery. These can be completed by interview and/or medical record review.

Registry
clinicaltrials.gov
Start Date
December 1, 2016
End Date
August 29, 2023
Last Updated
3 months ago
Study Type
Interventional
Study Design
Parallel
Sex
All

Investigators

Responsible Party
Sponsor

Eligibility Criteria

Inclusion Criteria

  • Age \>= 50 years
  • Beta-blocker naïve \[30 days prior to surgery\]
  • Previously diagnosed coronary artery disease (CAD), or
  • History of peripheral vascular disease (PVD), or
  • Chronic kidney disease (CKD) \[eGFR ≤60ml/min\], or
  • History of positive stress test or
  • At high risk for CAD (must meet at least 2 criteria):
  • i. Age \>= 70 years ii. Hypertension iii. Diabetes requiring oral medication or insulin iv. Current smoker or some days smoker within the past 2 years
  • Major non-cardiac, elective surgery under general anesthesia

Exclusion Criteria

  • Subjects will not be enrolled if any of the following criteria exist:
  • History of stroke, or transient ischemic attack (TIA)
  • Previously diagnosed carotid disease, i.e., either 70% unilateral or 50% bilateral carotid occlusion.
  • Heart rate \<=55bpm
  • Congestive heart failure with New York Heart Association(NYHA) Functional Classification of III-IV or left ventricular heart failure with ejection fraction ≤50%
  • Severe valvular regurgitation
  • Second or third degree atrioventricular (AV) block without pacemaker
  • Active asthma or chronic obstructive pulmonary disease (COPD) with symptoms or resolving symptoms on day of surgery
  • Anemia \[HB\<=9g/dL\]
  • Allergy to beta-blockade drugs

Arms & Interventions

Metoprolol

Metoprolol group, 3-intravenous doses of 5mg metoprolol tartrate (over 15-minutes), and oral dose(s) of 25mg metoprolol approximately every 8 hours postoperatively for up to 3-days (or 72 hrs).

Intervention: Metoprolol Tartrate

Placebo

Placebo comparator group, up-to-three intravenous doses of placebo comparator (over 15-minutes), and oral dose(s) of a placebo comparator approximately every 8 hours postoperatively for up to 3-days (or 72 hrs).

Intervention: Placebo

Outcomes

Primary Outcomes

Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury

Time Frame: 0-3 days, following surgery

Measured effectiveness of post-operative beta-blocker therapy to reduce myocardial injury by monitoring daily biomarkers (High-Sensitivity cardiac Troponin \[HS-cTn\]). Daily post-operative biomarker (hs-cTn) measurements to determine myocardial injury. Myocardial injury is defined as a new hscTn elevation \>99th percentile, or a 50% increase if the baseline hscTn is already elevated \>99th percentile

Secondary Outcomes

  • Effectiveness in Reduction of Major Adverse Cardiac Events (MACE)(0-3 days, following surgery)
  • Monitor Post-operative Myocardial Ischemia(0-3 days, following surgery)
  • Number of Stroke Related Events Following Surgery(0-3 days, following surgery)
  • Number of Participants Having Vasopressor Therapy to Regulate Symptomatic Hypotension(0-3 days, following surgery)
  • Number of Participant Incidence of Clinically Relevant Bradycardia(0-3 days, following surgery)
  • Participants Number of Days Spent Post-operative Hospitalization(0-3 days following surgery)
  • Patient Recovery Progress Events at 30-days Post-operative.(30-days from surgery)
  • Participant Post-operative Mortality at 1-year Following Surgery(1-Year from surgery)

Study Sites (2)

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