Purpose

Low blood pressure, also known as hypotension, is very common during major surgery under general anesthesia. Prolonged or severe hypotension can lead to complications such as kidney injury after surgery that slow down patient recovery. Anesthesiologists commonly administer medications called vasopressors to treat low blood pressure during surgery. These medications help raise the blood pressure back up to a safe range. Two vasopressor medications are commonly used for this purpose: norepinephrine and phenylephrine. Each of these medications has slightly different effects on the heart and blood vessels (cardiovascular system). It remains unknown which of these standard medications is better for treating low blood pressure during surgery. The goal of this clinical trial is to determine which of these two medications is better at preventing injury to the kidneys after major noncardiac surgery as well as other complications such as heart problems. Major surgeries are defined as those lasting at least two hours under general anesthesia. This trial will randomize about ten centers in North America to use either norepinephrine or phenylephrine as the primary medication to treat low blood pressure in adults undergoing major noncardiac surgery. Each hospital will prioritize one of the drugs each month, and the assigned drug will rotate each month at each hospital. No further participant involvement will be required as de-identified data are collected as part of standard medical care.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age 18 years or older - Surgery under general anesthesia with a surgery duration of 2 hours or more - Received intravenous vasopressors during surgery

Exclusion Criteria

  • Cardiac surgery - Extra-corporeal membrane oxygenation - Organ transplantation - Obstetric procedures - Procedures on the kidney - Outpatient procedures - Already receiving NE or PE or inotropes before induction of anesthesia (at the time of anesthesia start) - American Society of Anesthesiologists physical status classification 5 or 6 - Patient for whom a local protocol recommends a specific first line vasopressor - Most recent documented estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m^2 or preoperative renal replacement therapy within 60 days before surgery - Patients who do not have a preoperative creatinine value within 60 days before surgery - Alive patients who do not have a postoperative creatinine value

Study Design

Phase
Phase 4
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Intervention Model Description
This is a multicenter, multiple periods, cluster-randomized, crossover trial design in 10 to 12 sites of the Multicenter Perioperative Outcomes Group (MPOG). The randomization at each site will alternate on a monthly basis between the norepinephrine arm and phenylephrine arm. Each cluster will be a different medical center in a different health system in North America. There will be a 2 month run-in at each site, followed by 12 crossover periods with data collection (6 months randomized to PE, 6 months randomized to NE). This cluster randomization aligns with current clinical practice and is therefore more feasible than an individualized randomization. It also enrolls a diverse population representative of the population being treated in the participating centers. This cluster-randomized crossover design increases the power and the ability to show a realistic difference between the two groups through enrollment of a very large number of patients.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Norepinephrine
Norepinephrine as the first-line intraoperative vasopressor during general anesthesia.
  • Drug: Norepinephrine
    Intravenous Norepinephrine for both infusion and bolus dosing
Active Comparator
Phenylephrine
Phenylephrine as the first-line intraoperative vasopressor during general anesthesia
  • Drug: Phenylephrine
    Intravenous Phenylephrine for both infusion and bolus dosing

Recruiting Locations

University of California, San Francisco
San Francisco, California 94143
Contact:
Michael P Bokoch, MD PhD
415-476-8389
michael.bokoch@ucsf.edu

University of Maryland
College Park, Maryland 20742
Contact:
Megan Anders, MD
410-328-4213
manders@som.umaryland.edu

University of Michigan
Ann Arbor, Michigan 48109
Contact:
Allison Janda, MD
734-936-4000
ajanda@med.umich.edu

Henry Ford Health
Detroit, Michigan 48202
Contact:
Mousab M Eteer, MD
989-839-3000
METEER1@hfhs.org

Duke University Medical Center
Durham, North Carolina 27710
Contact:
Michael Manning, MD
859-619-4712
michael.manning@duke.edu

Wake Forest University School of Medicine
Winston-Salem, North Carolina 27101
Contact:
Ashish Khanna, MD
336-716-4498
akhanna@wakehealth.edu

UT Southwestern Medical Center
Dallas, Texas 75390
Contact:
Siddharth Dave, MD
214-645-8300
Siddharth.Dave@UTSouthwestern.edu

University of Virginia
Charlottesville, Virginia 22903
Contact:
Bhiken Naik, MD
434-924-2547
bin4n@uvahealth.org

More Details

Status
Recruiting
Sponsor
University of California, San Francisco

Study Contact

Matthieu Legrand, MD PhD
415-476-9035
matthieu.legrand@ucsf.edu

Detailed Description

VEGA-2 is an open-label, pragmatic, multiple periods, cluster-randomized, crossover trial across hospitals from MPOG. Hospital centers will be assigned to use either phenylephrine (PE) or norepinephrine (NE) for the first-line intravenous vasopressor in the operating room for the treatment of intraoperative hypotension. Centers will be randomly assigned to use PE during even-numbered months and NE during odd-numbered months, or vice versa. Data will be collected from routine clinical care and automatically extracted from the electronic health record. No additional lab tests or procedures will be required for the study. Only the randomization (of each hospital to the sequence of interventions) will be different from usual care. The intervention is the first line vasopressor used for both infusion and bolus dosing, either PE or NE . Anesthesia providers will use the concentration that their respective center already uses in line with local anesthesia and pharmacy standard operating procedures. Anesthesiologists will provide standard of care during the intraoperative period. They will evaluate the need for vasopressors based on hemodynamic assessment and the arterial pressure goals during the procedure. Anesthesia providers will be encouraged to maintain mean arterial pressure above 65 mmHg or within 20% from baseline, but the arterial pressure targets can be adjusted on an individual basis, for instance during pre-surgical time-out, or based on individual assessment. Doses of bolus or continuous infusion of vasopressors will be adjusted to reach these goals on an individual basis. Of note, the anesthesia provider could use the alternative vasopressor if they consider the benefit of one drug being higher. A second line vasopressor will be allowed. The choice of the first line vasopressors will be determined by the randomization block.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.