AnesthesiaPhase 4VEGA-1NCT04789330
Norepinephrine vs Phenylephrine During General Anesthesia
A Phase 4 study testing Norepinephrine and Phenylephrine in people with Anesthesia and Surgery, run by University of California, San Francisco at 5 sites in United States.
Trial summary
50 million patients undergo surgery each year in the United States. Postoperative mortality is considered the third leading cause of death worldwide. Hypotension during surgery have been linked to increased postoperative morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Anesthesia, Surgery, Hypotension
- What is being tested?
- Norepinephrine and Phenylephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,626 participants
- Where
- 5 sitesUnited States
- Study dates
- 1 Jul 2021to 1 Apr 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 18 Years and older
- Surgery under general anesthesia and requiring infusion of vasopressors to maintain the mean arterial pressure.
- Surgery duration>2 hours
Who cannot join
- Cardiac surgery
- Patients on ECMO
- Organ transplantation
- Outpatient (come-and-go surgery)
- Obstetric procedures
- Patient already receiving NE or PE before induction of anesthesia
- Patients transferred immediately (i.e. within 24 hours) after surgery to another hospital.
- Patients with severe trauma
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110
UCSF Medical Center at Mount Zion
San Francisco, California, 94115
UCSF Medical Center at Parnassus
San Francisco, California, 94143
UCSF Medical Center at Mission Bay
San Francisco, California, 94158
About this study
Official title: The Choice of Vasopressor for Treating Hypotension During General Anesthesia: a Pilot Pragmatic Cluster Cross-over Randomized Trial (the VEGA-1 Trial)
50 million patients undergo surgery each year in the United States. Postoperative mortality is considered the third leading cause of death worldwide. Hypotension during surgery have been linked to increased postoperative morbidity and mortality. Episodes of hypotension during surgery are associated with an increased risk of acute kidney injury, stroke, cardiac events and death. Treating or preventing hypotension during general anesthesia and major surgery was found to improve outcomes. At this time, it is unclear what is the best vasopressor to maintain blood pressure during surgery under general anesthesia. With this pilot pragmatic trial, the investigators will explore the impact of norepinephrine (NE) or phenylephrine (PE) on post-operative events in patients undergoing major surgery with general anesthesia and needing vasopressors infusion to maintain their systemic arterial pressure.
Read the detailed description
Postoperative mortality is considered the third leading cause of death worldwide. Hemodynamic instability and specifically hypotension during surgery have been linked to increased postoperative morbidity and mortality. Episodes of hypotension during surgery are associated with an increased risk of acute kidney injury, stroke, cardiac events and death. Treating or preventing hypotension during general anesthesia and major surgery was found to improve outcomes. At this time, it is unclear what is the best vasopressor to maintain blood pressure during surgery.
Hypotension during anesthesia and surgery is commonly treated with vasopressors such as phenylephrine (PE), a synthetic pure vasoconstrictor, or norepinephrine (NE), which has both inotropic and vasoconstrictor activity. NE increases cardiac output and increases cardio-vascular coupling due to alpha-agonist effects compared to PE, a purely vasoconstrictive agent.
The investigators hypothesize that norepinephrine will be superior to phenylephrine. The effect size is expected to be modest, therefore requiring a large sample size, and will vary between subgroups determined by patients' individual characteristics.
This pilot trial (VEGA-1) will allow to 1) test the feasibility of the study using a cross-over cluster randomized controlled trial and 2) estimate the effect size of the use of NE or PE on post-operative outcome in the overall population but also investigate the Heterogeneity in Treatment Effect (HTE) of the drugs among subgroups or clusters of patients for designing a larger trial.
Design: pragmatic, cluster-randomized, open-labeled, multiple-crossover trial across hospital from University of California, San Francisco (UCSF) and University of California, Los Angeles (UCLA). Centers will be assigned to use either PE or NE for the first-line intravenous infusion of vasopressor in the OR. Data will be collected in routine clinical care and automatically extracted from the electronic health record (EHR).
Primary endpoint:
- Separation between study groups in the first line vasopressor administration (% of cases with appropriate vasopressor with respect to group attribution).
