Induction of LabourPhase 3NCT03489928
Misoprostol Labour Induction Study
A Phase 3 study testing Oral Misoprostol, Vaginal Misoprostol and Dinoprostone in people with Induction of Labour and Labour, Induced, run by David Young.
Trial 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. Read more about this study
- Who is it for?
- Any age, women onlyHealthy volunteers can take part
- Conditions the study is for
- Induction of Labour, Labour, Induced
- What is being tested?
- Oral Misoprostol, Vaginal Misoprostol and Dinoprostone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 511 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 1999to 1 Dec 2000
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: A Randomized Controlled Trial of Oral Misoprostol, Low Dose Vaginal Misoprostol and Vaginal Dinoprostone for Induction of Labour
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.
Read the 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
- Being tested
- Oral Misoprostol, Vaginal Misoprostol, Dinoprostone
- Keywords
- Labour, Induction, Misoprostol, Dinoprostone, Oxytocin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral MisoprostolDrug
Also called Oral Cytotec
Prostaglandin E1 - 100ug tablet, divided in half by pharmacy staff to be administered by mouth.
Vaginal MisoprostolDrug
Also called Vaginal Cytotec
Prostaglandin E1 - 100ug oral tablet, divided in quarters by pharmacy staff, vaginal placement of one or two quarters as needed every 6 hours
DinoprostoneDrug
Also called Prostin
Prostaglandin E2 - 1-2mg gel manufactured for vaginal use; placed vaginally every 6 hours as needed.
| Study group | Role | What they receive |
|---|---|---|
| Oral Misoprostol | Experimental | 50ug po q4h orally, as needed Receives: Drug: Oral Misoprostol |
| Low dose vaginal misoprostol | Experimental | 25-50ug q6h, vaginally, as needed Receives: Drug: Vaginal Misoprostol |
| Usual vaginal dinoprostone | Experimental | 1-2mg q6h, vaginally as needed Receives: Drug: Dinoprostone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time interval from induction (at randomization) to vaginal birth
The chosen clinically important difference: 4 hours (240 minutes) difference. Caesarean sections could not be included in this planned parametric analysis (ANOVA) comparison of means
Measured: Randomization to newborn vaginal birth, assessed through to study completion, up to 10 weeks
Secondary outcomes (15)
Time interval from induction (at randomization) to birth
Rank order nonparametric analysis [Kruskal Wallis (KW)] where a Caesarean is a failure to deliver vaginally and ranked longer than any vaginal birth- comparison of medians (KW ANOVA).
Measured: Randomization to newborn birth, assessed through to study completion, up to 10 weeks
Profound newborn acidemia
Frequency of newborns with umbilical cord blood arterial pH < 7.0
Measured: Cord blood gas sample collected at birth
Newborn respiratory depression
Frequency of newborns with Apgar score at 5 minutes < 4
Measured: Assessed at 5 minutes after birth
Newborn birth asphyxia
Frequency of participants whose newborn experiences birth asphyxia as defined in the American College of Obstetrics and Gynecology Committee Opinion # 197 (Int J Gynecol Obstet 1998;61:309-10). The newborn with birth asphyxia must have each of the following four criteria :[1] profound academia (umbilical cord blood arterial pH< 7.0, obtained at birth); and (2) Apgar score <4 at five minutes as assessed by neonatal caregivers; and [3] neonatal neurologic sequelae (newborn with one or more of seizures, hypotonia, coma);and [4] dysfunction in one or more of the cardiovascular, gastrointestinal, hematologic, pulmonary, hepatic or renal systems. Criteria (3) and (4) are as assessed by neonatal caregivers from birth to newborn hospital discharge.
Measured: Birth to newborn hospital discharge, assessed up to 10 weeks
Newborn severe metabolic acidemia
Frequency of newborns with umbilical cord arterial blood base deficit >16.0 mmol/L
Measured: Cord blood gas sample collected at birth
Newborn moderate metabolic acidemia
Frequency of newborns with umbilical cord arterial blood base deficit >12.0 mmol/L
Measured: Cord blood gas sample collected at birth
Birth method
Frequency of spontaneous, operative vaginal (vacuum and/or forceps), or caesarean birth
Measured: At newborn birth
Oxytocin Use
Frequency of participants who received intrapartum use of oxytocin for labor augmentation or induction
Measured: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Epidural Use
Frequency of participants who received an epidural for intrapartum analgesia
Measured: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Perineal Trauma
Frequency of participants who had received suture perineal repair of a laceration or episiotomy
Measured: Randomization to maternal hospital discharge, assessed up to 10 weeks
Caesarean Section
Frequency of Caesarean section
Measured: At newborn birth
Maternal nausea
Frequency of participants who had nausea during labor
Measured: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Maternal vomiting
Frequency of participants who had vomiting during labor
Measured: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Maternal diarrhea
Frequency of participants experiencing diarrhea during labor
Measured: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Excessive uterine activity
Frequency of tachysystole and/or hyperstimulation - blind review of fetal heart rate, uterine contraction tracings by research team physician, remote from delivery.
Measured: Randomization to birth, assessed through to study completion, up to 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2018
- Study start1 Apr 1999
- Primary completion1 Dec 2000
- Study completion1 Dec 2000
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Induction of LabourStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomly assigned to one of three approaches to initiation of labour induction. Study group allocation will be stratified based on membrane status (ruptured/intact). Sequentially numbered opaque envelopes contain group assignment prepared using computer generated random number tables, in blocks of 4 and 6. Group 1 will receive misoprostol 50µgs, repeated at 4hr intervals until one of the following occurs: progressive labour, contraction frequency of 3 per 10 minutes, non-reassuring fetal heart rate tracing, or delivery. Group 2 will receive misoprostol 25µg initial dose and then 25-50µg placed in the vagina at 6hr intervals to the same effect. Group 3 will have induction of labour managed by the usual method here at the IWK (intravaginal or intracervical prostaglandin gel and IV oxytocin drip). All care decisions will be made by the attending physician. The patient will be reassessed before each administration of misoprostol.
