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

NCT ID: NCT06802224

Last Updated: 2025-04-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 18000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-01
• Study Completion Date: 2028-07-31

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Norepinephrine

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

Group Type: ACTIVE_COMPARATOR

Norepinephrine

Intervention Type: DRUG

Intravenous Norepinephrine for both infusion and bolus dosing

Phenylephrine

Phenylephrine as the first-line intraoperative vasopressor during general anesthesia

Group Type: ACTIVE_COMPARATOR

Phenylephrine

Intervention Type: DRUG

Intravenous Phenylephrine for both infusion and bolus dosing

Interventions

Norepinephrine

Intravenous Norepinephrine for both infusion and bolus dosing

Intervention Type: DRUG

Phenylephrine

Intravenous Phenylephrine for both infusion and bolus dosing

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Henry Ford Health System

OTHER

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: collaborator

University of Maryland

OTHER

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sachin Kheterpal, MD MBA

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Matthieu Legrand, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Allison Janda, MD

Role: STUDY_DIRECTOR

University of Michigan

Michael P Bokoch, MD PhD

Role: STUDY_DIRECTOR

University of California, San Francisco

Locations

University of California, San Francisco

San Francisco, California, United States

Site Status: RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Matthieu Legrand, MD PhD

Role: CONTACT

matthieu.legrand@ucsf.edu

415-476-9035

Michael P. Bokoch, MD PhD

Role: CONTACT

michael.bokoch@ucsf.edu

415-476-8389

Facility Contacts

Michael P Bokoch, MD PhD

Role: primary

michael.bokoch@ucsf.edu

415-476-8389

Niel Panchal, BS

Role: backup

niel.panchal2@ucsf.edu

415-514-1647

Allison Janda, MD

Role: primary

ajanda@med.umich.edu

734-936-4000

Rebecca Pantis

Role: backup

repantis@med.umich.edu

References

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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.

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Other Identifiers

R01DK139484

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23-39683

Identifier Type: -

Identifier Source: org_study_id