Trial Outcomes & Findings for Evaluation of Oral Midazolam in First-trimester Surgical Abortions (NCT NCT01830881)

NCT ID: NCT01830881

Last Updated: 2018-06-25

Results Overview

Subjects will be asked to rate anxiety and pain at the time of uterine aspiration by marking along a 100 mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 124 participants
• Primary outcome timeframe: at time of uterine aspiration (30-60 minutes after premedication)
• Results posted on: 2018-06-25

Participant Flow

This randomized, double-blind, placebo-controlled trial was conducted at Planned Parenthood Columbia/ Willamette in Portland, Oregon, between May 2013 and December 2013.

Participant milestones

Measure	Midazolam and Ibuprofen 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Placebo-cherry Syrup and Ibuprofen 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Overall Study STARTED	62	62
Overall Study COMPLETED	62	61
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Measure	Midazolam and Ibuprofen 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Placebo-cherry Syrup and Ibuprofen 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Overall Study Changed decision to have an abortion	0	1

Baseline Characteristics

Evaluation of Oral Midazolam in First-trimester Surgical Abortions

Baseline characteristics by cohort

Measure	Placebo-cherry Syrup and Ibuprofen n=62 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Total n=124 Participants Total of all reporting groups
Age, Continuous	25.8 years STANDARD_DEVIATION 5.3 • n=5 Participants	25.5 years STANDARD_DEVIATION 5.8 • n=7 Participants	25.6 years STANDARD_DEVIATION 5.5 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	62 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=5 Participants	54 Participants n=7 Participants	107 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	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	42 Participants n=7 Participants	86 Participants n=5 Participants
Race (NIH/OMB) More than one race	11 Participants n=5 Participants	13 Participants n=7 Participants	24 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
Parity Nulliparous	38 participants n=5 Participants	32 participants n=7 Participants	70 participants n=5 Participants
Parity Parous	24 participants n=5 Participants	30 participants n=7 Participants	54 participants n=5 Participants
Previous vaginal deliveries Yes	20 participants n=5 Participants	22 participants n=7 Participants	42 participants n=5 Participants
Previous vaginal deliveries No	42 participants n=5 Participants	40 participants n=7 Participants	82 participants n=5 Participants
Previous surgical abortion Yes	21 participants n=5 Participants	23 participants n=7 Participants	44 participants n=5 Participants
Previous surgical abortion No	41 participants n=5 Participants	39 participants n=7 Participants	80 participants n=5 Participants
Level of menstrual symptoms Easy or mild cramping	30 participants n=5 Participants	40 participants n=7 Participants	70 participants n=5 Participants
Level of menstrual symptoms Requiring medication or unable to attend work	32 participants n=5 Participants	22 participants n=7 Participants	54 participants n=5 Participants
BMI	25.9 kg/m2 STANDARD_DEVIATION 6.0 • n=5 Participants	25.9 kg/m2 STANDARD_DEVIATION 5.5 • n=7 Participants	25.9 kg/m2 STANDARD_DEVIATION 5.7 • n=5 Participants
Self-reported depression Yes	19 participants n=5 Participants	14 participants n=7 Participants	33 participants n=5 Participants
Self-reported depression No	43 participants n=5 Participants	48 participants n=7 Participants	91 participants n=5 Participants
Self-reported anxiety Yes	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants
Self-reported anxiety No	48 participants n=5 Participants	48 participants n=7 Participants	96 participants n=5 Participants

PRIMARY outcome

Timeframe: at time of uterine aspiration (30-60 minutes after premedication)

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subjects will be asked to rate anxiety and pain at the time of uterine aspiration by marking along a 100 mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Perception of Pain and Anxiety During Uterine Aspiration Pain with Aspiration	74.3 mm Standard Deviation 20.6	70.1 mm Standard Deviation 22.1
Subject Perception of Pain and Anxiety During Uterine Aspiration Anxiety with Aspiration	68.2 mm Standard Deviation 28.1	60.9 mm Standard Deviation 27.3

SECONDARY outcome

Timeframe: Baseline (upon entry into study)

Subjects will be asked to rate their anticipated anxiety and pain at the time of uterine aspiration by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=62 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline Expected Pain	67.2 mm Standard Deviation 19.7	69.2 mm Standard Deviation 17.8
Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline Expected Anxiety	77.5 mm Standard Deviation 20.6	74.2 mm Standard Deviation 20.1

SECONDARY outcome

Timeframe: upon entering procedure room (30-60 minutes after premedication)

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subjects will be asked to rate anxiety and pain upon entering procedure room by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Perception of Pain and Anxiety Upon Entering Procedure Room Anxiety at Room Entry	51.4 mm Standard Deviation 25.4	34.5 mm Standard Deviation 22.9
Subject Perception of Pain and Anxiety Upon Entering Procedure Room Pain at Room Entry	17.5 mm Standard Deviation 21.1	10.1 mm Standard Deviation 15.4

SECONDARY outcome

Timeframe: 30 minutes post operatively

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subjects will be asked to rate anxiety and pain 30 minutes post-operatively by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Perception of Pain and Anxiety Post Procedure Anxiety Post Procedure	20.9 mm Standard Deviation 22.6	14.4 mm Standard Deviation 13.5
Subject Perception of Pain and Anxiety Post Procedure Pain Post Procedure	34.7 mm Standard Deviation 23.3	37.1 mm Standard Deviation 24.6

SECONDARY outcome

Timeframe: prior to starting pelvic exam (30-60 minutes after premedication)

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subjects will be asked to rate anxiety prior to starting pelvic exam by marking along a mm Visual Analog Scale, with 0mm being No Anxiety and 100mm being Worst Imaginable Anxiety

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Perception of Anxiety With Patient Positioning Procedure	56.6 mm Standard Deviation 26.4	45.4 mm Standard Deviation 26.3

SECONDARY outcome

Timeframe: with cervical dilation (30-60 minutes after premedication)

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subjects will be asked to rate pain at the time of cervical dilation by marking along a mm Visual Analog Scale, with 0mm being No Pain and 100mm being Worst Imaginable Pain

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Perception of Pain During Cervical Dilation	73.0 mm Standard Deviation 21.2	69.3 mm Standard Deviation 19.9

SECONDARY outcome

Timeframe: Baseline (upon entry into study)

To measure the mean State-Trait Anxiety Inventory (STAI) Form Y-1 for anxiety. State anxiety items include: "I am tense; I am worried" and "I feel calm; I feel secure." Trait anxiety items include: "I worry too much over something that really doesn't matter" and "I am content; I am a steady person." Each type of anxiety has its own 4-point scale of 20 different questions that are scored. The 4-point scale for S-anxiety is as follows: 1.) not at all, 2.) somewhat, 3.) moderately so, 4.) very much so. The 4-point scale for T-anxiety is as follows: 1.) almost never, 2.) sometimes, 3.) often, 4.) almost always. Scores range from 20 to 80, with higher scores indicate greater anxiety. State anxiety items and Trait anxiety items were each summed in assessment to provide two total scores for each participant, a State anxiety score and a Trait anxiety score. Mean and standard deviation of total scores for each group are reported.

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=62 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
State-Trait Anxiety Inventory for Anxiety at Baseline State anxiety level	50.8 units on a scale Standard Deviation 11.0	51.3 units on a scale Standard Deviation 9.7
State-Trait Anxiety Inventory for Anxiety at Baseline Trait anxiety level	40.1 units on a scale Standard Deviation 10.8	38.6 units on a scale Standard Deviation 9.7

SECONDARY outcome

Timeframe: 30 minutes post-operatively

To assess whether oral midazolam is associated with differences in overall patient satisfaction with pain and anxiety control and abortion experience at 30 min postoperatively as measured by a mm Visual Analog Scale with 0mm being Not At All Satisfied and 100mm being Very Satisfied

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively Satisfaction with anxiety control (100-mm VAS)	56.1 mm on a 100 mm Visual Analog Scale Standard Deviation 29.6	68.9 mm on a 100 mm Visual Analog Scale Standard Deviation 24.7
Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively Satisfaction with pain control (100-mm VAS)	43.2 mm on a 100 mm Visual Analog Scale Standard Deviation 30.7	50.0 mm on a 100 mm Visual Analog Scale Standard Deviation 27.3

SECONDARY outcome

Timeframe: 1-3 days post-operatively

To assess whether oral midazolam is associated with differences in overall patient satisfaction with pain and anxiety control and abortion experience at 1-3 days postoperatively as measured by a mm VAS with 0mm being Not At All Satisfied and 100mm being Very Satisfied

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure Satisfaction with anxiety control (100-mm VAS)	50.2 mm on a 100 mm Visual Analog Scale Standard Deviation 31.7	64.7 mm on a 100 mm Visual Analog Scale Standard Deviation 28.2
Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure Satisfaction with pain control (100-mm VAS)	36.6 mm on a 100 mm Visual Analog Scale Standard Deviation 30.8	48.2 mm on a 100 mm Visual Analog Scale Standard Deviation 30.1

SECONDARY outcome

Timeframe: 30 minutes postoperatively

To assess the extent of amnesia 30 min postoperatively as measured by ability to recall procedure using 4-point scale (0 = unable to recall any proportion of the procedure, 1 = able to recall and describe some portions of the procedure, but overall has minimal recall of the procedure, 2 = able to recall and describe most of the procedure, but admits to inability to recall some portion of the procedure, 3 = able to recall and describe the entire procedure).