Secondary endpoints:
- Death within 30 days
- Acute kidney injury defined by the KDIGO definition
- Severe acute kidney injury (stage 2 or 3 of the KDIGO definition)
- Myocardial Injury following non-cardiac surgery (MINS)
- Adverse cardio-renal events
- Hospital length of stay
- Rehospitalization within 30 days
- Conditions
- Anesthesia, Surgery, Hypotension
- Being tested
- Norepinephrine, Phenylephrine
- Keywords
- vasopressor, outcome, AKI, cardiovascular, complications
- Medical subject headings
- Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NorepinephrineDrug
Norepinephrine administered during anesthesia
PhenylephrineDrug
Phenylephrine administered during anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Norepinephrine | Active comparator | Norepinephrine continuous infusion as the first line vasopressor Receives: Drug: Norepinephrine |
| Phenylephrine | Active comparator | Phenylephrine continuous infusion as the first line vasopressor Receives: Drug: Phenylephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Assigned Vasopressor Given
First line vasopressor administration will be measured as a percent of total eligible participants with assigned vasopressor given during anesthesia time, up to 24 hours
Measured: Anesthesia time, up to 24 hours
Secondary outcomes (7)
Number of Participants Who Died Within 30 Days After Surgery
Death within 30 days of surgery.
Measured: 30 days
Number of Participants With Acute Kidney Injury (AKI)
AKI is measured using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine. Acute kidney injury is defined as an increase in serum creatinine ≥ 0.3 mg/dL within 48 hours, or an increase in serum creatinine ≥ 1.5-fold from baseline within 7 days, or initiation of renal replacement therapy within 7 days.
Measured: 7 days
Number of Participants With Severe Acute Kidney Injury
Severe acute kidney injury is assessed using the KDIGO definition based on serum creatinine or need for Renal Replacement Therapy (RRT). Severe Acute Kidney Injury is defined as an increase in serum creatinine ≥ 2-fold from baseline within 7 days, or initiation of renal replacement therapy within 7 days.
Measured: 7 days
Hospital Length of Stay
Days between date of surgery and hospital discharge
Measured: In-hospital, up to 30 days
Number of Participants With Myocardial Injury After Non-cardiac Surgery (MINS)
Number of participants with post-operative myocardial injury defined as a troponin elevation.
Measured: 7 days
Adverse Cardio-renal Events
Number of patients meeting a combined endpoint of AKI and/or MINS
Measured: 7 days
Rehospitalization Within 30 Days
Patients discharge and readmitted for more than 24 hours within 30 days after surgery
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2021
- Study start1 Jul 2021
- Primary completion1 Apr 2022
- Study completion1 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- pragmatic, cluster-randomized, open-labeled, multiple-crossover trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,626 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthieu LEGRAND, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04789330
- Sponsor's protocol ID
- A135759
- Acronym
- VEGA-1
- Status last verified
- Aug 2026
- First submitted
- 4 Mar 2021
- Last updated
- 1 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36925330Krone S, Bokoch MP, Kothari R, Fong N, Tallarico RT, Sturgess-DaPrato J, Pirracchio R, Zarbock A, Legrand M. Association between peripheral perfusion index and postoperative acute kidney injury in major noncardiac surgery patients receiving continuous vasopressors: a post hoc exploratory analysis of the VEGA-1 trial. Br J Anaesth. 2024 Apr;132(4):685-694. doi: 10.1016/j.bja.2023.11.054. Epub 2024 Jan 19.
PubMed 38242802
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Choice of Vasopressor for Treating Hypotension During General Anesthesia: a Pilot Pragmatic Cluster Cross-over Randomized Trial (the VEGA-1 Trial)
- ClinicalTrials.gov ID
- NCT04789330
- Acronym / sponsor ID
- VEGA-1 / A135759
- Conditions
- Anesthesia, Surgery, Hypotension
- Keywords
- vasopressor, outcome, AKI, cardiovascular, complications
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,626 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- 1 Jul 2021 (actual)
- Primary completion
- 1 Apr 2022 (actual)
- Study completion
- 1 Apr 2022 (actual)
- First posted
- 9 Mar 2021 (actual)
- Results
- Posted 18 Dec 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
50 million patients undergo surgery each year in the United States. Postoperative mortality is considered the third leading cause of death worldwide. Hypotension during surgery have been linked to increased postoperative morbidity and mortality. Episodes of hypotension during surgery are associated with an increased risk of acute kidney injury, stroke, cardiac events and death. Treating or preventing hypotension during general anesthesia and major surgery was found to improve outcomes. At this time, it is unclear what is the best vasopressor to maintain blood pressure during surgery under general anesthesia. With this pilot pragmatic trial, the investigators will explore the impact of norepinephrine (NE) or phenylephrine (PE) on post-operative events in patients undergoing major surgery with general anesthesia and needing vasopressors infusion to maintain their systemic arterial pressure.
