The GUARDIAN Trial

Last updated: August 23, 2025
Sponsor: The University of Texas Health Science Center, Houston
Overall Status: Active - Recruiting

Phase

N/A

Condition

N/A

Treatment

Routine pressure management

Tight pressure management

Tight blood pressure management

Clinical Study ID

NCT04884802
HSC-MS-24-1026
  • Ages > 45
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

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 isacceptable);

  5. Are designated ASA physical status 2-4 (ranging from mild systemic disease throughsevere systemic disease that is a constant threat to life);

  6. Expected to have direct intraoperative blood pressure monitoring with an arterialcatheter;

  7. Cared for by clinicians willing to follow the GUARDIAN protocol;

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

  9. Age >65 years;

  10. History of peripheral arterial disease;

  11. History of coronary artery disease;

  12. History of stroke or transient ischemic attack;

  13. Serum creatinine >175 μmol/L (>2.0 mg/dl) within 6 months;

  14. Diabetes requiring medication;

  15. Current smoking or 15 pack-year history of smoking tobacco;

  16. Scheduled for major vascular surgery;

  17. Body mass index ≥35 kg/m2;

  18. 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14 ng/L or troponin I equivalent,defined as ≥15 ng/L (Abbott assay), 19 ng/L (Siemens assay, [Borges,unpublished]), or 25% of the 99% percentile for other assays - all within 6months;

  19. B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriureticprotein (NTProBNP) >200 ng/L within six months.

Exclusion

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 assurgeon 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 cognitiveassessments;

  11. Have contraindications to norepinephrine or phenylephrine per clinician judgement;

  12. Have previously participated in the GUARDIAN trial.

Study Design

Total Participants: 6254
Treatment Group(s): 4
Primary Treatment: Routine pressure management
Phase:
Study Start date:
July 25, 2021
Estimated Completion Date:
April 25, 2027

Study 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.

Connect with a study center

  • Beijing Shijitan Hospital, Capital Medical University

    Beijing,
    China

    Site Not Available

  • Peking Union Medical College Hospital

    Beijing,
    China

    Active - Recruiting

  • Peking University First Hospital

    Beijing,
    China

    Site Not Available

  • Beijing Shijitan Hospital, Capital Medical University

    Beijing 1816670,
    China

    Active - Recruiting

  • Peking Union Medical College Hospital

    Beijing 1816670,
    China

    Active - Recruiting

  • Peking University First Hospital

    Beijing 1816670,
    China

    Active - Recruiting

  • China-Japan Union Hospital of Jilin University

    Chang Chun,
    China

    Site Not Available

  • West China University Hospital

    Chengdu,
    China

    Site Not Available

  • West China University Hospital

    Chengdu 1815286,
    China

    Active - Recruiting

  • Prince of Wales Hospital, Chinese University of Hong Kong, Shatin

    Hong Kong,
    China

    Site Not Available

  • Prince of Wales Hospital, Chinese University of Hong Kong, Shatin

    Hong Kong 1819729,
    China

    Active - Recruiting

  • Shanghai Chest Hospital

    Shanghai,
    China

    Site Not Available

  • Shanghai Ninth People's Hospital

    Shanghai,
    China

    Site Not Available

  • Renji Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai 1796236,
    China

    Active - Recruiting

  • Shanghai Chest Hospital

    Shanghai 1796236,
    China

    Active - Recruiting

  • Shanghai Ninth People's Hospital

    Shanghai 1796236,
    China

    Active - Recruiting

  • The Affiliated Lianyungang Hospital of Xuzhou Medical University

    Xuzhou 10630003,
    China

    Active - Recruiting

  • University of Thessaly

    Larisa,
    Greece

    Site Not Available

  • University of Thessaly

    Larissa 258576,
    Greece

    Completed

  • IRCCS Regina Elena National Cancer Institute

    Rome,
    Italy

    Site Not Available

  • IRCCS Regina Elena National Cancer Institute

    Rome 3169070,
    Italy

    Active - Recruiting

  • National Defense Medical College

    Tokyo,
    Japan

    Site Not Available

  • National Defense Medical College

    Tokyo 1850147,
    Japan

    Active - Recruiting

  • Bakirkoy Dr. Sadi Konuk Research and Training Hospital

    Bakırköy 751213,
    Turkey (Türkiye)

    Active - Recruiting

  • Konya City Hospital

    Konya 306571,
    Turkey (Türkiye)

    Active - Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Site Not Available

  • University of Nebraska Medical Center

    Omaha 5074472, Nebraska 5073708 68198
    United States

    Completed

  • Wake Forest University

    Wake Forest, North Carolina 27106
    United States

    Site Not Available

  • Wake Forest University

    Wake Forest 4497290, North Carolina 4482348 27106
    United States

    Completed

  • Cleveland Clinic

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • Cleveland Clinic Fairview Hospital

    Cleveland, Ohio 44111
    United States

    Active - Recruiting

  • MetroHealth Medical Center

    Cleveland, Ohio 44109
    United States

    Site Not Available

  • Cleveland Clinic Fairview Hospital

    Cleveland 5150529, Ohio 5165418 44111
    United States

    Completed

  • Cleveland Clinic Main Campus

    Cleveland 5150529, Ohio 5165418 44195
    United States

    Completed

  • MetroHealth Medical Center

    Cleveland 5150529, Ohio 5165418 44109
    United States

    Active - Recruiting

  • The University of Texas Health Science Center at Houston

    Houston 4699066, Texas 4736286 77030
    United States

    Active - Recruiting

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