GUARDIAN (NCT04884802) Sub-study, Etomidate vs Propofol

GUARDIAN (NCT04884802) Sub-study Comparing Etomidate and Propofol

Some patients participating in the underlying GUARDIAN trial (NCT04884802) will be additionally randomized to etomidate vs propofol for anesthetic induction.

Study Overview

• Status: Recruiting
• Conditions: Major Surgery
• Intervention / Treatment: Procedure: Routine blood pressure control; Drug: Etomidate; Drug: Propofol; Procedure: Tight blood pressure control

Detailed Description

Patients participating in the underlying GUARDIAN trial (NCT04884802) will be randomized to: 1) routine intraoperative blood pressure management (routine pressure management); or 2) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management). Patients participating in this sub-study will be additionally randomized to etomidate or propofol for induction of anesthesia.

• Study Type: Interventional
• Enrollment (Estimated): 6254
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fabio Rodriquez Patarroyo, MD; Phone Number: 216) 444-9674‬; Email: Rodrigf3@ccf.org
• Study Contact Backup: Name: Daniel I Sessler, MD; Phone Number: 216-870-2620; Email: sessled@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Fabio Rodriquez Patarroyo, MD; Phone Number: 216-444-9674; Email: Rodrigf3@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At least 45 years old;
• Scheduled for major noncardiac surgery expected to last at least 2 hours;
• Having general anesthesia, neuraxial anesthesia, or the combination;
• Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
• Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
• Chronically taking at least one anti-hypertensive medication;
• Expected to have direct intraoperative blood pressure monitoring with an arterial catheter;
• Cared for by clinicians willing to follow the GUARDIAN protocol;
• Subject to at least one of the following risk factors:
• Age >65 years;
• History of peripheral arterial surgery;
• History of coronary artery disease;
• History of stroke or transient ischemic attack;
• Serum creatinine >175 µmol/L (>2.0 mg/dl);
• Diabetes requiring medication;
• Current smoking or 15 pack-year history of smoking tobacco;
• Scheduled for major vascular surgery;
• Body mass index ≥35 kg/m2;
• Preoperative high-sensitivity troponin T >14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay),77 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays;
• B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) >200 ng/L.78,79

Exclusion Criteria:

• Are scheduled for carotid artery surgery;
• Are scheduled for intracranial surgery;
• Are scheduled for partial or complete nephrectomy;
• Are scheduled for pheochromocytoma surgery;
• Are scheduled for liver transplantation;
• Require preoperative intravenous vasoactive medications;
• Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
• Require beach-chair positioning;
• Have end-stage renal disease requiring dialysis or estimated glomerular filtration rate (eGFR) <30 ml/min;
• Have a documented history of dementia;
• Have language, vision, or hearing impairments that may compromise cognitive assessments;
• Have contraindications to norepinephrine or phenylephrine per clinician judgement;
• Have previously participated in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Routine Pressure Management with etomidate induction; Etomidate will be used as an induction agent.	Procedure: Routine blood pressure control; Routine blood pressure control.; Drug: Etomidate; Anesthetic induction with etomidate.
Active Comparator: Routine Pressure Management with propofol induction; Propofol will be used as an induction agent.	Procedure: Routine blood pressure control; Routine blood pressure control.; Drug: Propofol; Anesthetic induction with propofol.
Active Comparator: Tight Pressure Management with etomidate induction; Etomidate will be used as an induction agent.	Drug: Etomidate; Anesthetic induction with etomidate.; Procedure: Tight blood pressure control; Tight blood pressure control.
Active Comparator: Tight Pressure Management with propofol induction; Propofol will be used as an induction agent.	Drug: Propofol; Anesthetic induction with propofol.; Procedure: Tight blood pressure control; Tight blood pressure control.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of serious perfusion-related complications	Composite of serious perfusion-related complications. Specifically, we will consider a collapsed (one or more) composite of myocardial injury after non-cardiac surgery (MINS), non-fatal cardiac arrest, stroke, Stage 2-3 acute kidney injury, sepsis, and all-cause mortality within 30 days of surgery.	30 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Delirium	Delirium, defined by abnormal 3D CAM or CAM ICU (in ventilated patients) assessed twice daily during the initial four postoperative days.	Initial four postoperative days
Major Adverse cardiac events	Myocardial infarction, non-fatal cardiac arrest, stroke, and all-cause mortality.	1 year
Cognition	T-MOCA	1 Year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU admission	Admission.	30 days.
Hospital Readmission	Readmission.	30 days.
Atrial Fibrillation	Atrial Fibrillation.	30 days.

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Daniel I Sessler, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: June 15, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 22, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol; Etomidate
• Other Study ID Numbers: GUARDIAN INDUCTION AGENT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared collaboratively.
• IPD Sharing Time Frame: 2 years after publication.
• IPD Sharing Access Criteria: Contact PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No