Trial Outcomes & Findings for Safety and Efficacy of Oral Midazolam for Perioperative Anxiety Relief of Patients Undergoing Mohs Micrographic Surgery (NCT NCT00578214)

Results Overview

A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety).

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

75 participants

Primary outcome timeframe

Baseline (prior to drug administration)

Results posted on

2012-02-09

Participant Flow

Patients undergoing outpatient Mohs surgery at the Mayo Clinic in Rochester, MN were included in either the randomized arms (midazolam vs placebo) or in the prospective midazolam arm. The study was performed between March 2007 and June 2008.

Participant milestones

Participant milestones
Measure	Randomized Midazolam Randomized patients receiving single-dose midazolam syrup	Placebo Randomized patients receiving placebo syrup	Prospective Midazolam Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Overall Study STARTED	22	22	31
Overall Study COMPLETED	22	22	31
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Oral Midazolam for Perioperative Anxiety Relief of Patients Undergoing Mohs Micrographic Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Midazolam n=22 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible	Total n=75 Participants Total of all reporting groups
Age Continuous	71.9 years STANDARD_DEVIATION 11.5 • n=5 Participants	70.1 years STANDARD_DEVIATION 12.8 • n=7 Participants	62.9 years STANDARD_DEVIATION 14.1 • n=5 Participants	67.7 years STANDARD_DEVIATION 13.4 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants	40 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	12 Participants n=7 Participants	10 Participants n=5 Participants	35 Participants n=4 Participants
Region of Enrollment United States	22 participants n=5 Participants	22 participants n=7 Participants	31 participants n=5 Participants	75 participants n=4 Participants
Weight at study entry	83.1 kg STANDARD_DEVIATION 13.23 • n=5 Participants	80.6 kg STANDARD_DEVIATION 11.82 • n=7 Participants	87.8 kg STANDARD_DEVIATION 20.16 • n=5 Participants	84.3 kg STANDARD_DEVIATION 16.2 • n=4 Participants
Prior Mohs Micrographic Surgery No	16 participants n=5 Participants	17 participants n=7 Participants	21 participants n=5 Participants	54 participants n=4 Participants
Prior Mohs Micrographic Surgery Yes	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants	18 participants n=4 Participants
Prior Mohs Micrographic Surgery Unknown	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Type of Non-melanoma Skin Cancer Basal Cell Carcinoma	13 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants	46 participants n=4 Participants
Type of Non-melanoma Skin Cancer Squamous Cell Carcinoma	9 participants n=5 Participants	10 participants n=7 Participants	8 participants n=5 Participants	27 participants n=4 Participants
Type of Non-melanoma Skin Cancer Basal Cell and Squamous Cell Carcinomas	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (prior to drug administration)

Population: The analysis was done on the patients who completed the assessment. One patient in the randomized midazolam arm, 2 patients in the placebo arm, and 1 patient in the prospective midazolam arm did not complete this assessment.

A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=21 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=30 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Anxiety at Baseline	1.3 units on a scale Standard Deviation 1.5	1.4 units on a scale Standard Deviation 1.6	3.4 units on a scale Standard Deviation 2.7

PRIMARY outcome

Timeframe: 60 and 120 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. One patient in the randomized midazolam arm did not complete this assessment.

A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=21 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Anxiety at 60 and 120 Minutes 60 min patient anxiety	0.1 units on a scale Standard Deviation 0.5	0.8 units on a scale Standard Deviation 0.9	1.0 units on a scale Standard Deviation 1.7
Patient Anxiety at 60 and 120 Minutes 120 min patient anxiety	0.2 units on a scale Standard Deviation 0.5	0.4 units on a scale Standard Deviation 0.8	0.8 units on a scale Standard Deviation 1.6

SECONDARY outcome

Timeframe: Baseline (prior to drug administration)

Population: The analysis was done on the patients who completed the assessment. One patient in the randomized midazolam arm did not complete this assessment.

A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=21 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Alertness at Baseline	0.2 units on a scale Standard Deviation 0.6	0.2 units on a scale Standard Deviation 0.7	0.2 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: 60 and 120 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. One patient in the randomized midazolam arm and 1 patient in the prospective midazolam arm did not complete this assessment.

A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=21 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=30 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Alertness at 60 and 120 Minutes 60 min patient alertness	3.7 units on a scale Standard Error 4.0	0.7 units on a scale Standard Error 1.6	5.1 units on a scale Standard Error 3.4
Patient Alertness at 60 and 120 Minutes 120 min patient alertness	2.1 units on a scale Standard Error 2.9	0.5 units on a scale Standard Error 1.1	3.4 units on a scale Standard Error 2.9

SECONDARY outcome

Timeframe: baseline (prior to drug administration) and 60 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. One patient in the prospective midazolam arm did not complete this assessment.

Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=22 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=30 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Cognitive Function at Baseline and 60 Minutes Baseline Cognitive Function	28.9 units on a scale Standard Deviation 1.4	29.3 units on a scale Standard Deviation 0.9	29.2 units on a scale Standard Deviation 1.9
Patient Cognitive Function at Baseline and 60 Minutes 60 min Cognitive Function	22.9 units on a scale Standard Deviation 10.6	29.4 units on a scale Standard Deviation 0.7	24.3 units on a scale Standard Deviation 10.9

SECONDARY outcome

Timeframe: 120 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Two patients in the placebo arm did not complete this assessment.

Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function).

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=22 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Patient Cognitive Function at 120 Minutes	26.0 units on a scale Standard Deviation 8.6	29.2 units on a scale Standard Deviation 1.2	27.5 units on a scale Standard Deviation 7.0

SECONDARY outcome

Timeframe: 30 minutes after drug administration

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=22 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=22 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Blood Pressure at 30 Minutes 30 min Systolic Blood Pressure	121.4 mm Hg Standard Deviation 19.50	125.9 mm Hg Standard Deviation 12.24	118.5 mm Hg Standard Deviation 16.99
Blood Pressure at 30 Minutes 30 min Diastolic Blood Pressure	67.1 mm Hg Standard Deviation 12.9	68.4 mm Hg Standard Deviation 7.82	63.2 mm Hg Standard Deviation 10.58

SECONDARY outcome

Timeframe: 30 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. One patient in the placebo arm did not complete this assessment.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=22 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=21 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Heart Rate at 30 Minutes	61.7 heart beats per minute Standard Deviation 14.84	64.3 heart beats per minute Standard Deviation 8.16	72.1 heart beats per minute Standard Deviation 12.65

SECONDARY outcome

Timeframe: 30 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 2 patients in the placebo arm did not complete this assessment.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Respiratory Rate at 30 Minutes	19.4 breaths per minute Standard Deviation 12.26	16.1 breaths per minute Standard Deviation 2.63	16.2 breaths per minute Standard Deviation 3.07

SECONDARY outcome

Timeframe: 30 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 2 patients in the placebo arm did not complete this assessment.

Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Pulse Oximetry at 30 Minutes	94.5 percentage of oxygenation Standard Deviation 2.18	95.6 percentage of oxygenation Standard Deviation 2.11	95.6 percentage of oxygenation Standard Deviation 2.56

SECONDARY outcome

Timeframe: 60 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 2 patients in the placebo arm did not complete this assessment.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Blood Pressure at 60 Minutes 60 min systolic blood pressure	120.1 mm Hg Standard Deviation 18.10	131.9 mm Hg Standard Deviation 14.59	113.5 mm Hg Standard Deviation 15.61
Blood Pressure at 60 Minutes 60 min diastolic blood pressure	65.3 mm Hg Standard Deviation 9.17	69.5 mm Hg Standard Deviation 8.69	61.5 mm Hg Standard Deviation 10.04

SECONDARY outcome

Timeframe: 60 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 2 patients in the placebo arm did not complete this assessment.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=20 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Heart Rate at 60 Minutes	60.3 heart beats per minute Standard Deviation 13.94	61.4 heart beats per minute Standard Deviation 7.45	69.6 heart beats per minute Standard Deviation 10.75

SECONDARY outcome

Timeframe: 60 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 3 patients in the placebo arm did not complete this assessment.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=19 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Respiratory Rate at 60 Minutes	20.6 breaths per minute Standard Deviation 12.33	16.3 breaths per minute Standard Deviation 2.43	16.8 breaths per minute Standard Deviation 2.69

SECONDARY outcome

Timeframe: 60 minutes after drug administration

Population: The analysis was done on the patients who completed the assessment. Three patients in the randomized midazolam arm and 3 patients in the placebo arm did not complete this assessment.

Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%.

Outcome measures

Outcome measures
Measure	Randomized Midazolam n=19 Participants Randomized patients receiving single-dose midazolam syrup	Placebo n=19 Participants Randomized patients receiving placebo syrup	Prospective Midazolam n=31 Participants Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Pulse Oximetry at 60 Minutes	94.5 percentage of oxygenation Standard Deviation 2.43	96.4 percentage of oxygenation Standard Deviation 1.81	95.5 percentage of oxygenation Standard Deviation 3.03

Adverse Events

Randomized Midazolam

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Prospective Midazolam

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Randomized Midazolam n=22 participants at risk Randomized patients receiving single-dose midazolam syrup	Placebo n=22 participants at risk Randomized patients receiving placebo syrup	Prospective Midazolam n=31 participants at risk Open-label, dose of Midazolam based on patient's weight, additional doses to control anxiety were possible
Respiratory, thoracic and mediastinal disorders Mild and transient hypoxia	0.00% 0/22 • Patients were assessed for adverse events (AEs) during the 120 minutes after drug administration. Patients also were contacted by phone within 24 hours of the procedure using a specific inventory questionnaire to determine if there were any delayed AEs.	0.00% 0/22 • Patients were assessed for adverse events (AEs) during the 120 minutes after drug administration. Patients also were contacted by phone within 24 hours of the procedure using a specific inventory questionnaire to determine if there were any delayed AEs.	3.2% 1/31 • Number of events 1 • Patients were assessed for adverse events (AEs) during the 120 minutes after drug administration. Patients also were contacted by phone within 24 hours of the procedure using a specific inventory questionnaire to determine if there were any delayed AEs.

Additional Information

Dr. Clark C. Otley

Mayo Clinic

Phone: 507-284-3579

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place