The GUARDIAN Trial

NCT ID: NCT04884802

Last Updated: 2025-08-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

6254 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-07-25

Study Completion Date

2027-04-25

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Blood Pressure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Tight blood pressure management

Intervention Type PROCEDURE

Norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg.

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.

Group Type OTHER

Routine blood pressure management

Intervention Type PROCEDURE

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.

Interventions

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Tight blood pressure management

Norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg.

Intervention Type 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.

Intervention Type PROCEDURE

Eligibility Criteria

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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.
Minimum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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Daniel Sessler

Professor and Vice President for Clinical and Outcomes Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daniel I Sessler, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

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University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status COMPLETED

Wake Forest University

Wake Forest, North Carolina, United States

Site Status COMPLETED

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, United States

Site Status COMPLETED

Cleveland Clinic Main Campus

Cleveland, Ohio, United States

Site Status COMPLETED

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status RECRUITING

Beijing Shijitan Hospital, Capital Medical University

Beijing, , China

Site Status RECRUITING

Peking Union Medical College Hospital

Beijing, , China

Site Status RECRUITING

Peking University First Hospital

Beijing, , China

Site Status RECRUITING

West China University Hospital

Chengdu, , China

Site Status RECRUITING

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

Hong Kong, , China

Site Status RECRUITING

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Shanghai Chest Hospital

Shanghai, , China

Site Status RECRUITING

Shanghai Ninth People's Hospital

Shanghai, , China

Site Status RECRUITING

The Affiliated Lianyungang Hospital of Xuzhou Medical University

Xuzhou, , China

Site Status RECRUITING

University of Thessaly

Larissa, , Greece

Site Status COMPLETED

IRCCS Regina Elena National Cancer Institute

Rome, , Italy

Site Status RECRUITING

National Defense Medical College

Tokyo, , Japan

Site Status RECRUITING

Bakirkoy Dr. Sadi Konuk Research and Training Hospital

Bakırköy, , Turkey (Türkiye)

Site Status RECRUITING

Konya City Hospital

Konya, , Turkey (Türkiye)

Site Status RECRUITING

Countries

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United States China Greece Italy Japan Turkey (Türkiye)

Central Contacts

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Valerie L. Anderson, BS

Role: CONTACT

(713) 500-4383

Daniel Sessler, MD

Role: CONTACT

(713) 500-3062

Facility Contacts

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Luis Tollinche, MD

Role: primary

Valerie Anderson, BS

Role: primary

713-500-4383

Yuefu Wang, MD

Role: primary

Hazel Pei, MD

Role: primary

Dong-Xin Wang, MD

Role: primary

Xiao Liang, MD

Role: primary

Matthew Chan, MD

Role: primary

Peiying Li Li, MD,Phd

Role: primary

Jingxiang Wu, MD

Role: primary

+86-18930857186

Hong Jiang, MD

Role: primary

Xiaobao Zhang, MD

Role: primary

Marco Covotta, MD

Role: primary

Tetsuya Shimada, MD

Role: primary

Gokhan Sertcakacilar, MD

Role: primary

Yasin Tire, MD

Role: primary

Other Identifiers

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HSC-MS-24-1026

Identifier Type: -

Identifier Source: org_study_id

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