Trial Outcomes & Findings for A Comparison of Midazolam and Zolpidem as Oral Premedication in Children (NCT NCT02096900)

NCT ID: NCT02096900

Last Updated: 2019-03-14

Results Overview

The primary outcome measure of patient anxiety will be measured using the validated Modified Yale Preoperative Anxiety Score (mYPAS). The mYPAS is the current standard for evaluation of anxiety in children receiving anesthesia for surgical procedures. The modified Yale Preoperative Anxiety scale (m-YPAS) is a structured observational measure of preoperative anxiety in children. It was developed by the study group lead by Kain Z. It consists of assessment of 27 items in 5 domains of behavior indicating anxiety in young children; activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each item is weighted in calculation of the total score that ranges from 22.5 -100. Children with a score above 30 are considered anxious while those with the score of 30 or less were considered not anxious.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

86 participants

Primary outcome timeframe

Up to 24 hours including preoperative, preoperative, and postoperative periods.

Results posted on

2019-03-14

Participant Flow

Participant milestones

Participant milestones
Measure	Midazolam midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem zolpidem was given orally 0.25mg/kg pre-operatively single dose
Overall Study STARTED	42	44
Overall Study COMPLETED	38	42
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Midazolam midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem zolpidem was given orally 0.25mg/kg pre-operatively single dose
Overall Study Did not receive medication	3	1
Overall Study Surgery cancelled- medication received	1	1

Baseline Characteristics

A Comparison of Midazolam and Zolpidem as Oral Premedication in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Midazolam n=38 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose	Total n=80 Participants Total of all reporting groups
Age, Continuous	6.34 years STANDARD_DEVIATION 2.21 • n=5 Participants	6.07 years STANDARD_DEVIATION 2.34 • n=7 Participants	6.20 years STANDARD_DEVIATION 2.27 • n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	23 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	25 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	40 Participants n=7 Participants	76 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	38 Participants n=5 Participants	42 Participants n=7 Participants	80 Participants n=5 Participants
Weight (kg)	23.16 kg STANDARD_DEVIATION 6.20 • n=5 Participants	23.18 kg STANDARD_DEVIATION 7.21 • n=7 Participants	23.17 kg STANDARD_DEVIATION 6.71 • n=5 Participants
Height (cm)	117.32 cm STANDARD_DEVIATION 14.55 • n=5 Participants	115.34 cm STANDARD_DEVIATION 15.92 • n=7 Participants	116.29 cm STANDARD_DEVIATION 15.23 • n=5 Participants
BMI	16.73 kg/m^2 STANDARD_DEVIATION 1.92 • n=5 Participants	17.60 kg/m^2 STANDARD_DEVIATION 4.02 • n=7 Participants	17.19 kg/m^2 STANDARD_DEVIATION 3.21 • n=5 Participants
ASA physical status ASA PS I	12 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants
ASA physical status AS PS II	26 Participants n=5 Participants	28 Participants n=7 Participants	54 Participants n=5 Participants
Time from drug administration to parental separation (minutes)	31.53 minutes STANDARD_DEVIATION 12.20 • n=5 Participants	34.98 minutes STANDARD_DEVIATION 16.00 • n=7 Participants	33.13 minutes STANDARD_DEVIATION 14.31 • n=5 Participants
Duration of anesthesia (minutes)	185.58 minutes STANDARD_DEVIATION 72.20 • n=5 Participants	205.79 minutes STANDARD_DEVIATION 97.60 • n=7 Participants	196.46 minutes STANDARD_DEVIATION 86.86 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 hours including preoperative, preoperative, and postoperative periods.

Outcome measures

Outcome measures
Measure	Midazolam n=38 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose
Patient Anxiety at the Time of Separation	26.69 units on a scale Interval 23.3 to 36.6	30.00 units on a scale Interval 23.3 to 38.2

SECONDARY outcome

Timeframe: During induction of general anesthesia.

Mask acceptance by the patient, will be measured on a 4-point scale adapted from a similar trial. Score of 1 and 2 indicates satisfactory mask acceptance. Score of 3 or 4 indicates unsatisfactory mask acceptance during induction of general anesthesia.

Outcome measures

Outcome measures
Measure	Midazolam n=38 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose
Mask Acceptance Score Mask acceptance score 1-2	34 Participants	29 Participants
Mask Acceptance Score Mask acceptance score 3-4	4 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to 30 minutes after child's first eye opening in the post-operative period.

Presence or absence of emergence delirium during recovery, will be assessed using the pediatric anesthesia emergence delirium (PAED) scale recorded at 5-minute intervals for 20 minutes following the child's spontaneous eye opening. PAED score of ≥12 at any time indicates presence of emergence delirium.

Outcome measures

Outcome measures
Measure	Midazolam n=38 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose
Presence of Emergence Delirium During Recovery No	26 Participants	32 Participants
Presence of Emergence Delirium During Recovery Yes	12 Participants	10 Participants

SECONDARY outcome

Timeframe: Preoperative holding area from the time of informed consent until caregiver/patient separation.

