Clinical trial NCT02141555: Comparing Buccal and Vaginal Misoprostol in Management of Early Pregnancy Loss
Official title: Comparing Buccal and Vaginal Misoprostol in Management of Early Pregnancy Loss: a Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Spontaneous Abortion in First Trimester
Keywords: misoprostol, early pregnancy loss, missed abortion
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2014-05-19
Enrollment: 4
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: First trimester miscarriages are common. When the failed pregnancy does not pass spontaneously on its own, it is called a missed abortion. There are several ways in which missed abortions are managed, one of which involves administering a medication called misoprostol which causes uterine contractions inducing expulsion of the failed pregnancy. Misoprostol can be administered in multiple ways but has been traditionally inserted vaginally when used for management of missed abortions. Some studies have shown that some women are not comfortable with vaginal insertion of misoprostol and prefer oral administration. Buccal misoprostol is a way of administering misoprostol by having the patients insert the tablets of misoprostol between their gum and cheek, letting it dissolve for 30 minutes, then swallowing the remaining remnants. Buccal misoprostol is used safely in medical abortion. In fact a study by Fjerstad et al (2009), found a decrease in infection rate for medical abortion when misoprostol administration was switched from vaginal to buccal route combined with routine administration of doxycycline. The efficacy of using buccal misoprostol to treat missed abortions has not been studied previously to the investigators' knowledge. In this pilot study, investigators aim to test the hypotheses that buccal misoprostol is equally effective as vaginal misoprostol in the medical management of early pregnancy loss. As secondary outcomes, investigators suspect that buccal misoprostol may be associated with higher rates of gastrointestinal side effect but that patient satisfaction will remain equally as high for buccal misoprostol as for vaginal misoprostol.

Detailed description: Randomization:

Women who present to University of California, San Diego (UCSD) Medical Offices South clinic for evaluation and management of missed abortion will all be sent to the lab prior to the clinic visit for a type and screen and hemogram to determine blood type and hemoglobin level as is the current standard of care. Each woman will then be screened by a physician. The physician will notify a co-investigator of eligible patients who are interested in participating in the study. The co-investigator will consent the patient for the study. Once the written consent is obtained, patient will be asked to fill out an intake survey to obtain demographic information. Participants will be randomized into either the vaginal or buccal misoprostol group with a block size of four. Assignments will be concealed in sequentially numbered sealed opaque envelope. The envelope will be opened by the co-investigator who will reveal the route of misoprostol to the patient and review the written instructions on how to take the medication appropriately. Given the different routes of administration, neither the patient nor the provider will be blinded. Given that one of the secondary outcomes of interest was patient satisfaction based on the different route of administration, decision was made to not use placebo pills which could have been used to do a double-blinded study.

Intervention:

Dose of Misoprostol for both treatment groups: 800 micrograms administered as four tablets of 200 micrograms.

Currently, the standard of care is to prescribe vaginal misoprostol 800 mcg for women with an early pregnancy failure desiring medical management. The only "intervention" in this study is to change the route of administration from vaginal to buccal for the women randomized to this group. The dose of misoprostol, follow up plan (including ultrasound) and prescription for pain medications (described below) is unchanged from the current standard of care. Participants randomized to the vaginal misoprostol group will be instructed to insert four misoprostol tablets (total of 800 micrograms) deeply into the vagina with their fingers. Participants randomized to the buccal misoprostol group will be instructed to place two tablets of misoprostol between their gum and cheek on each side (total 800 micrograms), then swish and swallow the remnants after 30 minutes. If the patient is Rh negative, the patient will be given a dose of rhogam 300 mcg at the initial visit which is the current standard of care.

Patients will be prescribed an additional dose of misoprostol 800 mcg that they can take at their own discretion in the absence of vaginal bleeding 48 hours from initial dose using the same route of administration as the first dose. All participants will be prescribed ibuprofen with instructions to take 600 mg every 6 hours as needed for pain and a narcotic medication for breakthrough pain. The cost of these medications will be fully covered by the participant's insurance with no additional cost to the participant.

