Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial (Vasopressor Sub-study Comparing Phenylephrine and Norepinephrine)
Trial Snapshot
- Phase
- Phase 4
- Status
- Enrolling By Invitation
- Enrollment
- 6,254
- Locations
- 11
- Primary Endpoint
- Number of Participants with a Composite of Major Perfusion-Related Complications
Study Overview
Brief Summary
This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.
Detailed Description
Participants 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). Participants in this sub-study will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Prevention
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 45 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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);
- •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 disease;
- •History of coronary artery disease;
- •History of stroke or transient ischemic attack;
- •Serum creatinine >175 μmol/L (>2.0 mg/dl) within 6 months;
- •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), 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays - all within 6 months;
- •B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NTProBNP) >200 ng/L within six months.
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.
Arms & Interventions
Tight Blood Pressure Management with Phenylephrine
TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Intervention: Tight Blood Pressure Management (Procedure)
Tight Blood Pressure Management with Phenylephrine
TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Intervention: Phenylephrine (Drug)
Routine Blood Pressure Management with Phenylephrine
Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Routine Blood Pressure Management (Procedure)
Routine Blood Pressure Management with Phenylephrine
Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Phenylephrine (Drug)
Routine Blood Pressure Management with Norepinephrine
Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Routine Blood Pressure Management (Procedure)
Routine Blood Pressure Management with Norepinephrine
Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Norepinephrine (Drug)
Tight Blood Pressure Management with Norepinephrine
Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Tight Blood Pressure Management (Procedure)
Tight Blood Pressure Management with Norepinephrine
Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Intervention: Norepinephrine (Drug)
Outcomes
Primary Outcomes
Number of Participants with a Composite of Major Perfusion-Related Complications
Time Frame: During the initial 30 days after major non-cardiac surgery
The primary outcome is a composite of major perfusion-related complications (myocardial injury, stroke, non-fatal cardiac arrest, Stage 2-3 acute kidney injury, deep or organ-space infection, sepsis, and death) in the 30 days after major non-cardiac surgery.
Secondary Outcomes
No secondary outcomes reported
Investigators
Daniel Sessler
Professor
The University of Texas Health Science Center, Houston