# The choice of vasopressor to prevent postoperative acute kidney injury after major non-cardiac surgery: a multicenter pragmatic cluster cross-over randomized trial (the VEGA-2 trial)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $675,175

## Abstract

PRINCIPAL INVESTIGATOR (LAST, FIRST, MIDDLE): Legrand, Matthieu
TITLE OF PROPOSED STUDY: The choice of vasopressors to prevent
postoperative acute kidney injury after major non-cardiac surgery: a multicenter
pragmatic cluster cross-over randomized trial (the VEGA-2 trial)
Title ( max 81 characters )
Norepinephrine vs Phenylephrine for preventing postoperative acute kidney injury
Abstract (30 lines)
Around 50 million patients have surgery every year in the United States. Postoperative acute
kidney injury (PO-AKI) is a major complication after surgery, occurring in 10 to 40% of cases
after major surgery. PO-AKI is associated with higher risk of chronic kidney disease,
cardiovascular events, prolonged hospitalization, higher costs, and mortality. Prevention of PO-
AKI is considered a major outcome in perioperative medicine. Intraoperative hypotension has been
repeatedly associated with an increased risk of PO-AKI and hypotension is a major contributing
factor to PO-AKI. Prevention of hypotension is recommended to decrease the risk of PO-AKI.
Vasopressors are the key pharmacologic intervention for the management of hypotension due to
vasodilation induced by general anesthesia or the systemic inflammation triggered by the surgery.
Phenylephrine and norepinephrine are the two most common intravenous vasopressors used for
this purpose. However, the optimal choice of vasopressor to treat hypotension during surgery under
general anesthesia is unknown. Phenylephrine is a pure alpha-1 agonist (vasoconstrictor), whereas
norepinephrine has both alpha- and beta-adrenergic effects (vasoconstrictor/inotrope).
Norepinephrine increases cardiac output and cardiovascular coupling and decreases inflammation-
induced vascular permeability. Norepinephrine increases renal blood flow in vasodilatory shock.
While several experts have recommended using norepinephrine as the first line vasopressor,
randomized trials are missing, preventing to draw strong recommendations. Given the number of
patients undergoing major non-cardiac surgery under anesthesia in the United States each year and
the burden of PO-AKI, this is a major unaddressed question. We propose to perform a multicenter
cluster-randomized, open-labeled, multiple-crossover trial of phenylephrine versus norepinephrine
as the first-line infusion vasopressor in adult patients undergoing non-cardiac surgery with general
anesthesia within the Multicenter Perioperative Outcomes Group (MPOG). This trial follows a
pilot cluster-randomized trial (VEGA-1 trial, NCT04789330) that showed the feasibility of the
trial in enrolling 3626 patients and provided key preliminary data. This study will provide the
highest level of evidence regarding the best vasopressor to use and perfectly aligns with the
mission of NIDDK to prevent kidney disease and improve health in the surgical population. This
evidence generated by this trial will inform clinical guidelines and ultimately impact patient
outcomes.
VEGA-2 M.Legrand June 2023
1

## Key facts

- **NIH application ID:** 10860868
- **Project number:** 1R01DK139484-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** SACHIN KHETERPAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $675,175
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860868

## Citation

> US National Institutes of Health, RePORTER application 10860868, The choice of vasopressor to prevent postoperative acute kidney injury after major non-cardiac surgery: a multicenter pragmatic cluster cross-over randomized trial (the VEGA-2 trial) (1R01DK139484-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10860868. Licensed CC0.

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