Sublingual Versus Vaginal Misoprostol for Labor Induction at Term
Information source: American University of Beirut Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Induction of Labor
Intervention: Misoprostol (Cytotec®) (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: American University of Beirut Medical Center Official(s) and/or principal investigator(s): Anwar H Nassar, MD, Principal Investigator, Affiliation: American University of Beirut Medical Center
Summary
Misoprostol (Cytotec®) is a synthetic prostaglandin E1 analog that has been marketed in the
United States since 1988 as a gastric cytoprotective agent. In contradistinction to
prostaglandin E2 preparations (dinoprostone, Prepidil, Cervidil), misoprostol is inexpensive
and available in scored tablets that can be broken and inserted vaginally. Despite a focused
campaign by the manufacturer to curtail its use in obstetric practice, misoprostol has, over
the past several years, gained widespread acceptance as both a labor induction and a
cervical ripening agent. Such off-label indication has been endorsed by the American College
of Obstetricians and Gynecologists and other medical bodies. Recently, FDA approved a new
label for the use of cytotec during pregnancy which removed pregnancy as a contraindication
for its use. Vaginal administration seems to be more efficacious than when given orally,
although there is the worry of uterine tachysystole and hyperstimulation with vaginal doses
> 50-µg. The use of sublingual misoprostol for cervical ripening at term was recently
investigated in two studies that compared it to the oral route, on the assumption that the
sublingual route would have the higher efficacy of the vaginal route by avoiding the first
pass effects of the gastrointestinal and hepatic systems, while having lower
hyperstimulation rates by avoiding the direct effects on the cervix. In addition, the
sublingual route would combine an easier administration with the added advantage of no
restriction of mobility after administration. There has been no previous report in the
literature comparing the use of misoprostol given sublingually to that given vaginally for
the induction of labor at term. Our aim is to compare efficacy, safety and patient
satisfaction with misoprostol given vaginally (the current standard) to that given
sublingually.
Clinical Details
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The proportion of women satisfied with the route of administration of misoprostol.
Secondary outcome: The interval of induction to deliveryNumber of doses of misoprostol given Number of unsuccessful inductions Number of cesarean deliveries for fetal concerns The incidence of tachysystole
Detailed description:
Misoprostol, a synthetic prostaglandin E1 analog, has been given both orally and vaginally
for induction of labor in the third trimester. 1 Vaginal misoprostol has been shown to be
more efficacious than oral misoprostol in equivalent doses,2 although there is the worry of
uterine tachysystole and hyperstimulation with vaginal doses of 50 µg or higher. 2-4 The
higher efficacy after vaginal administration may be explained by the pharmacokinetics of the
drug. Zeiman et al5 showed that the systemic bioavailability of vaginally administered
misoprostol is 3 times higher than that after oral administration. Plasma concentrations of
its metabolite, misoprostol acid, peak one to two hours after vaginal application as
compared with the peak seen 30 minutes following oral administration, and although peak
levels are lower with the vaginal route, they are sustained longer and overall exposure to
the drug is increased, perhaps because of the presystemic gastrointestinal or hepatic
metabolism that occurs with the oral route. An additional explanation for the higher
efficacy could be that there is a direct effect on the cervix that initiates the physiologic
events that lead to increased uterine contractility. 6 However, there seems to be a trend
toward patient preference for the oral route. The sublingual route of administration has not
been reported in the literature prior to 2001. Since then and partly because of issues
relating to patient preference, investigators started studying the sublingual route of
administration of misoprostol. In theory, the sublingual route could mimic vaginal
administration pharmacokinetically, although there have been no such reported studies on
this route of administration.
It is speculated that sublingual misoprostol could combine the higher efficacy of the
vaginal route by avoiding gastrointestinal and hepatic metabolism, but it could have a more
restrained effect on uterine contractility by avoiding direct effects on both the uterus and
cervix. Therefore, in theory, the sublingual route may have lower hyperstimulation rates and
would have the advantage of a less invasive administration and lack of restriction of
mobility.
Although many studies have been published on the use of sublingual misoprostol for medical
abortion in the first and second trimesters, 7-11, only two studies (by the same group) have
compared sublingual to oral misoprostol, in different doses. 12,13 The 50-µg dose was chosen
because it is the dose most commonly used orally and vaginally in various studies reported
in the literature. 3,14 To the best of our knowledge, no study comparing sublingual to
vaginal misoprostol for labor induction at term has been previously published in the
literature. Therefore, this study, when completed will provide evidence on the relative
effect and safety profile of different routes of administration of misoprostol for labor
induction.
The aim of our study is to compare the efficacy of a 50-µg sublingual dose of misoprostol
administered at 4-hour intervals with an equivalent dose regimen administered vaginally in
women admitted for induction of labor for a medical or obstetric indication at term. In
addition, we want to assess the safety profile and patient acceptability of the 2 modes of
administration.
The study hypothesis is that the sublingual route of administration of misoprostol is as
effective as the vaginal route for induction of labor at term and is more acceptable to
patients as compared to vaginal misoprostol.
Eligibility
Minimum age: 16 Years.
Maximum age: 45 Years.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Live singleton pregnancy at a gestational age of 36 wks or more with a medical or
obstetric indication for induction
- Both nulliparous and multiparous women
- A cephalic presentation
- An unfavorable cervix (Bishop's score less than 8)
- A reassuring fetal heart tracing.
Exclusion Criteria:
- Rupture of membranes
- Multiple gestation
- Malpresentation (presentation other than cephalic)
- Previous cesarean delivery
- Known contraindications to the use of prostaglandins (e. g. asthma)
- Grandmultiparity (more than 5)
- Significant fetal or maternal concerns that made induction necessary under continuous
monitoring (e. g. severe IUGR, severe preeclampsia)
Locations and Contacts
American University of Beirut Medical Center, Beirut, Lebanon
Additional Information
Starting date: January 2004
Last updated: July 12, 2012
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