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Metoprolol to Reduce Perioperative Myocardial Injury (ORION)

Primary Purpose

Heart Diseases

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metoprolol Tartrate
Placebo
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Diseases focused on measuring surgery, heart disease, metoprolol, myocardial injury, coronary artery disease

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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

    1. History of PVD, or
    2. 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 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 AV block without pacemaker
  7. Active asthma or 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

Sites / Locations

  • University of Chicago Medicine
  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Metoprolol

Placebo

Arm 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).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Reduction in Major Adverse Cardiac Events (MACE)
MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization
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
Stroke related events following surgery
Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset
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.
Incidence of Clinically Relevant Bradycardia
Monitor cumulative events of bradycardia rate/duration time. Bradycardia is defined as low heart rate (HR < 50/min).
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).
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.
Post-operative Mortality at 1-year
Collect 1-year post-operative mortality of study population. Measured by 'living', 'deceased', 'date of death'.

Full Information

First Posted
April 26, 2017
Last Updated
October 17, 2023
Sponsor
University of Chicago
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03138603
Brief Title
Metoprolol to Reduce Perioperative Myocardial Injury
Acronym
ORION
Official Title
Metoprolol to Reduce Perioperative Myocardial Injury
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
April 18, 2023 (Actual)
Study Completion Date
August 29, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
Collaborators
National Heart, Lung, and Blood Institute (NHLBI), Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Diseases
Keywords
surgery, heart disease, metoprolol, myocardial injury, coronary artery disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Single-center, double blinded placebo controlled
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double blind masking
Allocation
Randomized
Enrollment
170 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metoprolol
Arm Type
Experimental
Arm 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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Metoprolol Tartrate
Other Intervention Name(s)
Beta-blocker
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sham, Placebo-comparator, Control
Intervention Description
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).
Primary Outcome Measure Information:
Title
Reduction of Myocardial Injury following Post-op Beta-blocker therapy
Description
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
Time Frame
Up to 72 hours following surgery
Secondary Outcome Measure Information:
Title
Reduction in Major Adverse Cardiac Events (MACE)
Description
MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization
Time Frame
Up to 72 hours following surgery
Title
Monitor Post-operative Myocardial ischemia
Description
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
Time Frame
Up to 72 hours following surgery
Title
Stroke related events following surgery
Description
Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset
Time Frame
Up to 72 hours following surgery
Title
Vasopressor Therapy to Regulate Symptomatic Hypotension
Description
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.
Time Frame
Up to 72 hours following surgery
Title
Incidence of Clinically Relevant Bradycardia
Description
Monitor cumulative events of bradycardia rate/duration time. Bradycardia is defined as low heart rate (HR < 50/min).
Time Frame
Up to 72 hours following surgery
Title
Length of Post-operative Hospitalization
Description
Measure post-operative length of admission associated with level of care until discharge (regular floor, intensive care unit, observation unit).
Time Frame
Up to 72 hours following surgery
Title
Recovery Progress 30-day Post-operative
Description
Monitor post-operative recovery 30-days following the procedure to determine if changes to medications, readmissions, or other events have occurred since hospital discharge.
Time Frame
30-days from surgery
Title
Post-operative Mortality at 1-year
Description
Collect 1-year post-operative mortality of study population. Measured by 'living', 'deceased', 'date of death'.
Time Frame
1-Year from surgery
Other Pre-specified Outcome Measures:
Title
Adverse Events
Description
Monitor adverse events and severity associated with low blood pressure (hypotension), low heart heart (bradycardia), nausea and vomiting; or other symptoms determined 'probably', 'possibly', 'unrelated', or 'related' to the study intervention. This includes any unplanned escalation of care admissions (e.g., Intensive Care Unit [ICU]). Study patient safety is monitored by the investigators (MD) with experience in critical care anesthesia, as well as an experienced clinical research team responsible for data collection and reporting of events.
Time Frame
Length of participation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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 Unwilling or unable to give consent for participation Undergoing any carotid endarterectomy, endovascular, endoscopic, superficial, or ambulatory procedures Pregnancy or lactating women Prisoners
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Nagele, MD
Organizational Affiliation
University of Chicago Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Metoprolol to Reduce Perioperative Myocardial Injury

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