Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06129188 |
| Other study ID # |
IRB-300011945 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
July 2024 |
| Est. completion date |
March 2025 |
Study information
| Verified date |
April 2024 |
| Source |
University of Alabama at Birmingham |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The objective of this proposal is to conduct a prospective randomized study comparing the
utility of sedating patients undergoing transesophageal echocardiographic studies with a
novel, recently-FDA-approved sedative agent, remimazolam, versus the sedative used in our
current practice at UAB, propofol. This study will investigate whether remimazolam offers any
benefit over current care vis-à-vis hemodynamics or efficiency/throughput.
This study will be conducted at the University of Alabama at Birmingham. All outpatients and
inpatients scheduled for elective/non-emergent TEE in the UAB Heart and Vascular Center TEE
lab will be considered for enrollment.
Description:
Patients often undergo procedures outside of traditional operating rooms. With continued
advances in minimally invasive and percutaneous techniques, recent trends demonstrate that
sicker and increasingly unstable patients are routinely undergoing progressively more complex
procedures in this space. Many of these procedures and patients necessitate varying levels of
sedation due to pain, anxiety, and optimized procedural-conditions, among other reasons.
Commonly utilized medications include benzodiazepines (like midazolam), opioids (like
fentanyl), sedative-hypnotics (like propofol), and other adjuncts (such as dexmedetomidine
and diphenhydramine).
Previous studies have shown that each of these agents has significant drawbacks that limit
its utility. Propofol, while being fast in onset and offset, is limited by the lack of
available reversal agent, the high liability for significant cardiac and/or respiratory
depression, and the costly requirement of an anesthesia team for administration. Midazolam
does not suffer from any of the shortcomings of propofol, but it has a much slower onset and
offset, limiting both procedural and PACU timeliness/throughput and imparting prolonged CNS
effects on patients (especially older patients) for hours to days after administration. Most
adjuncts similarly have very slow onset and offset profiles, and they necessitate concomitant
administration of other agents to achieve suitable procedural conditions.
Recently, a novel benzodiazepine (remimazolam) received FDA approval for procedural sedation
for procedures lasting no more than thirty minutes. This agent combines the best qualities of
propofol and midazolam while avoiding the downfalls of each. Specifically, remimazolam
appears to maintain hemodynamic stability while rapidly allowing for ideal sedation
conditions without lingering effects. These qualities make it a particularly good choice for
procedural sedation and monitored anesthesia care for sicker, more tenuous patients. Despite
FDA approval, adoption of this agent remains limited at present, likely due in part to cost
as well as limited provider (anesthesiologist & proceduralist) experience with the agent.
Nonetheless, it appears that using remimazolam for procedural sedation for our sickest
patients with the most tenuous hemodynamic status may be a safer alternative to the current
standard of care.
In attempt to answer this question, the investigators wish to compare the current practice of
using propofol for sedation with the sedation achieved using remimazolam at recommended doses
in patients scheduled to undergo transesophageal echocardiography. This patient population
was intentionally chosen as it represents the sickest and most hemodynamically tenuous group
of patients we sedate for procedures.
The significance of the study is that remimazolam, based on published experiences in other
procedures, should produce robust sedation in subjects undergoing transesophageal
echocardiogram studies with significantly less hemodynamic perturbation (hypotension) than
results from propofol as part of current practice. If this observation is confirmed in this
population, then it is likely that a change in the current practice would occur to improve
patient safety.
Purpose: The purpose of this proposal is to conduct a prospective randomized study comparing
the utility and safety of sedating patients for transesophageal echocardiographic studies
with a novel, recently-FDA-approved sedative agent (remimazolam) versus the utility and
safety of sedation produced by propofol.
Primary Hypothesis: Remimazolam will produce sedation for TEE procedures that is similar to
that produced by propofol in terms of sedative conditions and speed of sedation onset/offset
but will be associated with less hypotension.
Outline of Study:
The proposed study is a prospective randomized clinical study. All patients who undergo TEE
already receive anesthesia care team-administered intravenous sedation during their
procedures. In the present study, all groups will continue to receive standard-of-care
treatment but will be randomized using a randomization generator to receive one of two
different FDA-approved pharmacologic agents to achieve this sedation: remimazolam (a recently
FDA-approved sedative hypnotic agent) and propofol (which is the agent most utilized in our
practice). Baseline data collection in patients scheduled for elective/non-emergent inpatient
or outpatient transesophageal echocardiogram will be collected. All physiologic variables
(hemodynamic and respiratory parameters, body temperature, etc.) will be measured continually
and recorded directly in the anesthesia procedure record. Similarly, all input/output data
including any non-study medication administration (including but not limited to sedation and
pressor agents), ongoing fluid, colloid and blood product administration will be recorded in
the anesthesia record.
Assessment of the achieved level of sedation will be performed using the previously-validated
Modified Observer's Assessment of Alertness/Sedation (MOAA/S) technique. Time to return to
baseline neurologic status will be measured using the Modified Aldrete Scoring system as well
as time from procedure finish to sign-out from the post anesthesia care unit by anesthesia
providers.
Results from patients receiving remimazolam sedation will be compared to data from patients
who receive propofol sedation. Since remimazolam will be new to the investigators'
institution, there will be an option for the treating physician to convert their sedation
plan from remimazolam to the more commonly utilized propofol if they do not feel the sedation
is adequate. This will be an intention to treat (ITT) analysis.
Primary endpoints or outcomes: The primary endpoint will be the hemodynamic measures obtained
throughout the transesophageal echocardiogram procedure. Secondary outcomes include a
clinician assessment of the quality of the sedation, duration of onset of sedation, level of
sedation, procedure duration, recovery duration, hemodynamic stability, required pressor use,
complication rate, ICU stay, hospital stay, and 28- and 60-day mortality.
The investigators expect that patients will successfully be able to undergo a transesophageal
echocardiogram using either remimazolam or propofol as a sole agent for sedation. The
investigators expect that sedation conditions and speed of sedation onset and offset will be
similar between the two groups. Most importantly, the investigators expect that there will be
improved hemodynamic stability with use of remimazolam versus propofol (e.g., reduced
hypotension and/or pressor requirement). The data collection, as proposed, should allow for
all these comparisons in a statistically robust fashion.
