Evaluation of Oral Midazolam in First-trimester Surgical Abortions

Phase 4

Completed

Conditions: Pain
Anxiety
Nausea

Interventions: Drug: Ibuprofen
Drug: Midazolam
Other: Placebo-Cherry syrup
Drug: Lidocaine

Registration Number: NCT01830881

Lead Sponsor: Oregon Health and Science University

Brief Summary: The purpose of this study is to determine the level of pain, anxiety and side effects that women experience with a surgical abortion and the effect that the anti-anxiety medication, midazolam, might have when used along with ibuprofen and a paracervical block (PCB) instead of the standard pain treatment of only ibuprofen and a PCB.

Detailed Description: Women in the study will be randomized to receive either midazolam or placebo. Every participant will still receive the standard oral medications for pain (ibuprofen) as well as an injection of numbing medicine (lidocaine) near the cervix (PCB). The co-primary outcomes are patient perception of anxiety and pain with uterine aspiration reported on a 100 mm visual analogue scale (VAS). Secondary outcomes include reported anxiety and pain at time points before, during, and after the procedure, as well as subject satisfaction with anxiety and pain control and overall abortion experience. Due to the dose-dependent anterograde amnesic effect of midazolam, we will also investigate the effects on memory and recall, which has not previously been studied. In addition, we will also collect data on side effects frequently associated with oral midazolam such as nausea and sleepiness. Women will also be responsible for completing a one-page survey 1-3 days after the procedure visit and return it by mail using a pre-addressed and stamped envelope.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 124

Inclusion Criteria

Aged 18 years or older
Voluntarily requesting surgical pregnancy termination
Pregnancy with intrauterine gestational sac between 6 0/7 and 10 6/7 weeks gestation, dated by ultrasound
Eligible for suction aspiration
English or Spanish speaking
Good general health
Able and willing to give informed consent and agree to terms of the study
Have assistance home; no driving for 24 hours

Exclusion Criteria

- Gestational ages 11 0/7 weeks or more
Gestational age less than 6 0/7 weeks
Incomplete abortion
Premedication with misoprostol
Use of narcotic pain or anti-anxiety medication within past 24 hours
Use of heroin or methadone within last 3 months
Chronic alcoholism or alcohol intoxication within past 24 hours
Requested narcotics or Intravenous sedation (prior to randomization)
Allergic reaction or allergy to cherry/cherry flavoring or lidocaine or non-steroidal anti-inflammatory drugs (NSAIDs)
Allergic reaction or sensitivity to benzodiazepines including hyperactive or aggressive behavior (paradoxical reaction)
Medical problem necessitating inpatient procedure
Untreated acute cervicitis or pelvic inflammatory disease
Known acute narrow-angle glaucoma
Weighing less than 100 lb (45 kg)
Use of potent medications interfering with microsomal metabolism within past 48 hours (carbamazepine (Tegretol), cimetidine (Tagamet), diltiazem (Cardizem), erythromycin, fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral), phenobarbital, phenytoin (Dilantin), nelfinavir, ranitidine (Zantac), rifampin (Rifadin), ritonavir (Norvir), saquinavir, verapamil (Calan))

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo-cherry syrup and ibuprofen	Placebo-Cherry syrup	5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine
placebo-cherry syrup and ibuprofen	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
Midazolam and ibuprofen	Midazolam	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
placebo-cherry syrup and ibuprofen	Lidocaine	5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine
Midazolam and ibuprofen	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 and ibuprofen	Lidocaine	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

Primary Outcome Measures

Name	Time	Method
Subject Perception of Pain and Anxiety During Uterine Aspiration	at time of uterine aspiration (30-60 minutes after premedication)	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

Secondary Outcome Measures

Name	Time	Method
Subject Perception of Pain and Anxiety Upon Entering Procedure Room	upon entering procedure room (30-60 minutes after premedication)	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
Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure	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
Subject Nausea 30 Minutes Postprocedure	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
Subject's Correct Identification of Receiving Midazolam or Placebo	30 minutes postoperatively	Number of patient's who could correctly determine if they received study drug or placebo when asked
Subject Vital Signs (Oxygenation Saturation)	intraoperatively (30-60 minutes after premedication)	Subject oxygenation status will be assessed for the duration of the procedure
Subject Vital Signs (Oxygenation Saturation) 30 Minutes Postprocedure	30 minutes postoperatively	Subject vital signs (oxygenation saturation) will be assessed 30 minutes postoperatively
Number of Participants With Need for Additional Postoperative Pain Medication	30 minutes postoperatively	Subjects will be assessed 30 minutes postoperatively for need of additional pain medications.
Subject Perception of Pain and Anxiety Post Procedure	30 minutes post operatively	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
Subject Vital Signs (Heart Rate)	intraoperatively (30-60 minutes after premedication)	Subject heart rate will be assessed for the duration of the procedure
Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline	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
State-Trait Anxiety Inventory for Anxiety at Baseline	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.
Subject Extent of Amnesia Using Amnesia Score	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).
Subject Extent of Amnesia	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.
Subject Perception of Anxiety With Patient Positioning Procedure	prior to starting pelvic exam (30-60 minutes after premedication)	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
Subject Perception of Pain During Cervical Dilation	with cervical dilation (30-60 minutes after premedication)	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
Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively	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
Subject Vital Signs (Heart Rate) 30 Minutes Postprocedure	30 minutes postoperatively	Subject vital signs (heart rate) will be assessed 30 minutes postoperatively
Subject Extent of Sedation	30-60 minutes after premedication	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)
Subject Sleepiness 30 Minutes Postprocedure	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