Evaluation of Oral Midazolam in First-trimester Surgical Abortions

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

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.

Study Overview

• Status: Completed
• Conditions: Pain; Nausea; Anxiety
• Intervention / Treatment: Drug: Ibuprofen; Other: Placebo-Cherry syrup; Drug: Lidocaine; Drug: Midazolam

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97206
      • Planned Parenthood Columbia Willamette

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 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	Drug: Ibuprofen; 800 mg oral ibuprofen 30-60 minutes prior to procedure; Other Names: Motrin; Other: Placebo-Cherry syrup; 5 mL oral placebo-cherry syrup 30-60 minutes prior to procedure; Other Names: placebo cherry syrup; Drug: Lidocaine; injection of 20 mL 1% lidocaine without epinephrine; Other Names: lidocaine injection
ACTIVE_COMPARATOR: 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	Drug: Ibuprofen; 800 mg oral ibuprofen 30-60 minutes prior to procedure; Other Names: Motrin; Drug: Lidocaine; injection of 20 mL 1% lidocaine without epinephrine; Other Names: lidocaine injection; Drug: Midazolam; 5 mL oral midazolam oral syrup (2 mg/mL) 30-60 minutes prior to procedure; Other Names: Versed

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oregon Health and Science University
• Investigators: Principal Investigator: Lisa Bayer, MD, Oregon Health and Science University

Publications and helpful links

General Publications

• Bayer LL, Edelman AB, Fu R, Lambert WE, Nichols MD, Bednarek PH, Miller K, Jensen JT. An Evaluation of Oral Midazolam for Anxiety and Pain in First-Trimester Surgical Abortion: A Randomized Controlled Trial. Obstet Gynecol. 2015 Jul;126(1):37-46. doi: 10.1097/AOG.0000000000000913.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): January 1, 2014

Study Registration Dates

• First Submitted: April 3, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (ESTIMATE): April 12, 2013

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 20, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: pain; midazolam; anxiety; surgical abortion; benzodiazepine
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Midazolam; Lidocaine; Ibuprofen
• Other Study ID Numbers: OHSU IRB 9064

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO