The GUARDIAN Trial - Induction Agent Sub-Study

The University of Texas System (UT)

Status and phase: Invitation-only; Phase 4

Conditions: Major Surgery

Treatments: Drug: Propofol Induction; Procedure: Routine Blood Pressure Management; Drug: Etomidate Induction; Procedure: Tight Blood Pressure Management

Study type: Interventional

Funder types: Other

Identifiers

NCT04934683

HSC-MS-24-1026 (induction)

Details and patient eligibility

About

This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to etomidate vs propofol for anesthetic induction.

Full description

Participants 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). Participants in this sub-study will be additionally randomized to etomidate or propofol for induction of anesthesia.

Enrollment: 6,254 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. At least 45 years old;

2. Scheduled for major noncardiac surgery expected to last at least 2 hours;

3. Having general anesthesia, neuraxial anesthesia, or the combination;

4. Expected to require at least overnight hospitalization (planned ICU admission is acceptable);

5. Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);

6. Expected to have direct intraoperative blood pressure monitoring with an arterial catheter;

7. Cared for by clinicians willing to follow the GUARDIAN protocol;

8. Subject to at least one of the following risk factors:

   1. Age >65 years;
   2. History of peripheral arterial disease;
   3. History of coronary artery disease;
   4. History of stroke or transient ischemic attack;
   5. Serum creatinine >175 μmol/L (>2.0 mg/dl) within 6 months;
   6. Diabetes requiring medication;
   7. Current smoking or 15 pack-year history of smoking tobacco;
   8. Scheduled for major vascular surgery;
   9. Body mass index ≥35 kg/m2;
   10. Preoperative high-sensitivity troponin T >14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays - all within 6 months;
   11. B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NTProBNP) >200 ng/L within six months.

Exclusion criteria

1. Are scheduled for carotid artery surgery;
2. Are scheduled for intracranial surgery;
3. Are scheduled for partial or complete nephrectomy;
4. Are scheduled for pheochromocytoma surgery;
5. Are scheduled for liver or kidney transplantation;
6. Require preoperative intravenous vasoactive medications;
7. Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
8. Require beach-chair positioning;
9. Have a documented history of dementia;
10. Have language, vision, or hearing impairments that may compromise cognitive assessments;
11. Have contraindications to norepinephrine or phenylephrine per clinician judgement;
12. Have previously participated in the GUARDIAN trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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6,254 participants in 4 patient groups

Routine Blood Pressure Management and Etomidate Induction

Active Comparator group

Description:

Etomidate will be used as the anesthetic induction agent.

Treatment:

Drug: Etomidate Induction

Procedure: Routine Blood Pressure Management

Routine Blood Pressure Management and Propofol Induction

Active Comparator group

Description:

Propofol will be used as the anesthetic induction agent.

Treatment:

Drug: Propofol Induction

Procedure: Routine Blood Pressure Management

Tight Blood Pressure Management and Etomidate Induction

Active Comparator group

Description:

Etomidate will be used as the anesthetic induction agent.

Treatment:

Procedure: Tight Blood Pressure Management

Drug: Etomidate Induction

Tight Blood Pressure Management and Propofol Induction

Active Comparator group

Description:

Propofol will be used as the anesthetic induction agent.

Treatment:

Procedure: Tight Blood Pressure Management

Drug: Propofol Induction