Detailed description
Postoperative mortality is considered the third leading cause of death worldwide. Hemodynamic instability and specifically hypotension during surgery have been linked to increased postoperative morbidity and mortality. Episodes of hypotension during surgery are associated with an increased risk of acute kidney injury, stroke, cardiac events and death. Treating or preventing hypotension during general anesthesia and major surgery was found to improve outcomes. At this time, it is unclear what is the best vasopressor to maintain blood pressure during surgery.
Hypotension during anesthesia and surgery is commonly treated with vasopressors such as phenylephrine (PE), a synthetic pure vasoconstrictor, or norepinephrine (NE), which has both inotropic and vasoconstrictor activity. NE increases cardiac output and increases cardio-vascular coupling due to alpha-agonist effects compared to PE, a purely vasoconstrictive agent.
The investigators hypothesize that norepinephrine will be superior to phenylephrine. The effect size is expected to be modest, therefore requiring a large sample size, and will vary between subgroups determined by patients' individual characteristics.
This pilot trial (VEGA-1) will allow to 1) test the feasibility of the study using a cross-over cluster randomized controlled trial and 2) estimate the effect size of the use of NE or PE on post-operative outcome in the overall population but also investigate the Heterogeneity in Treatment Effect (HTE) of the drugs among subgroups or clusters of patients for designing a larger trial.
Design: pragmatic, cluster-randomized, open-labeled, multiple-crossover trial across hospital from University of California, San Francisco (UCSF) and University of California, Los Angeles (UCLA). Centers will be assigned to use either PE or NE for the first-line intravenous infusion of vasopressor in the OR. Data will be collected in routine clinical care and automatically extracted from the electronic health record (EHR).
Primary endpoint:
- Separation between study groups in the first line vasopressor administration (% of cases with appropriate vasopressor with respect to group attribution).
Secondary endpoints:
- Death within 30 days
- Acute kidney injury defined by the KDIGO definition
- Severe acute kidney injury (stage 2 or 3 of the KDIGO definition)
- Myocardial Injury following non-cardiac surgery (MINS)
- Adverse cardio-renal events
- Hospital length of stay
- Rehospitalization within 30 days
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- pragmatic, cluster-randomized, open-labeled, multiple-crossover trial
| Arm | Type | Receives |
|---|---|---|
| Norepinephrine | Active comparator | Drug: NorepinephrineNorepinephrine continuous infusion as the first line vasopressor |
| Phenylephrine | Active comparator | Drug: PhenylephrinePhenylephrine continuous infusion as the first line vasopressor |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- age 18 Years and older
- Surgery under general anesthesia and requiring infusion of vasopressors to maintain the mean arterial pressure.
- Surgery duration>2 hours
Key exclusion criteria (8 listed)
- Cardiac surgery
- Patients on ECMO
- Organ transplantation
- Outpatient (come-and-go surgery)
- Obstetric procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NorepinephrineNorepinephrine administered during anesthesia | Drug | Norepinephrine |
| PhenylephrinePhenylephrine administered during anesthesia | Drug | Phenylephrine |
Primary outcome
Number of Participants With Assigned Vasopressor Given
Time frame: Anesthesia time, up to 24 hours
First line vasopressor administration will be measured as a percent of total eligible participants with assigned vasopressor given during anesthesia time, up to 24 hours
7 secondary outcomes
Number of Participants Who Died Within 30 Days After Surgery
Time frame: 30 days
Number of Participants With Acute Kidney Injury (AKI)
Time frame: 7 days
Number of Participants With Severe Acute Kidney Injury
Time frame: 7 days
Hospital Length of Stay
Time frame: In-hospital, up to 30 days
Number of Participants With Myocardial Injury After Non-cardiac Surgery (MINS)
Time frame: 7 days
Adverse Cardio-renal Events
Time frame: 7 days
Rehospitalization Within 30 Days
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 36925330Legrand 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.
- Derived from this study: PubMed 38242802Krone S, Bokoch MP, Kothari R, Fong N, Tallarico RT, Sturgess-DaPrato J, Pirracchio R, Zarbock A, Legrand M. Association between peripheral perfusion index and postoperative acute kidney injury in major noncardiac surgery patients receiving continuous vasopressors: a post hoc exploratory analysis of the VEGA-1 trial. Br J Anaesth. 2024 Apr;132(4):685-694. doi: 10.1016/j.bja.2023.11.054. Epub 2024 Jan 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthieu LEGRAND, MD, PhD principal investigator
University of California, San Francisco
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Norepinephrine and Phenylephrine in people with Anesthesia and Surgery, run by University of California, San Francisco at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Assigned Vasopressor Given (time frame: Anesthesia time, up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04789330, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.