A Randomized Trial of Oral Misoprostol Alone Versus Oral Misoprostol Followed by Oxytocin for Labour Induction (MOLI)

A Randomized Trial Comparing Oral Misoprostol Alone with Oral Misoprostol Followed by Oxytocin in Women Induced for Hypertension of Pregnancy

The primary objective of the trial is to assess the following: In women who have undergone cervical preparation with oral misoprostol as part of labour induction for hypertensive disease in India, is augmentation using oral misoprostol superior to the standard protocol of intravenous oxytocin?

Study Overview

• Status: Completed
• Conditions: Induction of Labor
• Intervention / Treatment: Drug: Oxytocin; Drug: Oral misoprostol

Detailed Description

Every year approximately 30 000 women die from hypertensive disease in pregnancy. Magnesium sulphate and anti-hypertensives reduce morbidity, but delivery is the only cure. Low dose oral misoprostol, a prostaglandin E1 analogue, is a highly effective method for labour induction. Usually, once active labour has commenced, the misoprostol is replaced with an intravenous oxytocin infusion. However, some studies have shown that oral misoprostol can be continued into active labour. In the Cochrane review on labour induction, those whose augmentation was continued with misoprostol (M/M protocol) had 42% less CSs than those who changed to oxytocin (M/Ox protocol; 15% vs 26%). This misoprostol-only protocol would be simpler and probably more acceptable to women. However, these two protocols have never been directly compared. We propose a pragmatic, open-label, randomised trial to compare an M/M labour induction protocol with the standard M/Ox protocol.

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Nagpur, India
    • Government Medical College (GMC)
  • Maharashtra
    • Nagpur, Maharashtra, India
      • Daga Memorial Women's Hospital
    • Sevagram, Maharashtra, India
      • Mahatma Gandhi Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• • Ongoing pregnancies with a live fetus who require induction because of preeclampsia or hypertensionWomen will be included irrespective of whether an intrapartum caesarean birth on fetal grounds would be considered or not

  • Women age ≥18 years
  • Signed informed consent form
  • Undergone cervical ripening with misoprostol if cervix initially unfavourable
  • Decision to augment labour for inadequate uterine contractions despite ruptured membranes (either artificial or spontaneous as part of the induction process)s

Exclusion Criteria:

• Women with previous caesarean births
• Those unable to give informed consent
• Cervical ripening with agents other than misoprostol (e.g. Foley catheter, prostaglandins)
• Multiple pregnancy
• History of allergy to misoprostol
• Adequate uterine activity
• Pre- induction Ruptured amniotic membranes
• Frank chorioamnionitis (systemic illness with purulent vaginal discharge and uterine tenderness)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Oxytocin infusion; Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.; The oxytocin group will not receive misoprostol after the membranes have ruptured.	Drug: Oxytocin; Oxytocin infusion will be given through an electronic infusion pump. One unit of oxytocin will be injected in 500 mL of Ringer's lactate, started at a rate of 2 mU/min, and increased every 30 min by 2 mU/min until there are three to four contractions every 10 min. The rate will be titrated to maintain that contraction frequency. The maximum dose will be 20mU/min as oxytocin summary product characteristics.; The oxytocin group will not receive misoprostol after the membranes have ruptured.; Other Names: Pitocin
Other: Oral misoprostol; An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).; The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes); If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted; In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.	Drug: Oral misoprostol; An initial dose of misoprostol 25mcg will be given orally after randomisation (this must be a minimum of 2 hours after the previous misoprostol dose).; The next dose of oral misoprostol will be omitted if moderate or strong contractions are occurring at 3 in 10 minutes or more (i.e. 9 or more in the preceding 30 minutes); If contractions subsequently reduce to less than 3 in 10 (under 9 in 30 minutes), or become irregular or mild, then the oral misoprostol 25mcg can be restarted; In the event of inadequate progress, clinicians will be advised to give further misoprostol if there are any concerns about contractions strength or frequency.; Other Names: Misoprost

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Caesarean birth	Rate of caesarean birth in the treatment arm	At delivery

Collaborators and Investigators

• Sponsor: University of Liverpool
• Collaborators: Gynuity Health Projects; Daga Memorial Women's Hospital, Nagpur, India; Government Medical College, Nagpur; Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, India
• Investigators: Principal Investigator: Andrew D Weeks, FRCOG, University of Liverpool

Publications and helpful links

General Publications

• Bracken H, Lightly K, Mundle S, Kerr R, Faragher B, Easterling T, Leigh S, Turner M, Alfirevic Z, Winikoff B, Weeks A. Oral Misoprostol alone versus oral misoprostol followed by oxytocin for labour induction in women with hypertension in pregnancy (MOLI): protocol for a randomised controlled trial. BMC Pregnancy Childbirth. 2021 Jul 29;21(1):537. doi: 10.1186/s12884-021-04009-8.

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Actual): July 30, 2022
• Study Completion (Actual): July 30, 2022

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: oxytocin; misoprostol; preeclampsia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Gastrointestinal Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Oxytocics; Anti-Ulcer Agents; Oxytocin; Misoprostol
• Other Study ID Numbers: 4007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data from this study will be confidential until the database is closed at the end of the study. Following this the study investigators will have exclusive access to the data until the publication of the results in a journal. Once this has happened, the database will be open to other researchers upon request. Open access databases will also be sought so as to maximise the availability of our research data with as few restrictions as possible, in line with MRC and Wellcome Trust policy. The consent form will include a clause for the woman to give permission for her anonymous data to be used for future research studies.
• IPD Sharing Time Frame: The data will be released upon publication of the trial results. After this, the data will be shared on a public database to maximise the viability of the data.
• IPD Sharing Access Criteria: Initially this will be upon request with later public publication of the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No