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Norepinephrine vs Phenylephrine During General Anesthesia (VEGA-1)

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ClinicalTrials.gov Identifier: NCT04789330
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

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:

  • 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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: pragmatic, 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 : July 1, 2021
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : May 2022


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




Primary Outcome Measures :
  1. Percent of total cases 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 cases with assigned vasopressor given during anesthesia time, up to 24 hours


Secondary Outcome Measures :
  1. Major adverse cardiovascular and renal events [ Time Frame: 30 days ]
    Number of participants experiencing a major cardiovascular and/or renal event will be reported as a combined endpoint

  2. Hospital length of stay [ Time Frame: In-hospital, up to 30 days ]
    Days between date of surgery and hospital discharge

  3. Acute kidney injury (AKI) [ Time Frame: 7 days ]
    AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine

  4. Severe acute kidney injury [ Time Frame: 7 days ]
    Stage 2 or 3 AKI using the KDIGO definition based on serum creatinine or need for Renal Replacement Therapy (RRT)

  5. Surgical complication requiring a new surgical procedure [ Time Frame: 30 days ]
    Patient requiring recurrent surgery

  6. Rehospitalization within 30 days [ Time Frame: 30 days ]
    Patients discharge and readmitted for more than 24 hours within 30 days after surgery



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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04789330


Contacts
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Contact: Matthieu LEGRAND, MD, PhD 4155143781 matthieu.legrand@ucsf.edu
Contact: Michael BOKOCH, MD, PhD 4155143781 michael.bokoch@ucsf.edu

Locations
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United States, California
Ronald Reagan UCLA Medical Center Not yet recruiting
Los Angeles, California, United States, 90095
Contact: David Boldt, MD         
Zuckerberg San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Nandini Palaniappa, MD         
UCSF Medical Center at Mount Zion Recruiting
San Francisco, California, United States, 94115
Contact: Christy Ingllis-Arkell, MD         
UCSF Medical Center at Parnassus Recruiting
San Francisco, California, United States, 94143
Contact: Michael Bokoch, MD         
UCSF Medical Center at Mission Bay Recruiting
San Francisco, California, United States, 94158
Contact: Lee-Lynn Chen, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
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Principal Investigator: Matthieu LEGRAND, MD, PhD University of California, San Francisco
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04789330    
Other Study ID Numbers: A135759
First Posted: March 9, 2021    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of California, San Francisco:
vasopressor
outcome
AKI
cardiovascular
complications
Additional relevant MeSH terms:
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Hypotension
Vascular Diseases
Cardiovascular Diseases
Phenylephrine
Oxymetazoline
Norepinephrine
Cardiotonic Agents
Mydriatics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sympathomimetics
Vasoconstrictor Agents
Nasal Decongestants
Respiratory System Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents