Norepinephrine vs Phenylephrine During General Anesthesia (VEGA-1)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04789330|
Recruitment Status : Recruiting
First Posted : March 9, 2021
Last Update Posted : July 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Anesthesia Surgery Hypotension||Drug: Norepinephrine Drug: Phenylephrine||Phase 4|
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).
- Separation between study groups in the first line vasopressor administration (% of cases with appropriate vasopressor with respect to group attribution).
- 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
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||2000 participants|
|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|
Active Comparator: Norepinephrine
Norepinephrine continuous infusion as the first line vasopressor
Norepinephrine administered during anesthesia
Active Comparator: Phenylephrine
Phenylephrine continuous infusion as the first line vasopressor
Phenylephrine administered during anesthesia
- 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
- 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
- Hospital length of stay [ Time Frame: In-hospital, up to 30 days ]Days between date of surgery and hospital discharge
- Acute kidney injury (AKI) [ Time Frame: 7 days ]AKI using the Kidney Disease: Improving Global Outcomes (KDIGO) definition based on serum creatinine
- 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)
- Surgical complication requiring a new surgical procedure [ Time Frame: 30 days ]Patient requiring recurrent surgery
- Rehospitalization within 30 days [ Time Frame: 30 days ]Patients discharge and readmitted for more than 24 hours within 30 days after surgery
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
|Contact: Matthieu LEGRAND, MD, PhDfirstname.lastname@example.org|
|Contact: Michael BOKOCH, MD, PhDemail@example.com|
|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|
|Principal Investigator:||Matthieu LEGRAND, MD, PhD||University of California, San Francisco|