Comparing Buccal and Vaginal Misoprostol in Management of Early Pregnancy Loss

NCT02141555 | Completed Phase 2 Results DMC

• 1 other identifier: 140250
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

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.

Conditions

Spontaneous Abortion in First Trimester

Keywords

misoprostol, early pregnancy loss, missed abortion

Outcome Measures

Primary Outcomes (1)

• Patient Enrollment

  The percentage of women who are offered enrollment and accept.

  One year

Secondary Outcomes (3)

• Number of Participants With Complete Abortion

  one week

• Number of Participants Who Answered 1 or 2 on a Scale of Satisfaction With the Procedure

  one week

• Number of Participants Reporting 2 or 3 on a Scale of Medication Side Effects

  one week

Study Arms (2)

Vaginal misoprostol

ACTIVE COMPARATOR

Participants will insert four misoprostol tablets (total of 800 micrograms) deeply into the vagina with their fingers.

Drug: Vaginal Misoprostol

Buccal Misoprostol

EXPERIMENTAL

Participants will 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.

Drug: Buccal Misoprostol

Interventions

Vaginal Misoprostol DRUG

Misoprostol inserted into vagina

Also known as: Vaginal Cytotec

Vaginal misoprostol

Buccal Misoprostol DRUG

Misoprostol placed between the gum and cheek and allowed to dissolve for 30 minutes with the remnants swallowed after this time.

Also known as: Buccal Cytotec

Buccal Misoprostol

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (2)

Universty of California San Diego Perlman Clinic

La Jolla, California, 92037, United States

Location

University of California San Diego Medical Offices South Clinic

San Diego, California, 92103, United States

Location

Related Publications (15)

• 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.

  PMID: 17488782 BACKGROUND

• 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.

  PMID: 24106937 BACKGROUND

• Danielsson KG, Marions L, Rodriguez A, Spur BW, Wong PY, Bygdeman M. Comparison between oral and vaginal administration of misoprostol on uterine contractility. Obstet Gynecol. 1999 Feb;93(2):275-80. doi: 10.1016/s0029-7844(98)00436-0.

  PMID: 9932569 BACKGROUND

• 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.

  PMID: 19587339 BACKGROUND

• Jones RK, Kost K. Underreporting of induced and spontaneous abortion in the United States: an analysis of the 2002 National Survey of Family Growth. Stud Fam Plann. 2007 Sep;38(3):187-97. doi: 10.1111/j.1728-4465.2007.00130.x.

  PMID: 17933292 BACKGROUND

• Herting RL, Clay GA. Overview of clinical safety with misoprostol. Dig Dis Sci. 1985 Nov;30(11 Suppl):185S-193S. doi: 10.1007/BF01309407.

  PMID: 3932053 BACKGROUND

• Meckstroth KR, Whitaker AK, Bertisch S, Goldberg AB, Darney PD. Misoprostol administered by epithelial routes: Drug absorption and uterine response. Obstet Gynecol. 2006 Sep;108(3 Pt 1):582-90. doi: 10.1097/01.AOG.0000230398.32794.9d.

  PMID: 16946218 BACKGROUND

• 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.

  PMID: 16246656 BACKGROUND

• Tang OS, Gemzell-Danielsson K, Ho PC. Misoprostol: pharmacokinetic profiles, effects on the uterus and side-effects. Int J Gynaecol Obstet. 2007 Dec;99 Suppl 2:S160-7. doi: 10.1016/j.ijgo.2007.09.004. Epub 2007 Oct 26.

  PMID: 17963768 BACKGROUND

• Saraiya M, Berg CJ, Shulman H, Green CA, Atrash HK. Estimates of the annual number of clinically recognized pregnancies in the United States, 1981-1991. Am J Epidemiol. 1999 Jun 1;149(11):1025-9. doi: 10.1093/oxfordjournals.aje.a009747.

  PMID: 10355378 BACKGROUND

• Schaff EA, DiCenzo R, Fielding SL. Comparison of misoprostol plasma concentrations following buccal and sublingual administration. Contraception. 2005 Jan;71(1):22-5. doi: 10.1016/j.contraception.2004.06.014.

  PMID: 15639067 BACKGROUND

• Schaff EA, Fielding SL, Westhoff C. Randomized trial of oral versus vaginal misoprostol at one day after mifepristone for early medical abortion. Contraception. 2001 Aug;64(2):81-5. doi: 10.1016/s0010-7824(01)00229-3.

  PMID: 11704083 BACKGROUND

• Sedgh G, Henshaw S, Singh S, Ahman E, Shah IH. Induced abortion: estimated rates and trends worldwide. Lancet. 2007 Oct 13;370(9595):1338-45. doi: 10.1016/S0140-6736(07)61575-X.

  PMID: 17933648 BACKGROUND

• Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, Armstrong EG, Nisula BC. Incidence of early loss of pregnancy. N Engl J Med. 1988 Jul 28;319(4):189-94. doi: 10.1056/NEJM198807283190401.

  PMID: 3393170 BACKGROUND

• Winikoff B, Dzuba IG, Creinin MD, Crowden WA, Goldberg AB, Gonzales J, Howe M, Moskowitz J, Prine L, Shannon CS. Two distinct oral routes of misoprostol in mifepristone medical abortion: a randomized controlled trial. Obstet Gynecol. 2008 Dec;112(6):1303-1310. doi: 10.1097/AOG.0b013e31818d8eb4.

  PMID: 19037040 BACKGROUND

MeSH Terms

Conditions

Abortion, Spontaneous; Abortion, Missed

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Limitations and Caveats

Due to the small number of participants, no conclusions could be drawn and a larger study was not done.

Results Point of Contact

• Title: Dr. Sheila Mody
• Organization: University of California, San Diego

smody@ucsd.edu

Study Officials

• Janie Pak, MD, MPH

  University of California, San Diego

  STUDY DIRECTOR

• Sheila Mody, MD, MPH

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Adjunct Professor, Section of Family Planning

Study Record Dates

• First Submitted: May 10, 2014
• First Posted: May 19, 2014
• Study Start: August 1, 2014
• Primary Completion: April 1, 2015
• Study Completion: June 1, 2016
• Last Updated: August 15, 2019
• Results First Posted: August 15, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)