GUARDIAN (NCT04884802) Sub-study, Phenylephrine v. Norepinephrine

Phase 4

• Conditions: Blood Pressure
• Interventions: Drug: Phenylephrine; Drug: Norepinephrine

• Registration Number: NCT04934748
• Lead Sponsor: The Cleveland Clinic

Brief Summary

Some patients participating in the underlying GUARDIAN trial (NCT04884802) will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Detailed Description

Patients participating in the underlying GUARDIAN trial (NCT04884802) will be randomized to: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management). Patients participating in this sub-study will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Study Timeline

• Study First Submitted: 2021-06-14
• Study First Submitted QC: 2021-06-15
• Study First Posted: 2021-06-22
• Study Start: 2021-07-15
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-28
• Last Update Posted: 2023-08-30
• Primary Completion: 2024-12
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• 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 or kidney 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 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 the GUARDIAN trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Tight Pressure Management with phenylephrine	Phenylephrine	Pressure maintenance with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Tight Pressure Management with norepinephrine	Norepinephrine	Pressure maintenance with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Routine Pressure Management with phenylephrine	Phenylephrine	Pressure maintenance with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Routine Pressure Management with norepinephrine	Norepinephrine	Pressure maintenance with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Primary Outcome Measures

Name	Time	Method
Composite of major perfusion-related complications	30 days after major non-cardiac surgery	Composite of major perfusion-related complications (Myocardial injury, stroke, non-fatal cardiac arrest, stage 2-3 acute kidney injury, sepsis, and death

Secondary Outcome Measures

Name	Time	Method
Postoperative delirium	4 Postoperative hospital days	Three dimensional Confusion Assessment Method (3D CAM)

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States