VEGA-1: Norepinephrine vs Phenylephrine During General Anesthesia

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT04789330

Collaborator

(none)

2,000

Enrollment

Locations

Arms

Actual Duration (Months)

400

Patients Per Site

44.4

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia Surgery Hypotension	Drug: Norepinephrine Drug: Phenylephrine	Phase 4

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

Study Type:

Interventional

Actual Enrollment :

2000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

pragmatic, cluster-randomized, open-labeled, multiple-crossover trialpragmatic, cluster-randomized, open-labeled, multiple-crossover trial

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Jul 1, 2021

Actual Primary Completion Date :

Apr 1, 2022

Actual Study Completion Date :

Apr 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Norepinephrine Norepinephrine continuous infusion as the first line vasopressor	Drug: Norepinephrine Norepinephrine administered during anesthesia
Active Comparator: Phenylephrine Phenylephrine continuous infusion as the first line vasopressor	Drug: Phenylephrine Phenylephrine administered during anesthesia

Arm

Intervention/Treatment

Active Comparator: Norepinephrine

Norepinephrine continuous infusion as the first line vasopressor

Drug: Norepinephrine

Norepinephrine administered during anesthesia

Active Comparator: Phenylephrine

Phenylephrine continuous infusion as the first line vasopressor

Drug: Phenylephrine

Phenylephrine administered during anesthesia

Outcome Measures

Primary Outcome Measures

Percent of total cases with assigned vasopressor given [Anesthesia time, up to 24 hours]
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

Secondary Outcome Measures

Death [30 days]
Number of participants dying within 30 days after surgery
Acute kidney injury (AKI) [7 days]
AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine
Severe acute kidney injury [7 days]
Stage 2 or 3 AKI using the KDIGO definition based on serum creatinine or need for Renal Replacement Therapy (RRT)
Hospital length of stay [In-hospital, up to 30 days]
Days between date of surgery and hospital discharge
Myocardial Injury after non-cardiac surgery (MINS) [7 days]
Number of patients with post-operative myocardial injury defined as a troponin elevation
Adverse Cardio-renal events [7 days]
Number of patients meeting a combined endpoint of AKI and/or MINS
Rehospitalization within 30 days [30 days]
Patients discharge and readmitted for more than 24 hours within 30 days after surgery

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
2	Zuckerberg San Francisco General Hospital	San Francisco	California	United States	94110
3	UCSF Medical Center at Mount Zion	San Francisco	California	United States	94115
4	UCSF Medical Center at Parnassus	San Francisco	California	United States	94143
5	UCSF Medical Center at Mission Bay	San Francisco	California	United States	94158