The Choice of Vasopressor to Prevent Postoperative Acute Kidney Injury After Major Non-Cardiac Surgery (VEGA-2)

May 20, 2026 updated by: University of California, San Francisco

Norepinephrine vs Phenylephrine as the First-line Vasopressor to Prevent Postoperative Acute Kidney Injury After Major Non-cardiac Surgery

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

18000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • University Health Network
        • Contact:
        • Principal Investigator:
          • Tariq Esmail, MD
  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Sub-Investigator:
          • Michael P Bokoch, MD PhD
        • Principal Investigator:
          • Matthieu Legrand, MD PhD
        • Contact:
    • Maryland
      • College Park, Maryland, United States, 20742
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan
        • Principal Investigator:
          • Sachin Kheterpal, MD, MBA
        • Sub-Investigator:
          • Allison Janda, MD
        • Contact:
        • Contact:
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health
        • Contact:
        • Contact:
        • Principal Investigator:
          • Mousab M Eteer, MD
    • North Carolina
      • Durham, North Carolina, United States, 27710
      • Winston-Salem, North Carolina, United States, 27101
        • Recruiting
        • Wake Forest University School of Medicine
        • Contact:
        • Principal Investigator:
          • Ashish Khanna, MD
        • Contact:
    • Texas
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
        • Principal Investigator:
          • Bhiken Naik, MD
        • Contact:
        • Contact:
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
        • Principal Investigator:
          • Karen B Domino, MD
        • Sub-Investigator:
          • Wil Van Cleve, MD
        • Sub-Investigator:
          • John Lang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury (AKI)
Time Frame: 7 days
AKI will be defined by the change of serum creatinine based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria.
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Adverse Kidney Events (MAKE)
Time Frame: 28 days
The composite of severe AKI (i.e. stage 2 or 3 AKI based on the KDIGO creatinine-based definition), absence of renal recovery, and/or death.
28 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Myocardial Injury after Noncardiac Surgery (MINS)
Time Frame: 28 days
Elevated cardiac normal or high-sensitivity troponin.
28 days
Hospital length of stay
Time Frame: 28 days
Number of days of inpatient admission.
28 days
Hypotension
Time Frame: During anesthesia care
Mean arterial pressure less than 65 mmHg for at least 15 cumulative minutes.
During anesthesia care
Duration of hypotension
Time Frame: During anesthesia care
The cumulative number of minutes with mean arterial pressure less than 65 mmHg.
During anesthesia care
Severe hypotension
Time Frame: During anesthesia care
Mean arterial pressure less than 55 mmHg for at least 15 cumulative minutes.
During anesthesia care
Duration of severe hypotension
Time Frame: During anesthesia care
The cumulative number of minutes with mean arterial pressure less than 55 mmHg.
During anesthesia care

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

University Health Network, Toronto
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Maryland
University of Michigan
Duke University
Wake Forest University Health Sciences
University of Washington
University of Texas Southwestern Medical Center
Henry Ford Health System
University of Virginia

Investigators

  • Study Director: Allison Janda, MD, University of Michigan
  • Principal Investigator: Sachin Kheterpal, MD MBA, University of Michigan
  • Principal Investigator: Matthieu Legrand, MD PhD, University of California, San Francisco
  • Study Director: Michael P Bokoch, MD PhD, University of California, San Francisco
  • Study Director: Douglas Colquhoun, MB ChB, MSc, MPH, University of Michigan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2025

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2028

Study Registration Dates

First Submitted

January 28, 2025

First Submitted That Met QC Criteria

January 28, 2025

First Posted (Actual)

January 31, 2025

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-39683
  • R01DK139484 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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