Induction With Misoprostol: Oral Mucosa Versus Vaginal Epithelium (IMPROVE)
Condition: Pregnancy
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary objective of this study is to compare the efficacy and safety of vaginal and
      buccal misoprostol for women undergoing labor induction at greater than or equal to 37+ 0
      completed weeks gestation. Thus, the investigators have both efficacy and a safety primary
      outcomes.

      The secondary objective of this study is to assess the pharmacokinetic(PK) parameters with
      these two routes of administration in a sub-cohort of this trial. The long term objective of
      this line of research is to inform providers' clinical decision making for the large number
      of women having labor induction. By providing robust PK and pharmacodynamic (PD) evaluation,
      clinical outcomes data for these two routes of administration, clinicians will be informed
      for evidence-based decisions about the preferred route of administration of misoprostol.
    

Detailed description: 
      Misoprostol is currently administered in many different ways. It can be administered
      vaginally, rectally, orally, buccally, and sublingually. Each route has its benefits and
      potential drawbacks. While vaginal administration is most common, recent trends in practice
      have yielded more buccal use of this drug. There is extensive clinical experience with this
      agent and a large body of published reports supporting its safety and efficacy when used
      appropriately. However, we only found one published trial directly comparing buccal to
      vaginal misoprostol head-to-head. In that trial, there were no significant differences in any
      of the outcomes other than higher rates of tachysystole in the buccal group. However, this
      trial utilized higher doses of misoprostol (up to 100mcg) than are typically used clinically
      per the ACOG Practice Bulletin (starting at 25 mcg).

      Additionally, there are few comparisons of the pharmacokinetics of misoprostol between the
      buccal and vaginal routes. In fact, all of the PK studies comparing these routes are in women
      undergoing pregnancy terminations in the 1st or 2nd trimesters and do not include women
      undergoing labor induction at term. As the physiological changes in pregnancy have a profound
      impact on drug metabolism and disposition, this is an important gap in the current knowledge.

      The 3 Specific Aims of this trial are:

        1. To compare the efficacy and safety of 25 mcg of misoprostol initially followed by 50mcg
           thereafter administered by either buccal or vaginal route in a placebo-controlled,
           double blind RCT. We will recruit women at term undergoing labor induction to accomplish
           this trial.

        2. To compare the PK parameters of 25 mcg and 50 mcg of misoprostol administered by either
           buccal or vaginal routes. Further, we will analyze the clinical outcomes in Aim 1 based
           on the PK parameters, controlling for patient characteristics, to assess the impact of
           PK parameters on clinical success of this drug. In this way, we hope to comment on the
           strategic dose and individualized dosing model potential for labor induction with
           misoprostol.

        3. To compare the trial participant satisfaction with each route of administration to
           improve patient-based outcomes. This will be done by administering a satisfaction survey
           at the end of the trial. As participants will have study drug placed both buccally and
           vaginally, they will be uniquely able to comment on comfort and preference for route of
           delivery.

      We will recruit women who are admitted for term labor induction and for whom the provider
      plans to utilize misoprostol. Women will be randomized to receive either buccal or vaginal
      misoprostol; first dose will be 25 mcg followed by 50mcg for subsequent doses. Three hundred
      women will be recruited to the overall trial and a subcohort of 60 women will be recruited to
      participate in the PK portion of the trial.
    

Intervention name(s): misoprostol/placebo
Intervention type(s): Drug
Intervention description(s): buccal or vaginal routes of administration/ placebo to compare methods for efficacy and safety during induction.
Other intervention name(s): Cytotec
Intervention MeSH terms: Misoprostol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Diagnostic
Keywords: induction of labor; safety; pharmacokinetic; misoprostol