Clinical trial NCT04934748: GUARDIAN (NCT04884802) Sub-study, Phenylephrine v. Norepinephrine
Official title: GUARDIAN (NCT04884802) Sub-study Comparing Phenylephrine and Norepinephrine
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE4
Conditions: Blood Pressure
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2021-06-22
Enrollment: 6254
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

Brief summary: Some patients participating in the underlying GUARDIAN trial (NCT04884802) will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Detailed description: Patients participating 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). Patients participating in this sub-study will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.

Eligibility criteria: Inclusion Criteria:

* 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);
* Chronically taking at least one anti-hypertensive medication;
* 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 surgery;
* History of coronary artery disease;
* History of stroke or transient ischemic attack;
* Serum creatinine \>175 µmol/L (\>2.0 mg/dl);
* Diabetes requiring medication;
* Current smoking or 15 pack-year history of smoking tobacco;
* Scheduled for major vascular surgery;
* Body mass index ≥35 kg/m2;
* Preoperative high-sensitivity troponin T \>14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay),77 19 ng/L (Siemens assay, \[Borges, unpublished\]), or 25% of the 99% percentile for other assays;
* B-type natriuretic protein (BNP) \>80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) \>200 ng/L.78,79

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Composite of major perfusion-related complications
timeFrame: 30 days after major non-cardiac surgery
Secondary outcomes:
measure: Postoperative delirium
timeFrame: 4 Postoperative hospital days
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Daniel I Sessler, MD
role: STUDY_CHAIR
References: