Clinical trial NCT03138603: Metoprolol to Reduce Perioperative Myocardial Injury
Official title: Metoprolol to Reduce Perioperative Myocardial Injury
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Diseases
Keywords: surgery
heart disease
metoprolol
myocardial injury
coronary artery disease
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Washington University School of Medicine
First posted: 2017-05-03
Enrollment: 72
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single-center, double blinded placebo controlled
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

1. Age \>= 50 years
2. Beta-blocker naïve \[30 days prior to surgery\]
3. Previously diagnosed coronary artery disease (CAD), or

   1. History of peripheral vascular disease (PVD), or
   2. Chronic kidney disease (CKD) \[eGFR ≤60ml/min\], or
   3. History of positive stress test or
   4. 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
4. Major non-cardiac, elective surgery under general anesthesia

Exclusion Criteria

Subjects will not be enrolled if any of the following criteria exist:

1. History of stroke, or transient ischemic attack (TIA)
2. Previously diagnosed carotid disease, i.e., either 70% unilateral or 50% bilateral carotid occlusion.
3. Heart rate \<=55bpm
4. Congestive heart failure with New York Heart Association(NYHA) Functional Classification of III-IV or left ventricular heart failure with ejection fraction ≤50%
5. Severe valvular regurgitation
6. Second or third degree atrioventricular (AV) block without pacemaker
7. Active asthma or chronic obstructive pulmonary disease (COPD) with symptoms or resolving symptoms on day of surgery
8. Anemia \[HB\<=9g/dL\]
9. Allergy to beta-blockade drugs
10. Unwilling or unable to give consent for participation
11. Undergoing any carotid endarterectomy, endovascular, endoscopic, superficial, or ambulatory procedures
12. Pregnancy or lactating women
13. Prisoners

Primary outcomes:
measure: Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury
timeFrame: 0-3 days, following surgery
Secondary outcomes:
measure: Effectiveness in Reduction of Major Adverse Cardiac Events (MACE)
timeFrame: 0-3 days, following surgery
measure: Monitor Post-operative Myocardial Ischemia
timeFrame: 0-3 days, following surgery
measure: Number of Stroke Related Events Following Surgery
timeFrame: 0-3 days, following surgery
measure: Number of Participants Having Vasopressor Therapy to Regulate Symptomatic Hypotension
timeFrame: 0-3 days, following surgery
measure: Number of Participant Incidence of Clinically Relevant Bradycardia
timeFrame: 0-3 days, following surgery
measure: Participants Number of Days Spent Post-operative Hospitalization
timeFrame: 0-3 days following surgery
measure: Patient Recovery Progress Events at 30-days Post-operative.
timeFrame: 30-days from surgery
measure: Participant Post-operative Mortality at 1-year Following Surgery
timeFrame: 1-Year from surgery
Other outcomes:
measure: Measured Number of Patient Adverse Events
timeFrame: Post-operatively, 0-3 days, and day-30
Locations:
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: University of Chicago Medicine
name: Peter Nagele, MD
role: PRINCIPAL_INVESTIGATOR
References: