Trial Outcomes & Findings for Norepinephrine vs Phenylephrine During General Anesthesia (NCT NCT04789330)

NCT ID: NCT04789330

Last Updated: 2025-12-18

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 3626 participants
• Primary outcome timeframe: Anesthesia time, up to 24 hours
• Results posted on: 2025-12-18

Participant Flow

Over a 6-month period, participating sites were randomized to an alternating sequence of first-line vasopressor use. Three sites were randomized to start with Norepinephrine (NE), and two clinics were randomized to start with Phenylephrine (PE). All five sites used each vasopressor (NE and PE) for 3 months.

To maintain a de-identified dataset, the date of participant enrollment/surgery was not collected. Therefore. the Participant Flow cannot be presented according to the sequence assigned to the sites, as the number of participants enrolled in each site per month was not collected, nor can it be derived. Data are reported according to the total number of participants randomized to NE and PE and sites are not shown as the units assigned to avoid double-counting sites in the Participant Flow.

Participant milestones

Measure	Norepinephrine Continous infusion of Norepinephrine as the first-line vasopressor during anesthesia	Phenylephrine Continuous infusion of phenylephrine as the first-line vasopressor during anesthesia
Overall Study STARTED	1809	1817
Overall Study Site 1	845	815
Overall Study Site 2	302	310
Overall Study Site 3	110	128
Overall Study Site 4	261	289
Overall Study Site 5	291	275
Overall Study COMPLETED	1809	1817
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Norepinephrine vs Phenylephrine During General Anesthesia

Baseline characteristics by cohort

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor	Total n=3626 Participants Total of all reporting groups
Age, Continuous	63 years n=47 Participants	63 years n=41 Participants	63 years n=88 Participants
Sex: Female, Male Female	917 Participants n=47 Participants	908 Participants n=41 Participants	1825 Participants n=88 Participants
Sex: Female, Male Male	892 Participants n=47 Participants	909 Participants n=41 Participants	1801 Participants n=88 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	326 Participants n=47 Participants	308 Participants n=41 Participants	634 Participants n=88 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1440 Participants n=47 Participants	1469 Participants n=41 Participants	2909 Participants n=88 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	43 Participants n=47 Participants	40 Participants n=41 Participants	83 Participants n=88 Participants
Region of Enrollment United States	1809 participants n=47 Participants	1817 participants n=41 Participants	3626 participants n=88 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Number of Participants With Assigned Vasopressor Given	1570 Participants	1627 Participants

SECONDARY outcome

Timeframe: 30 days

Death within 30 days of surgery.

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Number of Participants Who Died Within 30 Days After Surgery	20 Participants	22 Participants

SECONDARY outcome

Timeframe: 7 days

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.

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Number of Participants With Acute Kidney Injury (AKI)	140 Participants	135 Participants

SECONDARY outcome

Timeframe: 7 days

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.

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Number of Participants With Severe Acute Kidney Injury	28 Participants	31 Participants

SECONDARY outcome

Timeframe: In-hospital, up to 30 days

Days between date of surgery and hospital discharge

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Hospital Length of Stay	4 days Interval 2.1 to 7.0	4.1 days Interval 2.1 to 7.5

SECONDARY outcome

Timeframe: 7 days

Number of participants with post-operative myocardial injury defined as a troponin elevation.

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Number of Participants With Myocardial Injury After Non-cardiac Surgery (MINS)	44 Participants	38 Participants

SECONDARY outcome

Timeframe: 7 days

Number of patients meeting a combined endpoint of AKI and/or MINS

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Adverse Cardio-renal Events	168 Participants	159 Participants

SECONDARY outcome

Timeframe: 30 days

Patients discharge and readmitted for more than 24 hours within 30 days after surgery

Outcome measures

Measure	Norepinephrine n=1809 Participants Norepinephrine continuous infusion as the first-line vasopressor	Phenylephrine n=1817 Participants Phenylephrine continuous infusion as the first-line vasopressor
Rehospitalization Within 30 Days	56 Participants	66 Participants

Adverse Events

Norepinephrine

Serious events: 20 serious events

Other events: 168 other events

Deaths: 20 deaths

Phenylephrine

Serious events: 22 serious events

Other events: 159 other events

Deaths: 22 deaths

Serious adverse events

Measure	Norepinephrine n=1809 participants at risk Norepinephrine continuous infusion as the first line vasopressor Norepinephrine: Norepinephrine administered during anesthesia	Phenylephrine n=1817 participants at risk Phenylephrine continuous infusion as the first line vasopressor Phenylephrine: Phenylephrine administered during anesthesia
Cardiac disorders mortality	1.1% 20/1809 • Number of events 20 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.	1.2% 22/1817 • Number of events 22 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.

Other adverse events

Measure	Norepinephrine n=1809 participants at risk Norepinephrine continuous infusion as the first line vasopressor Norepinephrine: Norepinephrine administered during anesthesia	Phenylephrine n=1817 participants at risk Phenylephrine continuous infusion as the first line vasopressor Phenylephrine: Phenylephrine administered during anesthesia
Renal and urinary disorders Acute Kidney Injury	7.7% 140/1809 • Number of events 140 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.	7.4% 135/1817 • Number of events 135 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.
Cardiac disorders Myocardial injury	2.4% 44/1809 • Number of events 44 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.	2.1% 38/1817 • Number of events 38 • Mortality was collected until 30 days post-surgery, and other adverse events were collected until 7 days post-surgery.

Additional Information

Matthieu LEGRAND MD, PhD

University of California, San Francisco

Phone: 415-885-7388

Email: matthieu.legrand@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place