MISOBEST - Orally Misoprostol Solution (Cytotec®) Versus Orally Misoprostol as a Tablet (Angusta®) for Induction of Labor
Condition: Induced Vaginal Delivery
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of the study is to evaluate efficacy of the cervical ripening of misoprostol
      administration in oral tablet, Angusta® compared with the off-label solution of misoprostol
      (Cytotec®) for induction of labor (IOL). Since there is a large cost difference between the
      preparations (Angusta® is 43 times more expensive than Cytotec®) it is, from a socio-economic
      perspective, of great interest to evaluate if Angusta can be replaced by Cytotec.
    

Detailed description: 
      In Sweden as in most other countries, the rate of induction of labor (IOL) has steadily
      increased, peaking at 27% of all deliveries in 2020. Due to recently published studies
      showing decreased perinatal mortality with IOL at 41 instead of 42 gestational weeks,
      national guidelines have changed to offering all pregnant women reaching 41 weeks IOL, which
      will increase induction rates and subsequent cost of IOL for medication further.

      Spontaneous onset of labor is usually preferred, as it generally means lower risk of
      complications compared to IOL. If delivery needs to be induced in women with an unfavorable
      cervical status, an oral solution of misoprostol is a safe and inexpensive method that is
      easy to control and provides a high success rate of vaginal deliveries with a very low risk
      of hyper stimulation. Since the preparation of misoprostol (Cytotec®) has been used off-label
      with the solution being prepared locally at every unit, the profession has been looking for
      alternatives. Angusta® 25 ug tablets is the alternative that has been developed and approved
      but without being compared to the oral solution of misoprostol, the most commonly used method
      for IOL in Sweden. In addition, Angusta® is 43 times more expensive (1011 SEK compared to
      23.60 SEK for Cytotec® for eight doses) considering "a typical induction" for primiparous
      women. Both methods are currently in use in clinical practice in Sweden.

      A recent study conducted in Sweden 2020 shows that the Area Under the Curve (AUC) for the
      concentration in the blood of misoprostol after administration of 25 ug Cytotec® po compared
      to Angusta® 25ug po differs . The AUC is 32.9% higher with Cytotec® compared to Angusta®. The
      lower AUC for Angusta® may result in lower efficacy and time to delivery. However, this is
      unknown. The reason for this difference may be that a greater proportion of misoprostol is
      absorbed buccally and/or sublingually with use of misoprostol as a solution compared to when
      it is used as a tablet. Misoprostol has significantly different effect on uterine
      contractility depending on method of administration(1). Thus, using Angusta® may result in
      negative health economic outcomes due to higher price and in addition, a longer time spent in
      the delivery unit. No comparison of these two formulations has been performed in clinical
      practice.
    

Intervention name(s): Misoprostol
Intervention type(s): Drug
Intervention description(s): Women presenting at the study site with an indication for IOL will receive written and oral information about the study. They will have the opportunity to ask questions. If the woman agrees to participate and is deemed eligible, she will sign informed consent. The Swedish national guidelines regarding the method of IOL will be followed. Women will have an abdominal palpation to exclude malpresentation, a CTG, and a digital cervical exam to establish bishop score (BS) prior to inclusion (as per clinical practice). Randomization will be performed by the attending physician, midwife or study coordinator. Randomization will be by opening numbered opaque sealed envelopes in sequential order containing the randomization code. There are no restrictions for use of other medications. All concomitant medication will be recorded in the CRF.
Intervention MeSH terms: Misoprostol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment