Norepinephrine vs Phenylephrine for Preventing Acute Kidney Injury

(VEGA-2 Trial)

Recruiting at 1 trial location

Overseen By Michael P. Bokoch, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

Must not be taking: Norepinephrine, Phenylephrine, Inotropes

Disqualifiers: Cardiac surgery, Organ transplantation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: During surgery

18000 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It mainly focuses on the use of specific blood pressure medications during surgery.

What data supports the effectiveness of the drugs norepinephrine and phenylephrine for preventing acute kidney injury?

Research suggests that norepinephrine can be beneficial for kidney function in patients with sepsis by improving urine output, although its effect on overall kidney function is less consistent. Phenylephrine's role in preventing acute kidney injury is less clear, and its use during surgery has been associated with a risk of kidney injury. ^{1 2 3 4 5}

Is norepinephrine or phenylephrine safe for preventing acute kidney injury?

Norepinephrine and phenylephrine are generally considered safe for use in humans, but there are concerns about norepinephrine potentially affecting kidney function due to its impact on blood flow. However, current evidence suggests that norepinephrine is safe and possibly beneficial for kidney health in patients with low blood pressure and acute kidney injury. ^{4 6 7 8 9}

How do norepinephrine and phenylephrine differ from other drugs for preventing acute kidney injury?

Norepinephrine and phenylephrine are unique because they are vasopressors (drugs that tighten blood vessels) used to manage blood pressure, which can affect kidney function. Unlike other treatments, they are specifically being studied for their effects on preventing acute kidney injury by maintaining blood flow during surgery or in conditions like septic shock. ^{3 9 10 11 12}

What is the purpose of this trial?

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.

Research Team

Sachin Kheterpal, MD MBA

Principal Investigator

University of Michigan

Matthieu Legrand, MD PhD

Principal Investigator

University of California, San Francisco

Allison Janda, MD

Principal Investigator

University of Michigan

Michael P Bokoch, MD PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for adults undergoing major noncardiac surgery lasting at least two hours under general anesthesia. It aims to see if certain medications can prevent kidney injury and other complications after surgery.

Inclusion Criteria

I had surgery under general anesthesia that lasted 2 hours or more.

I was given medication to raise my blood pressure during surgery.

Exclusion Criteria

My treatment can be done without staying in the hospital.

Extra-corporeal membrane oxygenation

Obstetric procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either norepinephrine or phenylephrine as the first-line vasopressor during major non-cardiac surgery

During surgery

Intraoperative period

Follow-up

Participants are monitored for acute kidney injury and other complications post-surgery

28 days

Treatment Details

Interventions

• Norepinephrine
• Phenylephrine

Trial Overview The study compares the effectiveness of two vasopressors, norepinephrine and phenylephrine, in preventing postoperative acute kidney injury. Hospitals will alternate monthly between these drugs during surgeries.

Participant Groups

Group I: Norepinephrine Active Control 1 Intervention

Norepinephrine as the first-line intraoperative vasopressor during general anesthesia.

Group II: Phenylephrine Active Control 1 Intervention

Phenylephrine as the first-line intraoperative vasopressor during general anesthesia

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

University of Virginia

Collaborator

Trials

802

Recruited

1,342,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Wake Forest University Health Sciences

Collaborator

Trials

1,432

Recruited

2,506,000+

Henry Ford Health System

Collaborator

Trials

334

Recruited

2,197,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Findings from Research

In a study of 86 pre-eclamptic women undergoing cesarean sections, both phenylephrine and norepinephrine were found to be equally effective in treating postspinal hypotension, with no significant differences in neonatal outcomes as measured by umbilical artery pH.

However, the phenylephrine group experienced fewer hypotensive episodes and lower heart rates compared to the norepinephrine group, suggesting it may be a safer option in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind comparison of phenylephrine and norepinephrine for the management of postspinal hypotension in pre-eclamptic patients undergoing caesarean section. Mohta, M., R, L., Chilkoti, GT., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Vasopressors and the kidney. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of norepinephrine on renal perfusion, filtration and oxygenation in vasodilatory shock and acute kidney injury. [2021]

3. France pubmed.ncbi.nlm.nih.gov

Association of the exclusive use of intraoperative phenylephrine for treatment of hypotension with the risk of acute kidney injury after noncardiac surgery. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Vasoactive drugs and acute kidney injury. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Norepinephrine Administration Is Associated with Higher Mortality in Dialysis Requiring Acute Kidney Injury Patients with Septic Shock. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Association between acute kidney injury and norepinephrine use following cardiac surgery: a retrospective propensity score-weighted analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A randomised double-blind comparison of phenylephrine and norepinephrine for the management of postspinal hypotension in pre-eclamptic patients undergoing caesarean section. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of norepinephrine and a combined norepinephrine and dobutamine infusion on systemic hemodynamics and indices of renal function in normotensive neonatal thoroughbred foals. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Norepinephrine for hypotensive vasodilatation after cardiac surgery: impact on renal function. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial. [2022]

11. India pubmed.ncbi.nlm.nih.gov

Comparison of phenylephrine and norepinephrine in the management of dopamine-resistant septic shock. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Moderate intrarenal vasoconstriction after high pressor doses of norepinephrine in the rat: comparison with effects of angiotensin II. [2022]