The GUARDIAN Trial

Blood Pressure Clinical Trial

Official title:

Tight Perioperative Blood Pressure Management to Reduce Serious Cardiovascular, Renal, and Cognitive Complications.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04884802
• Other study ID #: 21-175
• Status: Recruiting
• Phase: N/A
• Start date: July 25, 2021
• Est. completion date: April 25, 2025

Study information

• Verified date: August 2023
• Source: The Cleveland Clinic
• Contact: Fabio Rodriguez Patarroyo, MD
• Phone: ?(216) 444-9674?
• Email: Rodrigf3[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6254
• Est. completion date: April 25, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Blood Pressure

Intervention

Procedure:
• Tight pressure management
Norepinephrine or phenylephrine infusion to maintain intraoperative MAP =85 mmHg.
• 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.

Locations

Country	Name	City	State
China	Beijing Shijitan Hospital, Capital Medical University	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University First Hospital	Beijing
China	China-Japan Union Hospital of Jilin University	Chang Chun
China	West China University Hospital	Chengdu
China	Prince of Wales Hospital, Chinese University of Hong Kong, Shatin	Hong Kong
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Ninth People's Hospital	Shanghai
Greece	University of Thessaly	Larisa
Italy	IRCCS Regina Elena National Cancer Institute	Rome
Japan	National Defense Medical College	Tokyo
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic Fairview Hospital	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Wake Forest University	Wake Forest	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Countries where clinical trial is conducted

United States,  China,  Greece,  Italy,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ICU admission	Admission.	30 days.
Other	Hospital readmission	Readmission.	30 days.
Other	Atrial fibrillation	Atrial fibrillation	30 days.
Primary	Composite of major perfusion-related complications	a composite of major perfusion-related complications (myocardial injury, stroke, non-fatal cardiac arrest, Stage 2-3 acute kidney injury, sepsis, and death)	30 days after major non-cardiac surgery
Secondary	Postoperative delirium	Three-dimensional Confusion Assessment Method (3D CAM)	4 Postoperative hospital days
Secondary	Major adverse cardiac events	Myocardial infarction, non-fatal cardiac arrest, stroke, and all-cause mortality.	1 year
Secondary	Cognition	T-MOCA	1 year