Follow up will be a clinic visit scheduled one week from the from the initial visit at UCSD Medical Offices South Clinic which time the participant will fill out a follow up survey assessing the participant's satisfaction and side effects experienced. The provider will also fill out a survey at this 1-week follow up visit assessing the success of the misoprostol in achieving a complete abortion. The participant's involvement in the study will conclude at this end of this one-week follow up visit.

Participant Commitment:

The research will require the following additional time commitment from participant in addition to the standard clinic visit:

1. Initial Visit: An additional 20 minutes will be required to review the study consent, randomize to the vaginal or buccal misoprostol group, and have the patient fill out a short intake survey.
2. Follow-up visit: The follow up visit will take one week from time of initial visit. An additional 10 minutes will be required to fill out the follow up survey. The participant's involvement in the study will conclude with this visit.

Eligibility criteria: Inclusion Criteria:

* Women ages 18-50 who are English or Spanish speaking
* First trimester pregnancy (less than 13 weeks and 0 days)
* Desires medical management of an early pregnancy loss with misoprostol
* Diagnosed with an early pregnancy failure by UCSD Radiology or diagnosed early pregnancy failure defined by any of the following criteria (Bourne 2013):

  * Crown-rump length \> 7mm with no cardiac activity
  * Mean gestational sac diameter of \> 25 mm and no embryo
  * Absence of an embryo with heartbeat \> 2 weeks after a scan showing a gestational sac without a yolk sac
  * Absence of embryo with heartbeat \> 11 days after a scan showing a gestational sac with a yolk sac

Exclusion Criteria:

* Evidence of infection, acute hemorrhage, or hemodynamic instability
* Hemoglobin less than 9.5 including use of point of care Hgb testing
* Known allergy to misoprostol
* Underwent surgical or medical abortion during current pregnancy
* Currently breastfeeding
* Currently has intrauterine device in place
* Suspicion of ectopic or gestational trophoblastic disease
* History of clotting disorder or on anticoagulant therapy (excluding aspirin)
* Unreliable for follow up

Primary outcomes:
measure: Patient Enrollment
timeFrame: One year
Secondary outcomes:
measure: Number of Participants With Complete Abortion
timeFrame: one week
measure: Number of Participants Who Answered 1 or 2 on a Scale of Satisfaction With the Procedure
timeFrame: one week
measure: Number of Participants Reporting 2 or 3 on a Scale of Medication Side Effects
timeFrame: one week
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Universty of California San Diego Perlman Clinic
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Offices South Clinic
state: California
Study officials:
affiliation: University of California, San Diego
name: Janie Pak, MD, MPH
role: STUDY_DIRECTOR
affiliation: University of California, San Diego
name: Sheila Mody, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aronsson A, Fiala C, Stephansson O, Granath F, Watzer B, Schweer H, Gemzell-Danielsson K. Pharmacokinetic profiles up to 12 h after administration of vaginal, sublingual and slow-release oral misoprostol. Hum Reprod. 2007 Jul;22(7):1912-8. doi: 10.1093/humrep/dem098. Epub 2007 May 8.
citation: Doubilet PM, Benson CB, Bourne T, Blaivas M; Society of Radiologists in Ultrasound Multispecialty Panel on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy; Barnhart KT, Benacerraf BR, Brown DL, Filly RA, Fox JC, Goldstein SR, Kendall JL, Lyons EA, Porter MB, Pretorius DH, Timor-Tritsch IE. Diagnostic criteria for nonviable pregnancy early in the first trimester. N Engl J Med. 2013 Oct 10;369(15):1443-51. doi: 10.1056/NEJMra1302417. No abstract available.
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citation: Fjerstad M, Trussell J, Sivin I, Lichtenberg ES, Cullins V. Rates of serious infection after changes in regimens for medical abortion. N Engl J Med. 2009 Jul 9;361(2):145-51. doi: 10.1056/NEJMoa0809146.
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citation: Middleton T, Schaff E, Fielding SL, Scahill M, Shannon C, Westheimer E, Wilkinson T, Winikoff B. Randomized trial of mifepristone and buccal or vaginal misoprostol for abortion through 56 days of last menstrual period. Contraception. 2005 Nov;72(5):328-32. doi: 10.1016/j.contraception.2005.05.017. Epub 2005 Aug 9.
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