- Masking
- None (open label)
- Enrolment
- 511 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Young
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Young, IWK Health Centre
- Investigators
- David C Young, MD MSc FRCSC, Principal investigator, IWK Health CentreB A Armson, MD MSc FRCSC, Study director, IWK Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03489928
- Sponsor's protocol ID
- REB#1415
- Other IDs
- 051.731.7303088
- Status last verified
- Apr 2018
- First submitted
- 6 Mar 2018
- Last updated
- 6 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: no sharing plan is in place
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of Oral Misoprostol, Low Dose Vaginal Misoprostol and Vaginal Dinoprostone for Induction of Labour
- ClinicalTrials.gov ID
- NCT03489928
- Acronym / sponsor ID
- REB#1415
- Conditions
- Induction of Labour, Labour, Induced
- Keywords
- Labour, Induction, Misoprostol, Dinoprostone, Oxytocin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 511 participants (actual)
- Lead sponsor
- David YoungUniversity, hospital or other
- Study start
- 1 Apr 1999 (actual)
- Primary completion
- 1 Dec 2000 (actual)
- Study completion
- 1 Dec 2000 (actual)
- First posted
- 6 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)].
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients will be randomly assigned to one of three approaches to initiation of labour induction. Study group allocation will be stratified based on membrane status (ruptured/intact). Sequentially numbered opaque envelopes contain group assignment prepared using computer generated random number tables, in blocks of 4 and 6. Group 1 will receive misoprostol 50µgs, repeated at 4hr intervals until one of the following occurs: progressive labour, contraction frequency of 3 per 10 minutes, non-reassuring fetal heart rate tracing, or delivery. Group 2 will receive misoprostol 25µg initial dose and then 25-50µg placed in the vagina at 6hr intervals to the same effect. Group 3 will have induction of labour managed by the usual method here at the IWK (intravaginal or intracervical prostaglandin gel and IV oxytocin drip). All care decisions will be made by the attending physician. The patient will be reassessed before each administration of misoprostol.
| Arm | Type | Receives |
|---|---|---|
| Oral Misoprostol | Experimental | Drug: Oral Misoprostol50ug po q4h orally, as needed |
| Low dose vaginal misoprostol | Experimental | Drug: Vaginal Misoprostol25-50ug q6h, vaginally, as needed |
| Usual vaginal dinoprostone | Experimental | Drug: Dinoprostone1-2mg q6h, vaginally as needed |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral MisoprostolAlso: Oral CytotecProstaglandin E1 - 100ug tablet, divided in half by pharmacy staff to be administered by mouth. | Drug | Oral Misoprostol |
| Vaginal MisoprostolAlso: Vaginal CytotecProstaglandin E1 - 100ug oral tablet, divided in quarters by pharmacy staff, vaginal placement of one or two quarters as needed every 6 hours | Drug | Low dose vaginal misoprostol |
| DinoprostoneAlso: ProstinProstaglandin E2 - 1-2mg gel manufactured for vaginal use; placed vaginally every 6 hours as needed. | Drug | Usual vaginal dinoprostone |
Primary outcome
Time interval from induction (at randomization) to vaginal birth
Time frame: Randomization to newborn vaginal birth, assessed through to study completion, up to 10 weeks
The chosen clinically important difference: 4 hours (240 minutes) difference. Caesarean sections could not be included in this planned parametric analysis (ANOVA) comparison of means
15 secondary outcomes
Time interval from induction (at randomization) to birth
Time frame: Randomization to newborn birth, assessed through to study completion, up to 10 weeks
Profound newborn acidemia
Time frame: Cord blood gas sample collected at birth
Newborn respiratory depression
Time frame: Assessed at 5 minutes after birth
Newborn birth asphyxia
Time frame: Birth to newborn hospital discharge, assessed up to 10 weeks
Newborn severe metabolic acidemia
Time frame: Cord blood gas sample collected at birth
Newborn moderate metabolic acidemia
Time frame: Cord blood gas sample collected at birth
Birth method
Time frame: At newborn birth
Oxytocin Use
Time frame: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Epidural Use
Time frame: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Perineal Trauma
Time frame: Randomization to maternal hospital discharge, assessed up to 10 weeks
Caesarean Section
Time frame: At newborn birth
Maternal nausea
Time frame: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Maternal vomiting
Time frame: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Maternal diarrhea
Time frame: Randomization to maternal delivery, assessed through to study completion, up to 10 weeks
Excessive uterine activity
Time frame: Randomization to birth, assessed through to study completion, up to 10 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2018.
- Individual participant dataSharing planned: No. no sharing plan is in place
Related trials for Induction of Labour
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Gestational Diabetes Mellitus (GDM)
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Prediction of Intrapartum Fetal Compromise After Elective Induction of Labour
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Comparative Analysis of Labor Induction Using a Balloon Catheter at Home Versus in the Hospital
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The Ophthalmic Artery Doppler Evaluation Prior to Labor Induction and Adverse Intrapartum Fetal Outcomes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David C Young, MD MSc FRCSC principal investigator
IWK Health Centre
B A Armson, MD MSc FRCSC study director
IWK Health Centre
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oral Misoprostol, Vaginal Misoprostol and Dinoprostone in people with Induction of Labour and Labour, Induced, run by David Young.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time interval from induction (at randomization) to vaginal birth (time frame: Randomization to newborn vaginal birth, assessed through to study completion, up to 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.