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

NCT05424445 | Completed Phase 3

• 1 other identifier: EudraCT 2020-000663-23
• Study Type: interventional
• Target: 884
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Induced Vaginal Delivery

Outcome Measures

Primary Outcomes (1)

• Vaginal delivery within 24 hours (VD 24) rate as difference in proportions in each group according to intention-to-treat (ITT), and per protocol.

  VD24 - (yes/no) is a dichotomous variable extracted from medical records.

  Time point for extraction of data: immediately after the intervention/procedure/surgery

Secondary Outcomes (7)

• Proportion of vaginal deliveries (VD) in total.

  Time point for extraction of data: immediately after the intervention/procedure/surgery.

• The induction-to-vaginal delivery time.

  Time point for extraction of data:immediately after the intervention/procedure/surgery.

• The mean number of doses of each preparation.

  Time point for extraction of data: immediately after the intervention/procedure/surgery.

• The proportion of neonates with Apgar <7 at 5 minutes.

  Time point for extraction of data: immediately after the intervention/procedure/surgery.

• Postpartum bleeding (PPH) >1000 ml.

  Time point for extraction of data: immediately after the intervention/procedure/surgery.

Study Arms (2)

Cytotec®

EXPERIMENTAL

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.

Drug: Misoprostol

Angusta®

ACTIVE COMPARATOR

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.

Drug: Misoprostol

Interventions

Misoprostol DRUG

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.

Angusta®; Cytotec®

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Inability to understand the study information written in Swedish or English
• Previous hysterotomy (scar in the uterine myometrium)
• Non-reassuring cardiotocography (CTG) on admission (the door-test, first 20 minutes of registration of CTG).
• Hypersensitivity to the active substance
• If active labor has started
• When oxytocin infusion is already used
• Placenta previa
• Renal failure (GFR \<15 ml/min/1.73 m2).

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Södersjukhuset

Stockholm, 118 83, Sweden

Location

Related Publications (5)

• Stephansson O, Petersson K, Bjork C, Conner P, Wikstrom AK. The Swedish Pregnancy Register - for quality of care improvement and research. Acta Obstet Gynecol Scand. 2018 Apr;97(4):466-476. doi: 10.1111/aogs.13266. Epub 2017 Dec 14.

  PMID: 29172245 BACKGROUND

• Wennerholm UB, Saltvedt S, Wessberg A, Alkmark M, Bergh C, Wendel SB, Fadl H, Jonsson M, Ladfors L, Sengpiel V, Wesstrom J, Wennergren G, Wikstrom AK, Elden H, Stephansson O, Hagberg H. Induction of labour at 41 weeks versus expectant management and induction of labour at 42 weeks (SWEdish Post-term Induction Study, SWEPIS): multicentre, open label, randomised, superiority trial. BMJ. 2019 Nov 20;367:l6131. doi: 10.1136/bmj.l6131.

  PMID: 31748223 BACKGROUND

• Tang J, Kapp N, Dragoman M, de Souza JP. WHO recommendations for misoprostol use for obstetric and gynecologic indications. Int J Gynaecol Obstet. 2013 May;121(2):186-9. doi: 10.1016/j.ijgo.2012.12.009. Epub 2013 Feb 19.

  PMID: 23433680 BACKGROUND

• Amini M, Reis M, Wide-Swensson D. A Relative Bioavailability Study of Two Misoprostol Formulations Following a Single Oral or Sublingual Administration. Front Pharmacol. 2020 Feb 12;11:50. doi: 10.3389/fphar.2020.00050. eCollection 2020.

  PMID: 32116725 BACKGROUND

• Svensk E, Bessfelt E, Brismar Wendel S, Kopp Kallner H, Wallstrom T. Misoprostol as Oral Solution or Oral Tablet for Induction of Labour (MISOBEST): A Randomised Controlled Non-Inferiority Trial. BJOG. 2025 Feb;132(3):288-296. doi: 10.1111/1471-0528.17986. Epub 2024 Oct 23.

  PMID: 39440409 DERIVED

MeSH Terms

Interventions

Misoprostol

Intervention Hierarchy (Ancestors)

Prostaglandins E, Synthetic; Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Due to the nature of the study, comparing the same drug but in different preparations, blinding is not deemed feasible.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, senior consultant

Study Record Dates

• First Submitted: January 21, 2022
• First Posted: June 21, 2022
• Study Start: January 21, 2022
• Primary Completion: December 31, 2022
• Study Completion: May 21, 2023
• Last Updated: August 18, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)