Brief 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).

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6,254

participants targeted

Target at P75+ for not_applicable

Timeline
12mo left

Started Jul 2021

Longer than P75 for not_applicable

Geographic Reach
6 countries

20 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress83%
Jul 2021Apr 2027

First Submitted

Initial submission to the registry

April 5, 2021

Completed
1 month until next milestone

First Posted

Study publicly available on registry

May 13, 2021

Completed
2 months until next milestone

Study Start

First participant enrolled

July 25, 2021

Completed
5.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 25, 2027

Last Updated

August 29, 2025

Status Verified

July 1, 2025

Enrollment Period

5.4 years

First QC Date

April 5, 2021

Last Update Submit

August 23, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Number of Participants with a Composite of Major Perfusion-Related Complications

    The primary outcome is 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.

    During the initial 30 days after major non-cardiac surgery

Secondary Outcomes (1)

  • Number of Participants with Postoperative Delirium

    Initial 4 postoperative days.

Study Arms (2)

Tight blood pressure management

EXPERIMENTAL

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.

Procedure: Tight blood pressure management

Routine blood pressure management

OTHER

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.

Procedure: Routine blood pressure management

Interventions

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

Tight 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.

Routine blood pressure management

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • At least 45 years old;
  • Scheduled for major noncardiac surgery expected to last at least 2 hours;
  • Having general anesthesia, neuraxial anesthesia, or the combination;
  • Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
  • Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
  • Expected to have direct intraoperative 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:
  • Age \>65 years;
  • 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) within 6 months;
  • Diabetes requiring medication;
  • Current smoking or 15 pack-year history of smoking tobacco;
  • +4 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (20)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

COMPLETED

Wake Forest University

Wake Forest, North Carolina, 27106, United States

COMPLETED

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

RECRUITING

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, 44111, United States

COMPLETED

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195, United States

COMPLETED

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

Beijing Shijitan Hospital, Capital Medical University

Beijing, China

RECRUITING

Peking Union Medical College Hospital

Beijing, China

RECRUITING

Peking University First Hospital

Beijing, China

RECRUITING

West China University Hospital

Chengdu, China

RECRUITING

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

Hong Kong, China

RECRUITING

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

RECRUITING

Shanghai Chest Hospital

Shanghai, China

RECRUITING

Shanghai Ninth People's Hospital

Shanghai, China

RECRUITING

The Affiliated Lianyungang Hospital of Xuzhou Medical University

Xuzhou, China

RECRUITING

University of Thessaly

Larissa, Greece

COMPLETED

IRCCS Regina Elena National Cancer Institute

Rome, Italy

RECRUITING

National Defense Medical College

Tokyo, Japan

RECRUITING

Bakirkoy Dr. Sadi Konuk Research and Training Hospital

Bakırköy, Turkey (Türkiye)

RECRUITING

Konya City Hospital

Konya, Turkey (Türkiye)

RECRUITING

Study Officials

  • Daniel I Sessler, MD

    The University of Texas Health Science Center, Houston

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor and Vice President for Clinical and Outcomes Research

Study Record Dates

First Submitted

April 5, 2021

First Posted

May 13, 2021

Study Start

July 25, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

April 25, 2027

Last Updated

August 29, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will share

Each center will retain ownership of its own data. Publication of center-specific data will not be allowed until after the Main Trial Report is published, or two years have elapsed since enrollment of the last patient. The Executive Committee welcomes suggestions for sub-studies based on a partial or the full trial dataset. Sub-studies will be allocated based on importance and novelty of the proposals, and priority will be given to high-enrolling centers. However, all multi-center publications will be on a collaborative basis and include appropriate co-authors. The Executive Committee will do its best to be fair and equitable in assigning sub-studies. Data will be shared with external parties on a collaborative basis with approval of the Executive Committee and appropriate data-use agreements.

Locations