The GUARDIAN Trial

August 23, 2025 updated by: Daniel Sessler, The University of Texas Health Science Center, Houston

Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications: The GUARDIAN Trial

An international randomized trial to test the primary hypothesis that perioperative tight blood pressure management reduces 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.

The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Qualifying patients will be randomized 1:1, with random-sized blocks, stratified by site. The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management).

Tight pressure management: In patients assigned to tight pressure management, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. General anesthesia will be induced with propofol or etomidate which will be given in repeated small boluses or target-controlled infusion in an effort to keep mean arterial pressure ≥85 mmHg. Simultaneously, the vasopressor infusion will be adjusted with the same goal. Anesthetic dose, fluid administration, and vasopressor administration will be adjusted with the goal of maintaining the individual designated baseline mean arterial pressure. Invasive or non-invasive advanced hemodynamic monitoring is not required, but should be used when practical. Clinicians should use available information to optimize vascular volume, afterload, and inotropy.

Routine pressure management: In patients assigned to routine pressure management, ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. General anesthesia will be induced and maintained per routine.

In both groups, other aspects of anesthetic management will be at the discretion of the responsible anesthesiologist, including the types and volumes of various fluids. Volatile or intravenous anesthesia is permitted. There will be no limitation on ancillary vasoactive, chronotropic, and inotropic drugs. Clinicians will be free to use advanced hemodynamic monitoring (e.g., pulse-wave analysis, esophageal Doppler, etc.). Blood products will be given per routine. Similarly, postoperative analgesic management will be per routine and clinician preference. Neuraxial and peripheral nerve blocks are permitted, but epidural catheters should not be activated until surgery is nearly finished.

In all cases, good judgement will predominate.

Study Type

Interventional

Enrollment (Estimated)

6254

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China
      • Beijing, China
        • Recruiting
        • Peking University First Hospital
        • Contact:
          • Dong-Xin Wang, MD
      • Beijing, China
        • Recruiting
        • Beijing Shijitan Hospital, Capital Medical University
        • Contact:
      • Chengdu, China
        • Recruiting
        • West China University Hospital
        • Contact:
          • Xiao Liang, MD
      • Hong Kong, China
        • Recruiting
        • Prince of Wales Hospital, Chinese University of Hong Kong, Shatin
        • Contact:
      • Shanghai, China
        • Recruiting
        • Shanghai Chest Hospital
        • Contact:
        • Principal Investigator:
          • Jingxiang Wu, MD
      • Shanghai, China
        • Recruiting
        • Renji Hospital, Shanghai Jiaotong University School of Medicine
        • Contact:
      • Shanghai, China
      • Xuzhou, China
        • Recruiting
        • The Affiliated Lianyungang Hospital of Xuzhou Medical University
        • Contact:
  • Greece
      • Larissa, Greece
        • Completed
        • University of Thessaly
  • Italy
      • Rome, Italy
        • Recruiting
        • IRCCS Regina Elena National Cancer Institute
        • Contact:
  • Japan
  • Turkey (Türkiye)
      • Bakırköy, Turkey (Türkiye)
      • Konya, Turkey (Türkiye)
  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Completed
        • University of Nebraska Medical Center
    • North Carolina
      • Wake Forest, North Carolina, United States, 27106
        • Completed
        • Wake Forest University
    • Ohio
      • Cleveland, Ohio, United States, 44109
      • Cleveland, Ohio, United States, 44111
        • Completed
        • Cleveland Clinic Fairview Hospital
      • Cleveland, Ohio, United States, 44195
        • Completed
        • Cleveland Clinic Main Campus
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Health Science Center at Houston
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. At least 45 years old;
  2. Scheduled for major noncardiac surgery expected to last at least 2 hours;
  3. Having general anesthesia, neuraxial anesthesia, or the combination;
  4. Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
  5. Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
  6. Expected to have direct intraoperative blood pressure monitoring with an arterial catheter;
  7. Cared for by clinicians willing to follow the GUARDIAN protocol;

  8. Subject to at least one of the following risk factors:

    1. Age >65 years;
    2. History of peripheral arterial disease;
    3. History of coronary artery disease;
    4. History of stroke or transient ischemic attack;
    5. Serum creatinine >175 μmol/L (>2.0 mg/dl) within 6 months;
    6. Diabetes requiring medication;
    7. Current smoking or 15 pack-year history of smoking tobacco;
    8. Scheduled for major vascular surgery;
    9. Body mass index ≥35 kg/m2;
    10. 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;
    11. B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NTProBNP) >200 ng/L within six months.

Exclusion Criteria:

  1. Are scheduled for carotid artery surgery;
  2. Are scheduled for intracranial surgery;
  3. Are scheduled for partial or complete nephrectomy;
  4. Are scheduled for pheochromocytoma surgery;
  5. Are scheduled for liver or kidney transplantation;
  6. Require preoperative intravenous vasoactive medications;
  7. Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
  8. Require beach-chair positioning;
  9. Have a documented history of dementia;
  10. Have language, vision, or hearing impairments that may compromise cognitive assessments;
  11. Have contraindications to norepinephrine or phenylephrine per clinician judgement;
  12. Have previously participated in the GUARDIAN trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tight blood pressure management
In patients assigned to tight blood pressure control, angiotensin converting enzyme inhibitors and angiotensin receptor blockers will not be given the morning of surgery. Other chronic antihypertensives will only be given as necessary to treat hypertension. Norepinephrine or phenylephrine infusion will be infused at a rate sufficient to maintain intraoperative MAP ≥ 85 mmHg.
Procedure: Tight blood pressure management
Norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg.
Other: Routine blood pressure management
ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine.
Procedure: Routine blood pressure management
ACEIs, ARBs, and/or calcium channel blockers can be given the morning of surgery if deemed appropriate by the attending anesthesiologist. Intraoperative blood pressure will be managed per clinical routine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
During the initial 30 days after major non-cardiac surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants with Postoperative Delirium
Time Frame: Initial 4 postoperative days.
The Postoperative 3-Minute Diagnostic Interview for the Confusion Assessment Method (3D CAM) will be used twice daily to assess for the presence of delirium.
Initial 4 postoperative days.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
ICU admission
Time Frame: 30 days.
Admission.
30 days.
Hospital readmission
Time Frame: 30 days.
Readmission.
30 days.
Atrial fibrillation
Time Frame: 30 days.
Atrial fibrillation
30 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Investigators

  • Principal Investigator: Daniel I Sessler, MD, The University of Texas Health Science Center, Houston

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 25, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

April 25, 2027

Study Registration Dates

First Submitted

April 5, 2021

First Submitted That Met QC Criteria

May 7, 2021

First Posted (Actual)

May 13, 2021

Study Record Updates

Last Update Posted (Estimated)

August 29, 2025

Last Update Submitted That Met QC Criteria

August 23, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-24-1026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

Within two years after publication of the main trial report, and for at least 5 years thereafter.

IPD Sharing Access Criteria

Daniel Sessler at DS@OR.org.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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