Population: only total of 51 subjects were analyzed. Caregivers of 29 subjects were given incorrect form to fill at time of separation rendering data not applicable for analysis for the 29 subjects.

Parental/caregiver anxiety, was assessed using the validated State-Trait Anxiety Inventory for Adults (STAI), a validated self-evaluation questionnaire. The STAI is compromised of separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale (STAI Form Y-1) consists of twenty statements that evaluate how respondents feel "right now, at this moment". The T-Anxiety scale (STAI Form Y-2) consists of twenty statements that assess how respondents generally feel. The score ranges from 20 (most relaxed) to 80 (highest stress). The baseline STAI inventory was completed by e parent/caregiver after obtaining the informed consent in the preoperative holding area and before the subject was separated from the caregiver. Baseline STAI inventory consisted of form STAIY-1 (State Anxiety) and form STAIY-2 (Trait Anxiety) anxiety. After caregiver/patient separation,form STAIY-1(State Anxiety) was completed again by the caregiver.

Outcome measures

Outcome measures
Measure	Midazolam n=24 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=27 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose
Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI) STAIY-1 (at informed consent)	41.74 units on a scale Standard Deviation 10.66	41.12 units on a scale Standard Deviation 10.88
Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI) STAIY-2 (at informed consent)	31.81 units on a scale Standard Deviation 8.29	34.12 units on a scale Standard Deviation 8.29
Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI) STAIY-1 (at separation)	44.33 units on a scale Standard Deviation 9.58	43.85 units on a scale Standard Deviation 13.70

POST_HOC outcome

Timeframe: Up to 24 hours including pre-operative, peri-operative and post-operative periods.

Midazolam group participants will be separated into two groups; non-anxious (mYPAS1 ≤ 30) at baseline and anxious (mYPAS1 \> 30) at baseline. The mYAPS2 scores of these two groups will be compared to the mYPAS2 scores of the Zolpidem group participants. The modified Yale Preoperative Anxiety scale (m-YPAS) is a structured observational measure of preoperative anxiety in children that takes less than a minute to preform. It consists of assessment of 27 items in 5 domains of behavior indicating anxiety in young children; activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each item is weighted in calculation of the total score that ranges from 22.5 -100. A cut off 30 on the m-YPAS scale was found to balance the high specificity and sensitivity while maintaining high positive predictive value. Children with a score above 30 are considered anxious while those with the score of 30 or less were considered not anxious.

Outcome measures

Outcome measures
Measure	Midazolam n=38 Participants midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 Participants zolpidem was given orally 0.25mg/kg pre-operatively single dose
Modified Yale Preoperative Anxiety Scale (mYPAS) Score at Separation (mYPAS2) Based on Baseline (mYPAS1) Score. mYPAS2 - non-anxious baseline	23.32 units on a scale Interval 23.3 to 30.8	28.30 units on a scale Interval 23.3 to 42.5
Modified Yale Preoperative Anxiety Scale (mYPAS) Score at Separation (mYPAS2) Based on Baseline (mYPAS1) Score. mYPAS2 - anxious baseline	29.97 units on a scale Interval 23.3 to 46.6	60.75 units on a scale Interval 36.6 to 96.7

Adverse Events

Midazolam

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Zolpidem

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Midazolam n=38 participants at risk midazolam was given at 0.5mg/kg, pre-operatively single dose	Zolpidem n=42 participants at risk zolpidem was given orally 0.25mg/kg pre-operatively single dose
Respiratory, thoracic and mediastinal disorders Oxygen desatruation	2.6% 1/38 • Number of events 1 • Adverse event data were collected during the study participation time which was about one day for each subject.	0.00% 0/42 • Adverse event data were collected during the study participation time which was about one day for each subject.
Nervous system disorders Double vision	0.00% 0/38 • Adverse event data were collected during the study participation time which was about one day for each subject.	4.8% 2/42 • Number of events 2 • Adverse event data were collected during the study participation time which was about one day for each subject.
Gastrointestinal disorders Epigastric pain	0.00% 0/38 • Adverse event data were collected during the study participation time which was about one day for each subject.	2.4% 1/42 • Number of events 1 • Adverse event data were collected during the study participation time which was about one day for each subject.
Nervous system disorders Visual Hallucinations	0.00% 0/38 • Adverse event data were collected during the study participation time which was about one day for each subject.	4.8% 2/42 • Number of events 2 • Adverse event data were collected during the study participation time which was about one day for each subject.
Nervous system disorders Involuntary tongue movements	0.00% 0/38 • Adverse event data were collected during the study participation time which was about one day for each subject.	2.4% 1/42 • Number of events 1 • Adverse event data were collected during the study participation time which was about one day for each subject.
Nervous system disorders Dysphoria	0.00% 0/38 • Adverse event data were collected during the study participation time which was about one day for each subject.	2.4% 1/42 • Number of events 1 • Adverse event data were collected during the study participation time which was about one day for each subject.

Additional Information

Amgad H. Hanna, MD

Loma Linda University

Phone: 909-558-4475

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place