Metoprolol to Reduce Perioperative Myocardial Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Metoprolol to Reduce Perioperative Myocardial Injury

Conditions
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Heart Diseases

Intervention / Treatment
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* Drug: Metoprolol Tartrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 Unwilling or unable to give consent for participation Undergoing any carotid endarterectomy, endovascular, endoscopic, superficial, or ambulatory procedures Pregnancy or lactating women Prisoners

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center, double blinded placebo controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metoprolol<br>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). | Drug: Metoprolol Tartrate<br>* Patients will be randomly assigned to receive up-to-three intravenous doses of 5mg metoprolol tartrate (over 15-minutes) at the end of their surgical procedure, and a scheduled oral dose regimen of 25mg metoprolol approximately every 8-hours postoperatively for up to 3-days (or 72 hrs).<br>* Other names: Beta-blocker;|
| Placebo Comparator: Placebo<br>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). | Drug: Placebo<br>* Patients will be randomly assigned to receive up-to-three intravenous doses of a placebo-comparator (over 15-minutes) at the end of their surgical procedure, and scheduled oral dose regimen of a placebo-comparator approximately every 8-hours postoperatively for up to 3-days (or 72 hrs).<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of Myocardial Injury following Post-op Beta-blocker therapy | Measure effectiveness of post-operative beta-blocker therapy to reduce myocardial injury by monitoring daily biomarkers (High-Sensitivity cardiac Troponin [HS-cTn]). Myocardial injury is defined as a new hscTn elevation >99th percentile, or a 50% increase if the baseline hscTn is already elevated >99th percentile | Up to 72 hours following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in Major Adverse Cardiac Events (MACE) | MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization | Up to 72 hours following surgery | 
| Monitor Post-operative Myocardial ischemia | Post-operative cardiac monitoring via ECG to evaluate if myocardial ischemia is present. Myocardial Ischemia is defined as ST depression or elevation of ≥0.2 mV in one lead or ≥0.1 mV in two contiguous leads lasting ≥10 min | Up to 72 hours following surgery | 
| Stroke related events following surgery | Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset | Up to 72 hours following surgery | 
| Vasopressor Therapy to Regulate Symptomatic Hypotension | Monitor vasopressor requirements for blood pressure regulation due to symptomatic hypotension. Symptomatic hypotension (systolic BP < 90 mmHg) can be determined by clinical intervention due to low blood pressure and/or patient developed clinical symptoms due to hypotension. | Up to 72 hours following surgery | 
| Incidence of Clinically Relevant Bradycardia | Monitor cumulative events of bradycardia rate/duration time. Bradycardia is defined as low heart rate (HR < 50/min). | Up to 72 hours following surgery | 
| Length of Post-operative Hospitalization | Measure post-operative length of admission associated with level of care until discharge (regular floor, intensive care unit, observation unit). | Up to 72 hours following surgery | 
| Recovery Progress 30-day Post-operative | Monitor post-operative recovery 30-days following the procedure to determine if changes to medications, readmissions, or other events have occurred since hospital discharge. | 30-days from surgery | 
| Post-operative Mortality at 1-year | Collect 1-year post-operative mortality of study population. Measured by 'living', 'deceased', 'date of death'. | 1-Year from surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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surgery, heart disease, metoprolol, myocardial injury, coronary artery disease