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

NCT06802224 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 23-39683R01DK139484
• Study Type: interventional
• Target: 18,000
• Locations: 2 countries
• Sites: 10

Brief Summary

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

Anesthesia; Surgery With General Anesthesia; Noncardiac Surgery; Hypotension During Surgery; Acute Kidney Injury (AKI); Vasopressor; Myocardial Injury After Noncardiac Surgery (MINS)

Keywords

Norepinephrine; Phenylephrine; Major adverse kidney events; Pragmatic; Cluster randomized; Crossover

Outcome Measures

Primary Outcomes (1)

• Acute Kidney Injury (AKI)

  AKI will be defined by the change of serum creatinine based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

  7 days

Secondary Outcomes (1)

• Major Adverse Kidney Events (MAKE)

  28 days

Other Outcomes (6)

• Myocardial Injury after Noncardiac Surgery (MINS)

  28 days

• Hospital length of stay

  28 days

• Hypotension

  During anesthesia care

Study Arms (2)

Norepinephrine

ACTIVE COMPARATOR

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

Drug: Norepinephrine

Phenylephrine

ACTIVE COMPARATOR

Phenylephrine as the first-line intraoperative vasopressor during general anesthesia

Drug: Phenylephrine

Interventions

Norepinephrine DRUG

Intravenous Norepinephrine for both infusion and bolus dosing

Norepinephrine

Phenylephrine DRUG

Intravenous Phenylephrine for both infusion and bolus dosing

Phenylephrine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (10)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Maryland

College Park, Maryland, 20742, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Health

Detroit, Michigan, 48202, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27101, United States

RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22903, United States

RECRUITING

University of Washington

Seattle, Washington, 98195, United States

RECRUITING

University Health Network

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

Related Publications (9)

• Chiu C, Fong N, Lazzareschi D, Mavrothalassitis O, Kothari R, Chen LL, Pirracchio R, Kheterpal S, Domino KB, Mathis M, Legrand M. Fluids, vasopressors, and acute kidney injury after major abdominal surgery between 2015 and 2019: a multicentre retrospective analysis. Br J Anaesth. 2022 Sep;129(3):317-326. doi: 10.1016/j.bja.2022.05.002. Epub 2022 Jun 8.

  PMID: 35688657 BACKGROUND

• Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.

  PMID: 28973220 BACKGROUND

• Pancaro C, Shah N, Pasma W, Saager L, Cassidy R, van Klei W, Kooij F, Vittali D, Hollmann MW, Kheterpal S, Lirk P. Risk of Major Complications After Perioperative Norepinephrine Infusion Through Peripheral Intravenous Lines in a Multicenter Study. Anesth Analg. 2020 Oct;131(4):1060-1065. doi: 10.1213/ANE.0000000000004445.

  PMID: 32925324 BACKGROUND

• Prowle JR, Forni LG, Bell M, Chew MS, Edwards M, Grams ME, Grocott MPW, Liu KD, McIlroy D, Murray PT, Ostermann M, Zarbock A, Bagshaw SM, Bartz R, Bell S, Bihorac A, Gan TJ, Hobson CE, Joannidis M, Koyner JL, Levett DZH, Mehta RL, Miller TE, Mythen MG, Nadim MK, Pearse RM, Rimmele T, Ronco C, Shaw AD, Kellum JA. Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative. Nat Rev Nephrol. 2021 Sep;17(9):605-618. doi: 10.1038/s41581-021-00418-2. Epub 2021 May 11.

  PMID: 33976395 BACKGROUND

• Mets B. Should Norepinephrine, Rather than Phenylephrine, Be Considered the Primary Vasopressor in Anesthetic Practice? Anesth Analg. 2016 May;122(5):1707-14. doi: 10.1213/ANE.0000000000001239. No abstract available.

  PMID: 27101504 BACKGROUND

• Legrand M, Zarbock A. Ten tips to optimize vasopressors use in the critically ill patient with hypotension. Intensive Care Med. 2022 Jun;48(6):736-739. doi: 10.1007/s00134-022-06708-y. Epub 2022 May 3. No abstract available.

  PMID: 35504977 BACKGROUND

• Mathis MR, Naik BI, Freundlich RE, Shanks AM, Heung M, Kim M, Burns ML, Colquhoun DA, Rangrass G, Janda A, Engoren MC, Saager L, Tremper KK, Kheterpal S, Aziz MF, Coffman T, Durieux ME, Levy WJ, Schonberger RB, Soto R, Wilczak J, Berman MF, Berris J, Biggs DA, Coles P, Craft RM, Cummings KC, Ellis TA 2nd, Fleishut PM, Helsten DL, Jameson LC, van Klei WA, Kooij F, LaGorio J, Lins S, Miller SA, Molina S, Nair B, Paganelli WC, Peterson W, Tom S, Wanderer JP, Wedeven C; Multicenter Perioperative Outcomes Group Investigators. Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury. Anesthesiology. 2020 Mar;132(3):461-475. doi: 10.1097/ALN.0000000000003063.

  PMID: 31794513 BACKGROUND

• Salmasi V, Maheshwari K, Yang D, Mascha EJ, Singh A, Sessler DI, Kurz A. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis. Anesthesiology. 2017 Jan;126(1):47-65. doi: 10.1097/ALN.0000000000001432.

  PMID: 27792044 BACKGROUND

• Legrand M, Kothari R, Fong N, Palaniappa N, Boldt D, Chen LL, Kurien P, Gabel E, Sturgess-DaPrato J, Harhay MO, Pirracchio R, Bokoch MP; VEGA-1 trial investigators. Norepinephrine versus phenylephrine for treating hypotension during general anaesthesia in adult patients undergoing major noncardiac surgery: a multicentre, open-label, cluster-randomised, crossover, feasibility, and pilot trial. Br J Anaesth. 2023 May;130(5):519-527. doi: 10.1016/j.bja.2023.02.004. Epub 2023 Mar 14.

  PMID: 36925330 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Norepinephrine; Phenylephrine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Sachin Kheterpal, MD MBA

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Matthieu Legrand, MD PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Allison Janda, MD

  University of Michigan

  STUDY DIRECTOR

• Michael P Bokoch, MD PhD

  University of California, San Francisco

  STUDY DIRECTOR

• Douglas Colquhoun, MB ChB, MSc, MPH

  University of Michigan

  STUDY DIRECTOR

Central Study Contacts

Matthieu Legrand, MD PhD

CONTACT

415-476-9035; matthieu.legrand@ucsf.edu

Michael P. Bokoch, MD PhD

CONTACT

415-476-8389; michael.bokoch@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 28, 2025
• First Posted: January 31, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 26, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); CA (1)