The GUARDIAN Trial - Vasopressor Sub-Study

Phase 4

• Conditions: Blood Pressure
• Interventions: Procedure: Routine Blood Pressure Management; Procedure: Tight Blood Pressure Management; Drug: Phenylephrine; Drug: Norepinephrine

• Registration Number: NCT04934748
• Lead Sponsor: The University of Texas Health Science Center, Houston

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-06-14
• Study First Submitted QC: 2021-06-15
• Study First Posted: 2021-06-22
• Study Start: 2021-07-25
• Status Verified: 2025-07
• Last Update Submitted: 2025-08-23
• Last Update Posted: 2025-08-29
• Primary Completion: 2026-12-31
• Study Completion: 2027-04-25

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 6254

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Routine Blood Pressure Management with Phenylephrine	Routine Blood Pressure Management	Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Routine Blood Pressure Management with Phenylephrine	Phenylephrine	Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Routine Blood Pressure Management with Norepinephrine	Routine Blood Pressure Management	Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Routine Blood Pressure Management with Norepinephrine	Norepinephrine	Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Tight Blood Pressure Management with Phenylephrine	Tight Blood Pressure Management	TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Tight Blood Pressure Management with Phenylephrine	Phenylephrine	TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial
Tight Blood Pressure Management with Norepinephrine	Tight Blood Pressure Management	Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
Tight Blood Pressure Management with Norepinephrine	Norepinephrine	Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Primary Outcome Measures

Name	Time	Method
Number of Participants with a Composite of Major Perfusion-Related Complications	During the initial 30 days after major non-cardiac surgery	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.

Trial Locations

Locations (11)

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

MetroHealth Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Fairview Hospital; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States

Beijing Shijitan Hospital, Capital Medical University; 🇨🇳 Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

Shanghai Ninth People's Hospital; 🇨🇳 Shanghai, China

Shanghai Chest Hospital; 🇨🇳 Shanghai, China

West China Hospital; 🇨🇳 Sichuan, China

University of Thessaly; 🇬🇷 Larissa, Greece

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