The GUARDIAN Trial

Last updated: August 23, 2024
Sponsor: The Cleveland Clinic
Overall Status: Active - Recruiting

Phase

N/A

Condition

N/A

Treatment

Routine pressure management

Tight pressure management

Clinical Study ID

NCT04884802
21-175
  • Ages > 45
  • All Genders

Study Summary

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:

  • ≥45 years old

  • Scheduled for major noncardiac surgery expected to last at least 2 hours;

  • Having general endotracheal, neuraxial anesthesia, or the combination;

  • Expected to require at least overnight hospitalization;

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

  • Chronically taking at least one anti-hypertensive medication;

  • Expected to have direct 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:

  • 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);

  • 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14 ng/L or troponin I equivalent; definedas ≥15 ng/L (Abbott assay),73 19 ng/L (Siemens assay, [Borges, unpublished]), or 50%of the 99% percentile for other assays; B-type natriuretic protein (BNP) >80 ng/L orN-terminal B-type natriuretic protein (NT-ProBNP) >200 ng/L

Exclusion

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 assurgeon request for relative hypotension;

  • Require beach-chair positioning;

  • Have a documented history of dementia;

  • Have language, vision, or hearing impairments that may compromise cognitiveassessments;

  • Have contraindications to norepinephrine or phenylephrine per clinician judgement;

  • Have previously participated in the GUARDIAN trial.

Study Design

Total Participants: 6254
Treatment Group(s): 2
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. A norepinephrine or phenylephrine infusion (in the preferred local concentration) will be prepared, connected to an intravenous catheter, and activated at a low rate. Norepinephrine can be safely given through a central catheter or peripherally. 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. Clinicians will be encouraged to use etomidate when rapid-sequence inductions are required. 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. Blood pressure will not be deliberately reduced, but per routine clinicians will presumably not intervene until MAP is <60 mmHg - although they are free to.

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. Clinicians should always act in their patients' best interests, irrespective of the GUARDIAN protocol.

Connect with a study center

  • Beijing Shijitan Hospital, Capital Medical University

    Beijing,
    China

    Active - Recruiting

  • Peking Union Medical College Hospital

    Beijing,
    China

    Active - Recruiting

  • Peking University First Hospital

    Beijing,
    China

    Site Not Available

  • China-Japan Union Hospital of Jilin University

    Chang Chun,
    China

    Active - Recruiting

  • West China University Hospital

    Chengdu,
    China

    Active - Recruiting

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

    Hong Kong,
    China

    Active - Recruiting

  • Shanghai Chest Hospital

    Shanghai,
    China

    Site Not Available

  • Shanghai Ninth People's Hospital

    Shanghai,
    China

    Active - Recruiting

  • University of Thessaly

    Larisa,
    Greece

    Active - Recruiting

  • IRCCS Regina Elena National Cancer Institute

    Rome,
    Italy

    Active - Recruiting

  • National Defense Medical College

    Tokyo,
    Japan

    Active - Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Active - Recruiting

  • Wake Forest University

    Wake Forest, North Carolina 27106
    United States

    Active - Recruiting

  • 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

    Active - Recruiting

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