Misoprostol Labour Induction Study

NCT ID: NCT03489928

Last Updated: 2018-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 511 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-04-01
• Study Completion Date: 2000-12-01

Brief Summary

Labour induction is a frequent obstetric intervention (~20%). Prostaglandins (PGs) are effective agents, but gastrointestinal (GI) intolerance has limited use to non-oral routes. The traditional oxytocin "drip" requires intravenous (IV) use and discourages mobility. Misoprostol, a PG analogue, is marketed for oral treatment of GI disorders, but initiates uterine contraction, an undesirable GI side effect. Recently, there has been a research "boom" on vaginal misoprostol use in pregnancy to induce term labour drawing on this "side effect:". The principal investigator has led one of three groups worldwide which has published on oral misoprostol to study effectiveness, GI tolerance, and safety for mother/baby in term labour induction. Cost per patient has been less then one percent that of other PGs, even less than IV oxytocin.

Detailed Description

Labour induction is a frequent obstetric intervention (20-30%). Prostaglandins (PGs) are effective agents, but gastrointestinal (GI) intolerance has limited use to intracervical and vaginal administration of PGE2 gels. Misoprostol, a prostaglandin E2 (PGE1) analogue, is marketed for oral treatment of upper GI disorders. The past five years has seen mushrooming literature on its use to initiate uterine contractions for pregnancy termination in the first and second trimesters, and labour induction in the third. Vaginal administration has been used almost exclusively, has been cost effective (less than one percent the cost of PGE2) and without demonstrated harm to mother or newborn. The investigators have published a randomized control trial (RCT) on vaginal use, and have also published a 275 subject RCT of oral misoprostol versus a traditional induction regime of (physician chosen combinations of intracervical or vaginal dinoprostone, intravenous (IV) oxytocin and artificial membrane rupture). Oral misoprostol was effective, well tolerated and without harm to mother or newborn. The investigators have in press a double blind RCT or oral versus vaginal misoprostol in 206 subjects. Oral misoprostol was effective, though time to vaginal birth was 226 min longer, due to more time before labour was initiated. Oral misoprostol was associated with less uterine hyperstimulation (P<0.04). The investigators have also completed an RCT of oral misoprostol versus IV oxytocin with term pre-labour membrane rupture. Again, effectiveness was shown. There is no larger published collective experience with oral misoprostol labour induction. Before embarking on a costly RCT to evaluate more substantive outcomes (Caesareans or neonatal asphyxia) with sample size greater than 10,000, funding has been received for this three-group RCT of labour induction at term: oral misoprostol, vaginal misoprostol, and our centre's established approach.

PRIMARY RESEARCH QUESTION When induction of labour at term is indicated, is there more than a four-hour difference in time to vaginal birth between vaginal misoprostol (25µg initial dose, followed by 25-50µg every six hours as needed), oral misoprostol (50µg every four hours as needed) and the Izaak Walton Killam (IWK) Health Centre established protocol? Secondary outcomes address harm to the newborn (including cord blood acid base analysis, and defined birth asphyxia criteria) and mother (Caesareans, peripartum interventions, maternal GI intolerance and excessive uterine activity).

RESEARCH PLAN Eligible subjects will be at gestations greater than 37 completed weeks, with a cephalic presenting live single fetus, who have an indication for induction, and no contraindication to induction, vaginal birth, or PG use. Random allocation will be blocked and stratified (on membrane status). Sample size calculations were based on: ∆=240 minutes, α(2 tailed) = 0.05, β=0.05, with a σ=588 minutes from the investigators' prior publications. Adjustments for anticipated Caesareans (<20%) were made. Sample size is 510. Recruitment within a year is supported by the group's prior research [more than 1000 inductions per year at IWK Grace ( the centre's name officially changed in November, 2000, to IWK Health Centre)].

Conditions

Induction of Labour; Labour, Induced

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Oral Misoprostol

50ug po q4h orally, as needed

Group Type: EXPERIMENTAL

Oral Misoprostol

Intervention Type: DRUG

Prostaglandin E1 - 100ug tablet, divided in half by pharmacy staff to be administered by mouth.

Low dose vaginal misoprostol

25-50ug q6h, vaginally, as needed

Group Type: EXPERIMENTAL

Vaginal Misoprostol

Intervention Type: DRUG

Prostaglandin E1 - 100ug oral tablet, divided in quarters by pharmacy staff, vaginal placement of one or two quarters as needed every 6 hours

Usual vaginal dinoprostone

1-2mg q6h, vaginally as needed

Group Type: EXPERIMENTAL

Dinoprostone

Intervention Type: DRUG

Prostaglandin E2 - 1-2mg gel manufactured for vaginal use; placed vaginally every 6 hours as needed.

Interventions

Oral Misoprostol

Prostaglandin E1 - 100ug tablet, divided in half by pharmacy staff to be administered by mouth.

Intervention Type: DRUG

Vaginal Misoprostol

Prostaglandin E1 - 100ug oral tablet, divided in quarters by pharmacy staff, vaginal placement of one or two quarters as needed every 6 hours

Intervention Type: DRUG

Dinoprostone

Prostaglandin E2 - 1-2mg gel manufactured for vaginal use; placed vaginally every 6 hours as needed.

Intervention Type: DRUG

Other Intervention Names

Oral Cytotec; Vaginal Cytotec; Prostin

Eligibility Criteria

Inclusion Criteria

• pregnant women
• gestational age 37 weeks or more based on ultrasound before 24 weeks
• live single fetus in cephalic presentation
• indication for induction of labour

Exclusion Criteria

• non reassuring fetal heart rate tracing
• maternal prior uterine surgery
• known hypersensitivity to misoprostol or other prostaglandin
• contraindication to vaginal birth
• fetal anomaly identified on antenatal ultrasound
• uncontrolled maternal asthma or epilepsy

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

David Young

OTHER

Sponsor Role: lead

Responsible Party

David Young

Active Staff Physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David C Young, MD MSc FRCSC

Role: PRINCIPAL_INVESTIGATOR

IWK Health Centre

B A Armson, MD MSc FRCSC

Role: STUDY_DIRECTOR

IWK Health Centre

Other Identifiers

051.731.7303088

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

REB#1415

Identifier Type: -

Identifier Source: org_study_id