Evaluation of Oral Midazolam in First-trimester Surgical Abortions

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Evaluation of Oral Midazolam for Anxiety and Pain in First-trimester Surgical Abortion: a Randomized Controlled Trial

Conditions
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Pain, Anxiety, Nausea

Intervention / Treatment
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* Drug: Midazolam
* Drug: Ibuprofen
* Other: Placebo-Cherry syrup
* Drug: Lidocaine


Participation Criteria
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Eligibility Criteria
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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))

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo-cherry syrup and ibuprofen<br>5 mL oral placebo-cherry syrup and 800 mg oral ibuprofen 30-60 minutes prior to procedure 20 mL injection 1% lidocaine without epinephrine | Drug: Ibuprofen<br>* 800 mg oral ibuprofen 30-60 minutes prior to procedure<br>* Other names: Motrin;Other: Placebo-Cherry syrup<br>* 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure<br>* Other names: placebo cherry syrup;Drug: Lidocaine<br>* injection of 20 mL 1% lidocaine without epinephrine<br>* Other names: lidocaine injection;|
| Active Comparator: Midazolam and ibuprofen<br>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 | Drug: Midazolam<br>* 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure<br>* Other names: Versed;Drug: Ibuprofen<br>* 800 mg oral ibuprofen 30-60 minutes prior to procedure<br>* Other names: Motrin;Drug: Lidocaine<br>* injection of 20 mL 1% lidocaine without epinephrine<br>* Other names: lidocaine injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Perception of Pain and Anxiety During Uterine Aspiration | 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 | at time of uterine aspiration (30-60 minutes after premedication) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline | 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 | Baseline (upon entry into study) | 
| Subject Perception of Pain and Anxiety Upon Entering Procedure Room | 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 | upon entering procedure room (30-60 minutes after premedication) | 
| Subject Perception of Pain and Anxiety Post Procedure | 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 | 30 minutes post operatively | 
| Subject Perception of Anxiety With Patient Positioning Procedure | 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 | prior to starting pelvic exam (30-60 minutes after premedication) | 
| Subject Perception of Pain During Cervical Dilation | 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 | with cervical dilation (30-60 minutes after premedication) | 
| State-Trait Anxiety Inventory for Anxiety at Baseline | 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. | Baseline (upon entry into study) | 
| Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively | 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 | 30 minutes post-operatively | 
| Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure | 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 | 1-3 days post-operatively | 
| Subject Extent of Amnesia Using Amnesia Score | 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). | 30 minutes postoperatively | 
| Subject Extent of Amnesia | 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. | 1-3 days postoperatively | 
| Subject Extent of Sedation | 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) | 30-60 minutes after premedication | 
| Subject Vital Signs (Heart Rate) | Subject heart rate will be assessed for the duration of the procedure | intraoperatively (30-60 minutes after premedication) | 
| Subject Vital Signs (Heart Rate) 30 Minutes Postprocedure | Subject vital signs (heart rate) will be assessed 30 minutes postoperatively | 30 minutes postoperatively | 
| Subject Nausea 30 Minutes Postprocedure | Subject nausea will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable | 30 minutes postoperatively | 
| Subject's Correct Identification of Receiving Midazolam or Placebo | Number of patient's who could correctly determine if they received study drug or placebo when asked | 30 minutes postoperatively | 
| Subject Vital Signs (Oxygenation Saturation) | Subject oxygenation status will be assessed for the duration of the procedure | intraoperatively (30-60 minutes after premedication) | 
| Subject Vital Signs (Oxygenation Saturation) 30 Minutes Postprocedure | Subject vital signs (oxygenation saturation) will be assessed 30 minutes postoperatively | 30 minutes postoperatively | 
| Subject Sleepiness 30 Minutes Postprocedure | Subject sleepiness will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable | 30 minutes postoperatively | 
| Number of Participants With Need for Additional Postoperative Pain Medication | Subjects will be assessed 30 minutes postoperatively for need of additional pain medications. | 30 minutes postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pain, anxiety, surgical abortion, midazolam, benzodiazepine