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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01HL126892 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Washington University School of Medicine | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Metoprolol | Experimental | 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 | Placebo Comparator | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Metoprolol Tartrate | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury | 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 | 0-3 days, following surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Effectiveness in Reduction of Major Adverse Cardiac Events (MACE) | MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization | 0-3 days, following surgery |
| Monitor Post-operative Myocardial Ischemia |
| Measure | Description | Time Frame |
|---|---|---|
| Measured Number of Patient Adverse Events | Number of measured participant 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. |
Inclusion Criteria
Age >= 50 years
Beta-blocker naïve [30 days prior to surgery]
Previously diagnosed coronary artery disease (CAD), or
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:
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| Name | Affiliation | Role |
|---|---|---|
| Peter Nagele, MD | University of Chicago Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medicine | Chicago | Illinois | 60637 | United States | ||
| Washington University School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41105735 | Derived | Nagele P, Helwani MA, Samaha E, Kokofer A, Brown F, Karrison T, Gage BF, Brown-Shpigel JC, Rubin DS. A Combined Intravenous and Oral Metoprolol Regimen to Reduce Perioperative Myocardial Injury: The ORION Trial. Anesth Analg. 2026 May 1;142(5):1009-1012. doi: 10.1213/ANE.0000000000007789. Epub 2026 Apr 14. No abstract available. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). Metoprolol Tartrate: 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). |
| FG001 | 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). Placebo: 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). Metoprolol Tartrate: 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury | 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 | Analysis is comprised of participants meeting criteria for randomization to receive intervention, with biomarker (hs-cTn) showing increased value(s). | Posted | Number | participants | 0-3 days, following surgery |
|
Adverse events (AEs) were collected and assessed during study phase participation, e.g., intervention administration, and daily post-operative follow-up, up to 30-days post-operative.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). Metoprolol Tartrate: 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). Post-operative analysis to determine Myocardial Injury (hs-cTnT) in randomized metoprolol group. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| MACE events | Cardiac disorders | Non-systematic Assessment | a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death (e.g., Myocardial Infarction, Cardiac arrest, Stroke.) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia Event | Cardiac disorders | Non-systematic Assessment | A recorded period when heart rate was below 60-beats per minute. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Peter Nagele, MD, MSc | University of Chicago Medicine | 773-795-3544 | pnagele@uchicagomedicine.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 28, 2020 | May 1, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D001161 | Arteriosclerosis |
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| ID | Term |
|---|---|
| D008790 | Metoprolol |
| D000319 | Adrenergic beta-Antagonists |
| C005703 | salicylhydroxamic acid |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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Single-center, double blinded placebo controlled
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Double blind masking
|
|
| Placebo | Drug | 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). |
|
|
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
| 0-3 days, following surgery |
| Number of Stroke Related Events Following Surgery | Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset | 0-3 days, following surgery |
| Number of Participants Having Vasopressor Therapy to Regulate Symptomatic Hypotension | Monitor participants with vasopressor requirements for blood pressure regulation due to symptomatic hypotension (rate/duration time). 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. | 0-3 days, following surgery |
| Number of Participant Incidence of Clinically Relevant Bradycardia | Monitored participants with cumulative events of bradycardia (rate/duration time). Bradycardia is defined as low heart rate (HR < 50/min). | 0-3 days, following surgery |
| Participants Number of Days Spent Post-operative Hospitalization | Measurement of participants number of days spent hospitalized (0-3 days) following surgery. | 0-3 days following surgery |
| Patient Recovery Progress Events at 30-days Post-operative. | Measured number of participant post-operative recovery events, 30-days following the surgical procedure. | 30-days from surgery |
| Participant Post-operative Mortality at 1-year Following Surgery | Measured number of patient post-operative mortality at 1-year. Measured by 'living', 'deceased', 'date of death'. | 1-Year from surgery |
| Post-operatively, 0-3 days, and day-30 |
| St Louis |
| Missouri |
| 63110 |
| United States |
| BG001 | 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). Placebo: 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). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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). Placebo: 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). Post-operative analysis to determine Myocardial Injury (hs-cTnT) in randomized placebo group. |
|
|
| Secondary | Effectiveness in Reduction of Major Adverse Cardiac Events (MACE) | MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization | MACE analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, having myocardial ischemia, cardiac death, or coronary revascularization. | Posted | Number | participants | 0-3 days, following surgery |
|
|
|
| Secondary | 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 | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, with post-operative cardiac monitoring (ECG), showing 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 | Posted | Count of Participants | Participants | 0-3 days, following surgery |
|
|
|
| Secondary | Number of Stroke Related Events Following Surgery | Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, with post-operative sudden onset of neurological effects from cerebral dysfunction. | Posted | Count of Participants | Participants | 0-3 days, following surgery |
|
|
|
| Secondary | Number of Participants Having Vasopressor Therapy to Regulate Symptomatic Hypotension | Monitor participants with vasopressor requirements for blood pressure regulation due to symptomatic hypotension (rate/duration time). 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. | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, having significant post-operative hypotension (systolic BP < 90 mmHg), requiring therapeutic intervention (vasopressor). | Posted | Count of Participants | Participants | 0-3 days, following surgery |
|
|
|
| Secondary | Number of Participant Incidence of Clinically Relevant Bradycardia | Monitored participants with cumulative events of bradycardia (rate/duration time). Bradycardia is defined as low heart rate (HR < 50/min). | Posted | Count of Participants | Participants | 0-3 days, following surgery |
|
|
|
| Secondary | Participants Number of Days Spent Post-operative Hospitalization | Measurement of participants number of days spent hospitalized (0-3 days) following surgery. | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, with post-operative length of hospital stay in days. | Posted | Median | Full Range | days | 0-3 days following surgery |
|
|
|
| Secondary | Patient Recovery Progress Events at 30-days Post-operative. | Measured number of participant post-operative recovery events, 30-days following the surgical procedure. | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, with post-operative 1-month follow up showing readmission since surgical discharge. | Posted | Count of Participants | Participants | 30-days from surgery |
|
|
|
| Secondary | Participant Post-operative Mortality at 1-year Following Surgery | Measured number of patient post-operative mortality at 1-year. Measured by 'living', 'deceased', 'date of death'. | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, deceased within 1-year of post-operative discharge. | Posted | Count of Participants | Participants | 1-Year from surgery |
|
|
|
| Other Pre-specified | Measured Number of Patient Adverse Events | Number of measured participant 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. | Analysis is comprised of eligible participants meeting criteria for randomization to receive intervention, having post-operative adverse events. | Posted | Count of Participants | Participants | Post-operatively, 0-3 days, and day-30 |
|
|
|
| 0 |
| 34 |
| 0 |
| 34 |
| 8 |
| 34 |
| EG001 | 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). Placebo: 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). Post-operative analysis to determine Myocardial Injury (hs-cTnT) in randomized placebo group. | 0 | 38 | 0 | 38 | 3 | 38 |
|
|
| Hypotension event | Cardiac disorders | Non-systematic Assessment | A recorded period when systolic blood pressure reading was lower than 90 mm Hg. |
|
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| D001157 |
| Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D018674 | Adrenergic Antagonists |
| D018663 | Adrenergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |
| Death |
|
| Cardiac Arrest |
|