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24-hour Mifepristone and Buccal Versus Mifepristone and Vaginal Misoprostol for Cervical Preparation for D&E

A Randomized Double-blinded Comparison of 24-hour Interval-Mifepristone and Buccal Misoprostol Versus Mifepristone and Vaginal Misoprostol for Cervical Preparation in Second-Trimester Surgical Abortion

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03134183
Enrollment
70
Registered
2017-04-28
Start date
2016-11-19
Completion date
2017-08-01
Last updated
2018-07-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Abortion, Second Trimester

Keywords

D&E, dilation and evacuation, abortion, second trimester, mifepristone, misoprostol

Brief summary

This study aims to compare mifepristone and buccal misoprostol to mifepristone and vaginal misoprostol for cervical preparation for second trimester dilation and evacuation (D&E).

Detailed description

Standard of care for cervical preparation prior to second trimester surgical abortion has traditionally been a pelvic exam with speculum, a paracervical block with lidocaine, and placement of a number of osmotic dilators through the cervical canal. Dilators obtain maximal expansion within 4-6 hours and patients experience cramping with this process. This cervical preparation allows for a faster procedure for the patient (limiting time for anesthesia) and an easier procedure for the provider (decreasing necessity for further dilation, decreasing risk of cervical laceration, and decreasing blood loss). Following cervical preparation, trained providers use instruments to remove the pregnancy per standard of care. Several studies have examined the use of medication (mifepristone and/or misoprostol) to dilate the cervix as an alternative to osmotic dilators . Patients prefer medication to dilators as medication is associated with less discomfort. Medications alone can achieve adequate cervical preparation but the optimal timing and routes of these medications has not been sufficiently evaluated. The addition of mifepristone, a progesterone antagonist, to a misoprostol regimen has been shown to significantly decrease the medication-to-abortion interval in second-trimester induction terminations. Vaginal administration has demonstrated improved dilation as compared to buccal administration but it is known that patients prefer buccal administration. A comparison of mifepristone and vaginal versus mifepristone and buccal misoprostol has not been studied prior to second-trimester surgical abortion. A review of cervical preparation for second-trimester D&E did not recommend mifepristone and misoprostol for cervical priming due to high rates of pre-procedural expulsions. However, the primary basis for this conclusion is a trial in which the 48-hour interval between the medications accounts for the high out-of-facility expulsion risk. A retrospective cohort of over 200 women between 14 and 19 6/7 weeks gestation showed no difference in difficulty of cervical dilation for patients receiving mifepristone 24-48 hours misoprostol as compared to osmotic dilators prior to surgical abortion. Two out of facility expulsions occurred in the mifepristone-misoprostol arms but the timing of medication to expulsion interval is not reported. More recent studies have limited the timing of mifepristone to 24 hours or less prior to procedure. Mifepristone only has been shown to provide adequate cervical dilation as compared to osmotic dilators to 16 weeks gestation with noninferiority design to detect a 3-minute difference in procedure time. A 24-hour interval between 200mg mifepristone and 400mcg buccal misoprostol has been shown as non-inferior to osmotic dilators for total procedure time for 15-18 week surgical abortions. Mifepristone and one-set of osmotic dilators was found to be non-inferior for total procedure time as compared to two sets of osmotic dilators for surgical abortion 19-23 6/7 weeks gestation. The addition of mifepristone has benefit as a cervical priming agent as an adjunct or alternative to osmotic dilators for surgical abortion, but it is not known whether the addition of vaginal versus buccal misoprostol changes cervical dilation and thus procedure time outcomes.

Interventions

DRUGVaginal Misoprostol

Mifepristone 200mg orally 20-24 hours prior and misoprostol 400mcg (two 200mcg tablets) vaginally 1-2 hours prior and placebo (buccal mint powder) buccally 1-2 hours prior to D&E

Mifepristone 200mg orally 20-24 hours prior and misoprostol 400mcg (two 200mcg tablets) ground with mint into buccal powder and placebo (two lactose tablets designed to appear similar to misoprostol) vaginally 1-2 hours prior to D&E

Sponsors

Virginia Commonwealth University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Masking description

Computer-generated randomization will be utilized to assign treatment arms and the vaginal misoprostol and buccal placebo and buccal misoprostol and vaginal placebo will be prepared according to randomization scheme by the research pharmacy in opaque-sealed envelopes as to blind participants and providers.

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes

Inclusion criteria

* The study will enroll healthy English or Spanish-speaking women, over 18 years of age, eligible for non-urgent D&E at 16 0/7 weeks to 20 6/7 weeks gestation, confirmed by sonogram, and willing/able to undergo informed consent.

Exclusion criteria

* Emergent need for D&E, intrauterine infection, fetal demise, molar pregnancy, intolerance, allergy or contraindication to mifepristone or misoprostol

Design outcomes

Primary

MeasureTime frameDescription
Procedure TimeAt end of procedureTime from initial uterine instrumentation to speculum out

Secondary

MeasureTime frameDescription
Cervical DilationAt end of procedurePratt Dilator initially accepted without resistance starting from 65 and working down

Countries

United States

Participant flow

Participants by arm

ArmCount
Vaginal Misoprostol
Intervention is misoprostol versus placebo 400mcg misoprostol formulated within cocoa butter suppository Vaginal Misoprostol: Mifepristone 200mg orally 20-24 hours prior and misoprostol 400mcg (two 200mcg tablets) vaginally 1-2 hours prior and placebo (buccal mint powder) buccally 1-2 hours prior to D&E
35
Buccal Misoprostol
Intervention is misoprostol versus placebo 400mcg misoprostol formulated within mint flavored powder Buccal Misoprostol: Mifepristone 200mg orally 20-24 hours prior and misoprostol 400mcg (two 200mcg tablets) ground with mint into buccal powder and placebo (two lactose tablets designed to appear similar to misoprostol) vaginally 1-2 hours prior to D&E
33
Total68

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyWithdrawal by Subject11

Baseline characteristics

CharacteristicBuccal MisoprostolTotalVaginal Misoprostol
Age, Customized
18-24
16 Participants29 Participants13 Participants
Age, Customized
25-29
6 Participants15 Participants9 Participants
Age, Customized
30-34
7 Participants11 Participants4 Participants
Age, Customized
35+
5 Participants15 Participants10 Participants
Race and Ethnicity Not Collected0 Participants
Region of Enrollment
United States
33 Participants68 Participants35 Participants
Sex: Female, Male
Female
33 Participants68 Participants35 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 350 / 33
other
Total, other adverse events
1 / 360 / 34
serious
Total, serious adverse events
0 / 350 / 33

Outcome results

Primary

Procedure Time

Time from initial uterine instrumentation to speculum out

Time frame: At end of procedure

ArmMeasureValue (MEAN)Dispersion
Vaginal MisoprostolProcedure Time9.5 minutesStandard Deviation 5
Buccal MisoprostolProcedure Time9.9 minutesStandard Deviation 4
Secondary

Cervical Dilation

Pratt Dilator initially accepted without resistance starting from 65 and working down

Time frame: At end of procedure

ArmMeasureValue (MEAN)Dispersion
Vaginal MisoprostolCervical Dilation49.6 French circumference in millimetersStandard Deviation 10
Buccal MisoprostolCervical Dilation46.2 French circumference in millimetersStandard Deviation 11

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026