Summary

Eligibility
for people ages 18-99 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion
Principal Investigator
by Matthieu LEGRAND, MD, PhD
Photo of Matthieu LEGRAND
Matthieu LEGRAND

Description

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.

Official Title

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

Details

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: - Major adverse cardiovascular and renal events (combined endpoint of death, myocardial infarction, stroke, acute decompensated heart failure and acute kidney injury). - Hospital length of stay - Acute kidney injury defined by the KDIGO definition 20 - Severe acute kidney injury (stage 2 or 3 of the KDIGO definition) - Major adverse kidney events (combined endpoint of death and/or dialysis and/or non recovery from acute kidney injury at hospital discharge). - Surgical complication requiring a new surgical procedure - Rehospitalization within 30 days

Keywords

Anesthesia Surgery Hypotension vasopressor outcome AKI cardiovascular complications Phenylephrine Oxymetazoline Norepinephrine

Eligibility

You can join if…

Open to people ages 18-99

  • age 18 Years and older
  • Surgery under general anesthesia and requiring infusion of vasopressors to maintain the mean arterial pressure.
  • Surgery duration>2 hours

You CAN'T join if...

  • 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

Locations

  • Zuckerberg San Francisco General Hospital accepting new patients
    San Francisco California 94110 United States
  • UCSF Medical Center at Mount Zion accepting new patients
    San Francisco California 94115 United States
  • UCSF Medical Center at Parnassus accepting new patients
    San Francisco California 94143 United States
  • UCSF Medical Center at Mission Bay accepting new patients
    San Francisco California 94158 United States

Lead Scientist at UCSF

  • Matthieu LEGRAND, MD, PhD
    Professor, Anesthesia. Authored (or co-authored) 155 research publications. Research interests: Acute Kidney Injury · Sepsis · Biomarkers · Critical care medicine · Peri-operative Care.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT04789330
Phase
Phase 4
Study Type
Interventional
Last Updated