Norepinephrine vs Phenylephrine During General Anesthesia

Surgery Clinical Trial

— VEGA-1  

Official title:

The Choice of Vasopressor for Treating Hypotension During General Anesthesia: a Pilot Pragmatic Cluster Cross-over Randomized Trial (the VEGA-1 Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04789330
• Other study ID #: A135759
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2021
• Est. completion date: April 1, 2022

Study information

• Verified date: May 2022
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2000
• Est. completion date: April 1, 2022
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• age 18 Years and older

• Surgery under general anesthesia and requiring infusion of vasopressors to maintain the mean arterial pressure.

• Surgery duration>2 hours

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anesthesia
• Hypotension
• Surgery

Intervention

Drug:
• Norepinephrine
Norepinephrine administered during anesthesia
• Phenylephrine
Phenylephrine administered during anesthesia

Locations

Country	Name	City	State
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	UCSF Medical Center at Mission Bay	San Francisco	California
United States	UCSF Medical Center at Mount Zion	San Francisco	California
United States	UCSF Medical Center at Parnassus	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of total cases with assigned vasopressor given	First line vasopressor administration will be measured as a percent of total eligible cases with assigned vasopressor given during anesthesia time, up to 24 hours	Anesthesia time, up to 24 hours
Secondary	Death	Number of participants dying within 30 days after surgery	30 days
Secondary	Acute kidney injury (AKI)	AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine	7 days
Secondary	Severe acute kidney injury	Stage 2 or 3 AKI using the KDIGO definition based on serum creatinine or need for Renal Replacement Therapy (RRT)	7 days
Secondary	Hospital length of stay	Days between date of surgery and hospital discharge	In-hospital, up to 30 days
Secondary	Myocardial Injury after non-cardiac surgery (MINS)	Number of patients with post-operative myocardial injury defined as a troponin elevation	7 days
Secondary	Adverse Cardio-renal events	Number of patients meeting a combined endpoint of AKI and/or MINS	7 days
Secondary	Rehospitalization within 30 days	Patients discharge and readmitted for more than 24 hours within 30 days after surgery	30 days