The GUARDIAN Trial - Vasopressor Sub-Study

NCT ID: NCT04934748

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

ENROLLING_BY_INVITATION

Clinical Phase

PHASE4

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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This is a sub-study of the overall GUARDIAN trial (NCT04884802) in which some GUARDIAN trial participants will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Detailed Description

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Participants in the underlying GUARDIAN trial (NCT04884802) will be randomized to: 1) norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management (routine pressure management). Participants in this sub-study will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Conditions

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Blood Pressure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Routine Blood Pressure Management with Phenylephrine

Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Group Type ACTIVE_COMPARATOR

Routine Blood Pressure Management

Intervention Type PROCEDURE

Routine blood pressure control.

Phenylephrine

Intervention Type DRUG

Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Routine Blood Pressure Management with Norepinephrine

Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Group Type ACTIVE_COMPARATOR

Routine Blood Pressure Management

Intervention Type PROCEDURE

Routine blood pressure control.

Norepinephrine

Intervention Type DRUG

Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Tight Blood Pressure Management with Phenylephrine

TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial

Group Type ACTIVE_COMPARATOR

Tight Blood Pressure Management

Intervention Type PROCEDURE

Tight blood pressure control.

Phenylephrine

Intervention Type DRUG

Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Tight Blood Pressure Management with Norepinephrine

Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Group Type ACTIVE_COMPARATOR

Tight Blood Pressure Management

Intervention Type PROCEDURE

Tight blood pressure control.

Norepinephrine

Intervention Type DRUG

Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Interventions

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Routine Blood Pressure Management

Routine blood pressure control.

Intervention Type PROCEDURE

Tight Blood Pressure Management

Tight blood pressure control.

Intervention Type PROCEDURE

Phenylephrine

Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Intervention Type DRUG

Norepinephrine

Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Intervention Type DRUG

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

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

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Main Campus

Cleveland, Ohio, United States

Site Status

Beijing Shijitan Hospital, Capital Medical University

Beijing, , China

Site Status

Peking Union Medical College Hospital

Beijing, , China

Site Status

Shanghai Ninth People's Hospital

Shanghai, , China

Site Status

Shanghai Chest Hospital

Shanghai, , China

Site Status

West China Hospital

Sichuan, , China

Site Status

University of Thessaly

Larissa, , Greece

Site Status

National Defense College

Tokyo, , Japan

Site Status

Countries

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United States China Greece Japan

Other Identifiers

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HSC-MS-24-1026 (vasopressor)

Identifier Type: -

Identifier Source: org_study_id

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