Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01219881 |
| Other study ID # |
2010H0174 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
September 2010 |
| Est. completion date |
October 2012 |
Study information
| Verified date |
October 2021 |
| Source |
Ohio State University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a single-center, prospective, randomized, double-blind, double-arm trial including 68
subjects scheduled to undergo urological cystoscope surgeries under general anesthesia (GA)
with intubation through a laryngeal mask airway (LMA) at The Ohio State University Medical
Center (OSUMC). Double blinding will be based on both the subject and the research staff
being unaware of which trial arm the subject is randomized into. Eligible subjects that
provide voluntary and written informed consent will be included in this study.
Description:
This is a single-center, prospective, randomized, double-blind, double-arm trial including 68
subjects scheduled to undergo urological cystoscope surgeries under general anesthesia (GA)
with intubation through a laryngeal mask airway (LMA) at The Ohio State University Medical
Center (OSUMC). Double blinding will be based on both the subject and the research staff
being unaware of which trial arm the subject is randomized into. Eligible subjects that
provide voluntary and written informed consent will be included in this study.
Day -14 to 0
Subjects will undergo screening procedures up to 14 days prior to administration of study
treatment. The research staff will collect the subjects' medical history (including reason
for surgery, scheduled surgical procedure, anesthesia modality, and scheduled surgery
length), demographics (including gender, age, and race), allergies, history of smoking,
history of alcohol or drug abuse, medications, history of postoperative nausea and vomiting
(PONV), and history of motion sickness. A physical examination will also be performed at this
time.
Day 0
Upon enrolment, subjects will be randomly assigned in a 1:1 ratio, from a pre-determined
randomization schedule, by the research pharmacist to one of two anesthetic treatment groups:
Anesthesia maintained under desflurane or anesthesia maintained under sevoflurane.
Prior to surgery, a urine or serum pregnancy test will be performed and vitals will be
collected. Subjects' baseline pain and nausea will be assessed using an eleven point numeric
rating scale (NRS-11)15, where 0 is equivalent to none and 10 is equivalent to severe, prior
to entering the operating room (OR).
Cognitive function will be evaluated in terms of level of orientation, memory, and
concentration (SOMCT). The SOMCT evaluation is performed by requesting the subjects' to
recall the current year and month, one sentence, and to repeat in both numerical and reverse
order the sequence of the months through the year. These 6 variables yield scores ranging
from 0 to 28, with higher scores indicating better cognitive function (Appendix 2).
Subjects will be premedicated with 0.5 to 2 mg midazolam IV in the pre-operative holding
area. The subject will be transported to the operating room and assisted onto the operating
table, and ASA standard monitoring will be applied as determined by the anesthesiologist and
must include an oxygen saturation monitor and bispectral index (BIS) monitor. The BIS monitor
will be applied prior to the induction of anesthesia. Subject vital signs and BIS values will
be recorded every 5 minutes throughout the operation and recorded on the anesthesia record.
The subject will be preoxygenated using spontaneous mask ventilation at 100% fraction of
inspired oxygen inspired oxygen fraction (FiO2) and a fresh gas flow of 6 L/min of oxygen for
one to four minutes prior to induction. Anesthesia induction will be performed via bolus
injection of 2 mg/kg IV propofol and 1 to 2 mcg/kg of fentanyl intravenous (IV) bolus. After
completion of bolus injection of propofol, the inhaled anesthetic vaporizer will be opened to
1 MAC (5.4 to 7.4% for desflurane and 1.4 to 2.5% for sevoflurane) based on study
randomization for one to two minutes using masked ventilation. Following the masked
ventilation a jaw thrust maneuver will be performed, the fresh gas inflow (not vaporizer)
will be turned off, and a lubricated LMA will be inserted. The size and brand of of LMA will
be recorded. After verification of proper placement and a seal around the LMA, the inflow
will be immediately turned back to 4 to 6 L/min of 100% oxygen with the vaporizer set at 1
MAC for three minutes and the patient will be placed on volume or pressure control mechanical
ventilation. Ventilation will be verified via documentation of bilateral breath sounds and
chest rise. Following three to five minutes, the inhalational anesthesia will be maintained
with either desflurane or sevoflurane (0.5 to 1 MAC) inspired in a 50:50 air/oxygen mixture
at a total gas flow rate of 1 L/min. This will be based on the randomization of the subject
prior to surgery to one of the two groups of inhaled anesthetics. Additional boluses of
fentanyl, propofol, or vasopressors will be administered as needed to maintain analgesia and
hemodynamics, including heart rate, spontaneous respiratory rate, and mean arterial pressure
(MAP), within 20% of baseline. At end of procedure, upon closure of surgical incision,
inhalational anesthetic agents will be discontinued and fresh gas flow will be increased to 6
to 8 L/min of 100% oxygen. All patients will be maintained with inhaled anesthestic that will
not be below 0.5 MAC for either desflurane or sevoflurane throughout the surgery.
