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Heart DiseasesPhase 3ORIONNCT03138603

Metoprolol to Reduce Perioperative Myocardial Injury

A Phase 3 study testing Metoprolol Tartrate in people with Heart Diseases, run by University of Chicago at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Heart Diseases
What is being tested?
Metoprolol Tartrate
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
72 participants
Where
2 sitesUnited States
Study dates
Dec 2016to 29 Aug 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • At high risk for CAD (must meet at least 2 criteria):
  • 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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Chicago Medicine

    Chicago, Illinois, 60637

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

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).

Read the 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.

Conditions
Heart Diseases
Being tested
Metoprolol Tartrate, Placebo
Keywords
surgery, heart disease, metoprolol, myocardial injury, coronary artery disease
Medical subject headings
Heart Diseases, Coronary Artery Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metoprolol TartrateDrug

    Also called Beta-blocker

    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).

  • PlaceboDrug

    Also called Sham, Placebo-comparator, Control

    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).

Study groups in NCT03138603
Study groupRoleWhat they receive
MetoprololExperimentalMetoprolol 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).
Receives: Drug: Metoprolol Tartrate
PlaceboPlacebo comparatorPlacebo 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).
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 0-3 days, following surgery

Secondary outcomes (8)

  1. Effectiveness in Reduction of Major Adverse Cardiac Events (MACE)

    MACE are defined as myocardial ischemia (MI), cardiac death or coronary revascularization

    Measured: 0-3 days, following surgery

  2. 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

    Measured: 0-3 days, following surgery

  3. Number of Stroke Related Events Following Surgery

    Stroke will be defined as focal or global cerebral, spinal, or retinal dysfunction of sudden onset

    Measured: 0-3 days, following surgery

  4. 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.

    Measured: 0-3 days, following surgery

  5. 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).

    Measured: 0-3 days, following surgery

  6. Participants Number of Days Spent Post-operative Hospitalization

    Measurement of participants number of days spent hospitalized (0-3 days) following surgery.

    Measured: 0-3 days following surgery

  7. Patient Recovery Progress Events at 30-days Post-operative.

    Measured number of participant post-operative recovery events, 30-days following the surgical procedure.

    Measured: 30-days from surgery

  8. 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'.

    Measured: 1-Year from surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2017
  2. Study startDec 2016
  3. Primary completion18 Apr 2023
  4. Study completion29 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Single-center, double blinded placebo controlled
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03138603
Sponsor's protocol ID
IRB19-1797
Other IDs
5R01HL126892
Acronym
ORION
Status last verified
Jan 2026
First submitted
26 Apr 2017
Last updated
28 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 41105735

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metoprolol Tartrate in people with Heart Diseases, run by University of Chicago at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effectiveness of Beta-blocker Therapy Reducing Post-operative Myocardial Injury (time frame: 0-3 days, following surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03138603, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2026.

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