PedsPreMed: A Comparison of Midazolam and Zolpidem as Oral Premedication in Children

• Sponsor: Loma Linda University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02096900
• Collaborator: (none)
• Enrollment: 86
• Location: 1
• Arms: 2
• Actual Duration (Months): 21.5
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

The purpose of this investigator-initiated study is to compare the efficacy of oral midazolam and zolpidem for preoperative sedation, anxiety of patient, and caregiver anxiety at the time of separation, and ease of mask acceptance at induction in children. Subjects will be randomized to receive oral medication midazolam or zolpidem approximately 30 minutes prior to surgery. No placebo will be administered in this study. Subjects will be male and female children between 2 and 9 years of age. In total, subject participation will last approximately the duration of their preoperative, perioperative, and immediate postoperative period. A member of the research team will recruit subjects preoperatively in the operating room holding area prior to surgery. Consent will take place at the time of recruitment in the preoperative holding area following a detailed explanation of the study and medications involved in the study. Participants will be of ASA (American Society of Anesthesiologists) class I-II, undergoing surgical procedures of at least 2 hours duration, and expected to remain inpatient for at least 23 hours postoperatively.

Condition or Disease	Intervention/Treatment	Phase
Parental/Caregiver Anxiety; Child's Anxiety	Drug: zolpidem; Drug: Midazolam	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Comparison of Midazolam and Zolpidem as Oral Premedication in Children
• Actual Study Start Date: Jul 21, 2014
• Actual Primary Completion Date: May 6, 2016
• Actual Study Completion Date: May 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: zolpidem zolpidem given orally 0.25mg/kg pre-operatively single dose	Drug: zolpidem; Zolpidem will be given one time at 0.25 mg/kg pre-operatively; Other Names: ambien
Active Comparator: midazolam midazolam will be given at 0.5mg/kg, pre-operatively single dose	Drug: Midazolam; Other Names: versed

Outcome Measures

Primary Outcome Measures

1. Patient Anxiety at the Time of Separation [Up to 24 hours including preoperative, preoperative, and postoperative periods.]

   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.

Secondary Outcome Measures

1. Mask Acceptance Score [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.

2. Presence of Emergence Delirium During Recovery [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.

3. Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI) [Preoperative holding area from the time of informed consent until caregiver/patient separation.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 9 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Pediatric patients ages 2-9 years

• ASA class I-II

• inpatient surgeries of at least 2 hours duration

• requiring postoperative admission of at least 23 hours Exclusion Criteria:

Exclusion Criteria:

• contraindication to preoperative sedation, known allergy or sensitivity to the study medications,

• those who lack legal representative consent

• Patients with weights lying below the 5th percentile or above the 95th percentile according to the current published CDC growth chart will also be excluded regardless of existing specific contraindication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University	Loma Linda	California	United States	92354

Sponsors and Collaborators

• Loma Linda University

Investigators

• Principal Investigator: Amgad Hanna, MD, Loma Linda University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Davinder Ramsingh, MD, Principal Investigator, Loma Linda University
• ClinicalTrials.gov Identifier: NCT02096900
• Other Study ID Numbers: 5140032
• First Posted: Mar 26, 2014
• Last Update Posted: Mar 14, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Davinder Ramsingh, MD, Principal Investigator, Loma Linda University: Pre-medication; Pre-operative anxiety
• Additional relevant MeSH terms: Anxiety Disorders; Midazolam; Zolpidem

