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

• Status: Enrolling by invitation
• Trial end date: 2025-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Cleveland Clinic
• Treatments: Norepinephrine; Oxymetazoline; Phenylephrine

Criteria

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14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay),77 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays;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.