The GUARDIAN Trial - Vasopressor Sub-Study

The University of Texas System (UT)

Status and phase: Invitation-only; Phase 4

Conditions: Blood Pressure

Treatments: Procedure: Routine Blood Pressure Management; Drug: Norepinephrine; Drug: Phenylephrine; Procedure: Tight Blood Pressure Management

Study type: Interventional

Funder types: Other

Identifiers

NCT04934748

HSC-MS-24-1026 (vasopressor)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 6,254 estimated patients

Sex: All

Ages: 45+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

---

6,254 participants in 4 patient groups

Routine Blood Pressure Management with Phenylephrine

Active Comparator group

Description:

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

Treatment:

Drug: Phenylephrine

Procedure: Routine Blood Pressure Management

Routine Blood Pressure Management with Norepinephrine

Active Comparator group

Description:

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

Treatment:

Drug: Norepinephrine

Procedure: Routine Blood Pressure Management

Tight Blood Pressure Management with Phenylephrine

Active Comparator group

Description:

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

Treatment:

Procedure: Tight Blood Pressure Management

Drug: Phenylephrine

Tight Blood Pressure Management with Norepinephrine

Active Comparator group

Description:

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

Treatment:

Procedure: Tight Blood Pressure Management

Drug: Norepinephrine