Each episode of coughing during induction of anesthesia until the subject is awake and
oriented will be recorded by a blinded observer and graded according to the scale below
Coughing is defined as; 1 if a single cough occurred and oxygen saturation (SpO2) ≥ 95 %; 2
if multiple coughs occurred and SpO2 ≥ 95 %; 3 if multiple coughs occurred and SpO2 < 95 %; 4
if multiple coughs occurred, SpO2 < 95 % and coughing requires administration of an IV
medication.
Awakening from anesthesia (eye-opening) will be assessed by the research staff by asking the
subjects to follow verbal commands only (no touch) at one-minute intervals after the
discontinuation of volatile anesthetics. The time to appropriateness for extubation will also
be recorded in one-minute intervals after discontinuation of the inhalational agent. Prior to
removal of the LMA, the subject will be determined to be awake by "eyes-open" to command and
deemed appropriate by the anesthesiologist.
Anesthesia and procedure start and end time, admission and discharge time to the
post-anesthesia care unit (PACU) and time to discharge from the hospital will also be
recorded.
Post-anesthesia recovery (physical status) will be evaluated, according to the Aldrete
score16, 5 minutes after extubation and every 5 minutes until the subject reaches an Aldrete
score ≥ 9. Subjects should be able to move the extremities spontaneously or on command, to
breathe and cough, have systolic blood pressure values within 20 mmHg of the pre-anesthetic
levels or baseline levels, alert or arousable to quiet voice, and able to maintain SpO2 > 90
% with supplementary O2 administration through a face mask at the lowest concentration needed
to ensure Pao2 between 100 and 200 mmHg (Appendix 1) After subjects have reached a
postoperative Aldrete score ≥9, the research staff will perform a SOMCT test to evaluate
postoperative cognitive function every 15 minutes for the first hour after surgery and at the
time of discharge from the PACU.
At 24 hours after surgery overall satisfaction will be assessed by asking the subjects about
their experience with the anesthetic medication using a 3 point rating scale, by personal
interview or phone call, by a blinded research staff. Satisfaction will be rated on a scale:
2 being equivalent to highly satisfied, 1 being equivalent to satisfied and 0 being
equivalent to dissatisfied.
All medications taken in the 24 hours prior to treatment will be recorded. Any drug with
potential antiemetic properties, intraoperative medication, and daily consumption of opioids
will be recorded for 24 hours postoperatively or until discharge from the hospital or
whichever comes first. Adverse events and serious adverse events will be recorded from time
of consent until discharge.
Safety Assessments:
Safety parameters will be assessed by monitoring vital signs, adverse events, and either
urine or serum pregnancy test. A physical exam will be performed at screening.
The occurrence of adverse events (AE) and serious adverse events (SAE) will be recorded from
time to consent until discharge. For each adverse event, the relationship to the study
medication, severity, expectedness of an adverse event and outcome will be determined by the
principal investigator and recorded in the study source accordingly.
In the case a subject withdraws from the study because of a serious adverse event (SAE), the
local Institutional Review Board (IRB) will be notified within 10 days.
Adverse event definition
An AE is defined as any untoward medical occurrence in a patient or clinical investigation
subject who has been administered a medicinal product and which does not necessarily have to
have a causal relationship with this treatment. An AE can be any unfavorable and unintended
sign, symptom, abnormal laboratory finding, or a temporal disease associated with the use of
a study drug, whether or not considered related to the study drug.
Planned hospital admissions and/or surgical operations for an illness or disease that existed
before the subject was enrolled in a clinical study are considered part of the subjects'
medical history and are not to be considered AEs.
Serious adverse event
A SAE is any untoward medical occurrence that at any dose:
- Results in death
- Is life-threatening
- Results in persistent or significant disability/incapacity
- Requires in-subject hospitalization or prolongs hospitalization
- Is a congenital anomaly/birth defect
- Is another medically-significant event that, based upon appropriate medical judgment,
may jeopardize the subject and may require medical or surgical intervention to prevent
one of the outcomes listed above
Withdrawal criteria from the study
According with the Declaration of Helsinki, participants have the right to withdraw from the
study at any time for any reason. The principal investigator also has the right to remove a
subject from the study. Reasons for which a subject may be removed from the study include:
- An adverse event
- The request of the subject, his/her legal representative or caregiver, investigator,
whether for administrative or any other reasons
- Non - compliance with medication, protocol violation or unreliable, behavior
- Any clinically significant abnormal laboratory values or other clinically significant
abnormalities identified by the principal investigator according to his clinical
judgment. These will be followed by appropriate tests and/or procedures until these
values have returned to normal, to clinically acceptable levels, or can be attributed to
other causes other than study drug
The principal investigator may withdraw an enrolled and treated subject from the study for
any of the following reasons:
- Occurrence of a serious or intolerable adverse event
- Emergence of a clinically significant change in a laboratory parameter(s)
- The subject requests to be discontinued from the study
- A protocol violation sufficiently serious as to require subject withdrawal
- General or specific changes in the subject's condition that render further treatment
unreasonable or unsafe within the standards of clinical practice in the judgment of the
principal investigator or treating physician.
Any subject may leave the study at any time. If the subject decides to stop participating in
the study, there will be no penalty. The subjects will not lose any benefits to which they
are otherwise entitled.
