Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The GUARDIAN Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04884802
Recruitment Status : Recruiting
First Posted : May 13, 2021
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
The Cleveland Clinic

Brief Summary:
The treatments will be: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg, delayed resumption of chronic antihypertensive medications, and a target ward systolic pressure ≥110 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management and prompt resumption of chronic antihypertensive medications (routine pressure management).

Condition or disease Intervention/treatment Phase
Blood Pressure Procedure: Tight pressure management Procedure: Routine pressure management Drug: Induction agent Drug: Vasopressor Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6254 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel group randomized trial.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications.
Actual Study Start Date : July 25, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : April 25, 2025

Arm Intervention/treatment
Experimental: Tight 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.

Resumption of chronic anti-hypertensive medications will be delayed until the third postoperative day unless deemed necessary to treat hypertension or for some other clear indication.

The target for postoperative systolic arterial pressures ≥110 mmHg during the initial three postoperative days.

Procedure: Tight pressure management
Norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg, delayed resumption of chronic antihypertensive medications, and a target ward MAP ≥80 mmHg (tight pressure management)

Drug: Induction agent
etomidate and propofol - randomly assigned
Other Name: etomidate and propofol

Drug: Vasopressor
pressure maintenance with phenylephrine and norepinephrine - randomly assigned
Other Name: phenylephrine and norepinephrine

Routine 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. As usual, chronic anti-hypertensive medications will be restarted shortly after surgery unless contraindicated by hypotension.
Procedure: Routine 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. As usual, chronic anti-hypertensive medications will be restarted shortly after surgery unless contraindicated by hypotension.

Drug: Induction agent
etomidate and propofol - randomly assigned
Other Name: etomidate and propofol

Drug: Vasopressor
pressure maintenance with phenylephrine and norepinephrine - randomly assigned
Other Name: phenylephrine and norepinephrine




Primary Outcome Measures :
  1. Composite of major perfusion-related complications [ Time Frame: 30 days after major non-cardiac surgery ]
    a composite of major perfusion-related complications (myocardial injury, stroke, non-fatal cardiac arrest, Stage 2-3 acute kidney injury, sepsis, and death)


Secondary Outcome Measures :
  1. Postoperative delirium [ Time Frame: 4 Postoperative hospital days ]
    Three-dimensional Confusion Assessment Method (3D CAM)

  2. Major adverse cardiac events [ Time Frame: 1 year ]
    Myocardial infarction, non-fatal cardiac arrest, stroke, and all-cause mortality.

  3. Cognition [ Time Frame: 1 year ]
    T-MOCA


Other Outcome Measures:
  1. ICU admission [ Time Frame: 30 days. ]
    Admission.

  2. Hospital readmission [ Time Frame: 30 days. ]
    Readmission.

  3. Atrial fibrillation [ Time Frame: 30 days. ]
    Atrial fibrillation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 through severe 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; defined as ≥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 or N-terminal B-type natriuretic protein (NT-ProBNP) >200 ng/L

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04884802


Contacts
Layout table for location contacts
Contact: Roberta Johnson 216-444-9950 johnsor13@ccf.org

Locations
Layout table for location information
China
Peking Union Medical College Hospital Recruiting
Beijing, China
Contact: Yu-Guang Huang, MD         
Peking University First Hospital Not yet recruiting
Beijing, China
Contact: Dong-Xin Wang, MD         
China-Japan Union Hospital of Jilin University Recruiting
Chang Chun, China
Contact: Kai Li, MD         
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Layout table for investigator information
Study Chair: Daniel I Sessler, MD The Cleveland Clinic
Layout table for additonal information
Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT04884802    
Other Study ID Numbers: 21-175
First Posted: May 13, 2021    Key Record Dates
Last Update Posted: August 18, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared on a collaborative basis.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Within two years after publication of the main trial report, and for at least 5 years thereafter.
Access Criteria: Daniel Sessler at DS@OR.org.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Phenylephrine
Norepinephrine
Vasoconstrictor Agents
Propofol
Etomidate
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Cardiotonic Agents
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Sympathomimetics
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents