Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04789330 |
| Other study ID # |
A135759 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| 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 |
| Health authority |
|
| 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