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Extent of Amnesia Using Amnesia Score Partial to complete amnesia (score 0,1,2)	16 Participants	31 Participants
Subject Extent of Amnesia Using Amnesia Score No Amnesia (score 3)	45 Participants	30 Participants

SECONDARY outcome

Timeframe: 1-3 days postoperatively

To assess the extent of amnesia 1-3 days postoperatively as measured by 100mm Visual Analog Scale with 0mm being Remember Nothing and 100mm being Remember Everything.

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=41 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=44 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Extent of Amnesia	91.5 mm Standard Deviation 12.8	61.3 mm Standard Deviation 25.8

SECONDARY outcome

Timeframe: 30-60 minutes after premedication

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subject extent of sedation 30-60 minutes after premedication, just prior to procedure as measured by the 6-point Ramsay Scale (1 = patient anxious agitated, or restless; 2 = patient cooperative, oriented, and tranquil; 3 = patient asleep, responds to commands only; 4 = patient asleep, responds to gentle shaking, light glabellar tap, or loud auditory stimulus; 5 = patient asleep, responds to noxious stimuli such as firm nail bed pressure; 6 = patient asleep, has no response to firm nail bed pressure or other noxious stimuli)

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Extent of Sedation 1	11 Participants	10 Participants
Subject Extent of Sedation 2	50 Participants	51 Participants
Subject Extent of Sedation 3	0 Participants	1 Participants
Subject Extent of Sedation 4 or greater	0 Participants	0 Participants

SECONDARY outcome

Timeframe: intraoperatively (30-60 minutes after premedication)

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subject heart rate will be assessed for the duration of the procedure

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Vital Signs (Heart Rate)	80 bmp Interval 51.0 to 126.0	78.5 bmp Interval 50.0 to 137.0

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Population: 1 subject in the placebo group did not complete the study after changing mind to have abortion. Baseline information and characteristics on that subject was still collected and included where applicable in study outcomes and data.

Subject vital signs (heart rate) will be assessed 30 minutes postoperatively

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Vital Signs (Heart Rate) 30 Minutes Postprocedure	70.1 bpm Standard Deviation 12.4	72 bpm Standard Deviation 11.8

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Subject nausea will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Nausea 30 Minutes Postprocedure	9.5 100-mm visual analog sclae for nausea Interval 0.0 to 80.0	3.5 100-mm visual analog sclae for nausea Interval 0.0 to 71.0

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Number of patient's who could correctly determine if they received study drug or placebo when asked

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject's Correct Identification of Receiving Midazolam or Placebo	43 Participants	48 Participants

SECONDARY outcome

Timeframe: intraoperatively (30-60 minutes after premedication)

Subject oxygenation status will be assessed for the duration of the procedure

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Vital Signs (Oxygenation Saturation)	98.3 percent saturation Standard Deviation 1.2	98.1 percent saturation Standard Deviation 1.0

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Subject vital signs (oxygenation saturation) will be assessed 30 minutes postoperatively

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Vital Signs (Oxygenation Saturation) 30 Minutes Postprocedure	98.3 percent saturation Standard Deviation 1.2	98.1 percent saturation Standard Deviation 1.0

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Subject sleepiness will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Subject Sleepiness 30 Minutes Postprocedure	40.1 units on a scale Standard Deviation 29.3	56.6 units on a scale Standard Deviation 24.6

SECONDARY outcome

Timeframe: 30 minutes postoperatively

Population: One participant in the Midazolam group left the study. One participant in the placebo group decided not to have the procedure.

Subjects will be assessed 30 minutes postoperatively for need of additional pain medications.

Outcome measures

Measure	Placebo-cherry Syrup and Ibuprofen n=61 Participants 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=61 Participants 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Number of Participants With Need for Additional Postoperative Pain Medication Ondansetron	3 Participants	2 Participants
Number of Participants With Need for Additional Postoperative Pain Medication Hydrocodone/acetaminophen	2 Participants	1 Participants

Adverse Events

Placebo-cherry Syrup and Ibuprofen

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Midazolam and Ibuprofen

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo-cherry Syrup and Ibuprofen n=62 participants at risk 5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Placebo-Cherry syrup: 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine	Midazolam and Ibuprofen n=62 participants at risk 5 mL oral midazolam oral syrup (2 mg/mL) and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine Midazolam: 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure Ibuprofen: 800 mg oral ibuprofen 30-60 minutes prior to procedure Lidocaine: injection of 20 mL 1% lidocaine without epinephrine
Surgical and medical procedures Reaspiration	3.2% 2/62 • Number of events 2	1.6% 1/62 • Number of events 1
Surgical and medical procedures Cervical laceration	0.00% 0/62	1.6% 1/62 • Number of events 1
Surgical and medical procedures Hemorrhage	0.00% 0/62	1.6% 1/62 • Number of events 1

Additional Information

Lisa Bayer, MD

Oregon Health and Science University

Phone: 503-494-3666

Email: whru@gmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place