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

Blood Pressure Clinical Trial

Official title:

GUARDIAN (NCT04884802) Sub-study Comparing Phenylephrine and Norepinephrine

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04934748
• Other study ID #: GUARDIAN, Vasopressor
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: July 15, 2021
• Est. completion date: July 2025

Study information

• Verified date: August 2023
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 6254
• Est. completion date: July 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Pressure

Intervention

Drug:
• Phenylephrine
Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
• Norepinephrine
Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
• Phenylephrine
Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
• Norepinephrine
Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of major perfusion-related complications	Composite of major perfusion-related complications (Myocardial injury, stroke, non-fatal cardiac arrest, stage 2-3 acute kidney injury, sepsis, and death	30 days after major non-cardiac surgery
Secondary	Postoperative delirium	Three dimensional Confusion Assessment Method (3D CAM)	4 Postoperative hospital days