MISOBEST - Orally Misoprostol Solution (Cytotec®) Versus Orally Misoprostol as a Tablet (Angusta®) for Induction of Labor

Karolinska Institute

Status and phase: Completed; Phase 3

Conditions: Induced Vaginal Delivery

Treatments: Drug: Misoprostol

Study type: Interventional

Funder types: Other

Identifiers

NCT05424445

EudraCT 2020-000663-23

Details and patient eligibility

About

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.

Full 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.

Enrollment: 884 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Singleton gestations
• Cephalic presentation
• ≥37-42+0 weeks of gestation
• Unfavorable cervix score BS <6 in nulliparous women and <5 in parous women
• All participating women in the studies will receive oral and written information and must give informed consent before participation

Exclusion criteria

1. Inability to understand the study information written in Swedish or English
2. Previous hysterotomy (scar in the uterine myometrium)
3. Non-reassuring cardiotocography (CTG) on admission (the door-test, first 20 minutes of registration of CTG).
4. Hypersensitivity to the active substance
5. If active labor has started
6. When oxytocin infusion is already used
7. Placenta previa
8. Renal failure (GFR <15 ml/min/1.73 m2).
9. Any condition or circumstance due to which the investigator considers it is not in the best interest of subject to participate in the study or the inclusion of a subject risks negatively impacting the scientific or ethical integrity of the clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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884 participants in 2 patient groups

Cytotec®

Experimental group

Description:

IOL with misoprostol oral solution (Cytotec®) 25 ug every second hour, up to eight doses, or until painful contractions are obtained. Thereafter IOL will proceed according to clinical practice.

Treatment:

Drug: Misoprostol

Angusta®

Active Comparator group

Description:

IOL with misoprostol oral tablets (Angusta®) 25 ug every second hour, up to eight doses, or until painful contractions are obtained. Thereafter IOL will proceed according to clinical practice.

Treatment:

Drug: Misoprostol