Study Results

Participant Flow

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Period Title: Overall Study
STARTED	42	44
COMPLETED	38	42
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Midazolam	Zolpidem	Total
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose	Total of all reporting groups
Overall Participants	38	42	80
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.34 (2.21)	6.07 (2.34)	6.20 (2.27)
Sex: Female, Male (Count of Participants)
Female	21 55.3%	19 45.2%	40 50%
Male	17 44.7%	23 54.8%	40 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 57.9%	25 59.5%	47 58.8%
Not Hispanic or Latino	16 42.1%	17 40.5%	33 41.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.6%	0 0%	1 1.3%
Native Hawaiian or Other Pacific Islander	1 2.6%	0 0%	1 1.3%
Black or African American	0 0%	2 4.8%	2 2.5%
White	36 94.7%	40 95.2%	76 95%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	38 100%	42 100%	80 100%
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	23.16 (6.20)	23.18 (7.21)	23.17 (6.71)
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	117.32 (14.55)	115.34 (15.92)	116.29 (15.23)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	16.73 (1.92)	17.60 (4.02)	17.19 (3.21)
ASA physical status (Count of Participants)
ASA PS I	12 31.6%	14 33.3%	26 32.5%
AS PS II	26 68.4%	28 66.7%	54 67.5%
Time from drug administration to parental separation (minutes) (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	31.53 (12.20)	34.98 (16.00)	33.13 (14.31)
Duration of anesthesia (minutes) (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	185.58 (72.20)	205.79 (97.60)	196.46 (86.86)

Outcome Measures

1. Primary Outcome

Title	Patient Anxiety at the Time of Separation
Description	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.
Time Frame	Up to 24 hours including preoperative, preoperative, and postoperative periods.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Measure Participants	38	42
Median (Inter-Quartile Range) [units on a scale]	26.69	30.00

2. Secondary Outcome

Title	Mask Acceptance Score
Description	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.
Time Frame	During induction of general anesthesia.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Measure Participants	38	42
Mask acceptance score 1-2	34 89.5%	29 69%
Mask acceptance score 3-4	4 10.5%	13 31%

3. Secondary Outcome

Title	Presence of Emergence Delirium During Recovery
Description	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.
Time Frame	Up to 30 minutes after child's first eye opening in the post-operative period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Measure Participants	38	42
No	26 68.4%	32 76.2%
Yes	12 31.6%	10 23.8%

4. Secondary Outcome

Title	Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI)
Description	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.
Time Frame	Preoperative holding area from the time of informed consent until caregiver/patient separation.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Measure Participants	24	27
STAIY-1 (at informed consent)	41.74 (10.66)	41.12 (10.88)
STAIY-2 (at informed consent)	31.81 (8.29)	34.12 (8.29)
STAIY-1 (at separation)	44.33 (9.58)	43.85 (13.70)

5. Post-Hoc Outcome

Title	Modified Yale Preoperative Anxiety Scale (mYPAS) Score at Separation (mYPAS2) Based on Baseline (mYPAS1) Score.
Description	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.
Time Frame	Up to 24 hours including pre-operative, peri-operative and post-operative periods.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Midazolam	Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose	zolpidem was given orally 0.25mg/kg pre-operatively single dose
Measure Participants	38	42
mYPAS2 - non-anxious baseline	23.32	28.30
mYPAS2 - anxious baseline	29.97	60.75

Adverse Events

Time Frame	Adverse event data were collected during the study participation time which was about one day for each subject.
Arm/Group Title	Midazolam		Zolpidem
Arm/Group Description	midazolam was given at 0.5mg/kg, pre-operatively single dose		zolpidem was given orally 0.25mg/kg pre-operatively single dose
All Cause Mortality
	Midazolam		Zolpidem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/42 (0%)
Serious Adverse Events
	Midazolam		Zolpidem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/42 (0%)
Other (Not Including Serious) Adverse Events
	Midazolam		Zolpidem
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)		5/42 (11.9%)
Gastrointestinal disorders
Epigastric pain	0/38 (0%)	0	1/42 (2.4%)	1
Nervous system disorders
Double vision	0/38 (0%)	0	2/42 (4.8%)	2
Visual Hallucinations	0/38 (0%)	0	2/42 (4.8%)	2
Involuntary tongue movements	0/38 (0%)	0	1/42 (2.4%)	1
Dysphoria	0/38 (0%)	0	1/42 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Oxygen desatruation	1/38 (2.6%)	1	0/42 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.