The GUARDIAN Trial - Vasopressor Sub-Study
Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial (Vasopressor Sub-study Comparing Phenylephrine and Norepinephrine)
1 other identifier
interventional
6,254
4 countries
11
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jul 2021
Longer than P75 for phase_4
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 14, 2021
CompletedFirst Posted
Study publicly available on registry
June 22, 2021
CompletedStudy Start
First participant enrolled
July 25, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 25, 2027
August 29, 2025
July 1, 2025
5.4 years
June 14, 2021
August 23, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Participants with a Composite of Major Perfusion-Related Complications
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.
During the initial 30 days after major non-cardiac surgery
Study Arms (4)
Routine Blood Pressure Management with Phenylephrine
ACTIVE COMPARATORRoutine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Routine Blood Pressure Management with Norepinephrine
ACTIVE COMPARATORRoutine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Tight Blood Pressure Management with Phenylephrine
ACTIVE COMPARATORTIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Tight Blood Pressure Management with Norepinephrine
ACTIVE COMPARATORTight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Interventions
Routine blood pressure control.
Tight blood pressure control.
Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Eligibility Criteria
You may qualify if:
- 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;
- +4 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
MetroHealth Medical Center
Cleveland, Ohio, 44109, United States
Cleveland Clinic Fairview Hospital
Cleveland, Ohio, 44111, United States
Cleveland Clinic Main Campus
Cleveland, Ohio, 44195, United States
Beijing Shijitan Hospital, Capital Medical University
Beijing, China
Peking Union Medical College Hospital
Beijing, China
Shanghai Ninth People's Hospital
Shanghai, 200025, China
Shanghai Chest Hospital
Shanghai, China
West China Hospital
Sichuan, China
University of Thessaly
Larissa, Greece
National Defense College
Tokyo, Japan
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Daniel I Sessler, MD
The University of Texas Health Science Center, Houston
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
June 14, 2021
First Posted
June 22, 2021
Study Start
July 25, 2021
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
April 25, 2027
Last Updated
August 29, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will share
Each center will retain ownership of its own data. Publication of center-specific data will not be allowed until after the Main Trial Report is published, or two years have elapsed since enrollment of the last patient. The Executive Committee welcomes suggestions for sub-studies based on a partial or the full trial dataset. Sub-studies will be allocated based on importance and novelty of the proposals, and priority will be given to high-enrolling centers. However, all multi-center publications will be on a collaborative basis and include appropriate co-authors. The Executive Committee will do its best to be fair and equitable in assigning sub-studies. Data will be shared with external parties on a collaborative basis with approval of the Executive Committee and appropriate data-use agreements.