GUARDIAN (NCT04884802) Sub-study, Etomidate vs Propofol

Phase 3

Recruiting

• Conditions: Major Surgery
• Interventions: Procedure: Routine blood pressure control; Procedure: Tight blood pressure control; Drug: Etomidate; Drug: Propofol

• Registration Number: NCT04934683
• Lead Sponsor: The Cleveland Clinic

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-06-15
• Study First Submitted QC: 2021-06-15
• Study First Posted: 2021-06-22
• Study Start: 2021-07-27
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04
• Primary Completion: 2025-12
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 6254

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Routine Pressure Management with etomidate induction	Routine blood pressure control	Etomidate will be used as an induction agent.
Routine Pressure Management with propofol induction	Routine blood pressure control	Propofol will be used as an induction agent.
Tight Pressure Management with etomidate induction	Tight blood pressure control	Etomidate will be used as an induction agent.
Tight Pressure Management with propofol induction	Tight blood pressure control	Propofol will be used as an induction agent.
Routine Pressure Management with etomidate induction	Etomidate	Etomidate will be used as an induction agent.
Routine Pressure Management with propofol induction	Propofol	Propofol will be used as an induction agent.
Tight Pressure Management with etomidate induction	Etomidate	Etomidate will be used as an induction agent.
Tight Pressure Management with propofol induction	Propofol	Propofol will be used as an induction agent.

Primary Outcome Measures

Name	Time	Method
Composite of serious perfusion-related complications	30 days after surgery	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States