Metoprolol to Reduce Perioperative Myocardial Injury (ORION)

The University of Chicago

Status and phase: Completed; Phase 3

Conditions: Heart Diseases

Treatments: Drug: Placebo; Drug: Metoprolol Tartrate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03138603

5R01HL126892 (U.S. NIH Grant/Contract)

IRB19-1797

Details and patient eligibility

About

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).

Full 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.

Enrollment: 72 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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72 participants in 2 patient groups, including a placebo group

Metoprolol

Experimental group

Description:

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).

Treatment:

Drug: Metoprolol Tartrate

Placebo

Placebo Comparator group

Description:

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).

Treatment:

Drug: Placebo