Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000522415
Ethics application status
Approved
Date submitted
19/04/2016
Date registered
21/04/2016
Date last updated
5/06/2019
Date data sharing statement initially provided
5/06/2019
Date results information initially provided
5/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cervical Ripening Using Misoprostol vs Dinoprostone: A randomised, triple-blinded, interventional study comparing safety and efficacy in primiparous women
Scientific title
Cervical Ripening Using Misoprostol vs Dinoprostone: A randomised, triple-blinded, interventional study comparing safety and efficacy in primiparous women
Secondary ID [1] 289040 0
Nil Known
Universal Trial Number (UTN)
U1111-1182-0920
Trial acronym
CRUMD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Ripening 298457 0
Induction of Labour 298458 0
Condition category
Condition code
Reproductive Health and Childbirth 298558 298558 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Misoprostol 200microgram slow release pessary is placed per vagina on admission to hospital. This occurs 48 hours prior to planned induction of labour. The cervix is reassessed 24 hours post administration and misoprostol pessary removed unless indicated earlier. (indications for early removal include active labour, ruptured membranes, abnormal fetal cardiotocography, uterine hyperstimulation)
Intervention code [1] 294523 0
Treatment: Drugs
Comparator / control treatment
Dinoprostone 10mg slow release pessary is placed per vagina on admission to hospital. This occurs 2 days prior to planned induction of labour. The cervix is reassessed 24 hours post administration and dinoprostone pessary removed unless indicated earlier. (indications for early removal include active labour, ruptured membranes, abnormal fetal cardiotocography, uterine hyperstimulation)
Control group
Active

Outcomes
Primary outcome [1] 298041 0
Number of women requiring further cervical ripening with cervical ripening balloon following treatment as assessed by Bishops' Score less than or equal to 7 following removal of treatment drug
Timepoint [1] 298041 0
24 hours post insertion of treatment
Primary outcome [2] 298042 0
Number of women requiring induction of labour with oxytocin as assessed by the number of women who have not achieved spontaneous labour following treatment
Timepoint [2] 298042 0
48 hours post treatment
Primary outcome [3] 298043 0
Number of women requiring intervention for uterine hyperstimulation that is assessed by the number of women having 6 or more contractions in 10 minutes who require tocolysis or other intervention for fetal cardiotocography changes
Timepoint [3] 298043 0
within 24 hours of treatment
Secondary outcome [1] 322998 0
Number of women requiring delivery by caesarean section as determined by review of medical record
Timepoint [1] 322998 0
within 4 days of treatment
Secondary outcome [2] 322999 0
Time gap from treatment to vaginal delivery as assessed by review of medical record
Timepoint [2] 322999 0
within 4 days of treatment
Secondary outcome [3] 323000 0
Neonatal morbidity or mortality as assessed by presence of hypoxic ischaemic encephalopathy, 5 minute apgar score <7, Neonatal Intensive Care admission
Timepoint [3] 323000 0
within 24 hours of birth

Eligibility
Key inclusion criteria
1) Pregnant women between 37+0 and 41+4 weeks gestation
2) Having first baby
3) Induction of labour deemed medically indicated
4) Bishops score less than or equal to 4
5) age >=18
6) BMI <50 at booking visit
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Active labour
2) Ruptured membranes
3) Non-cephalic presentation
4) Previous caesarean section or other uterine surgery
5) Unexplained vaginal bleeding >24 weeks gestation
6) Suspected or known chorioamnionitis
7) Suspected or known fetal compromise (abnormal antenatal fetal heart rate pattern, ultrasound showing fetal growth <10th centile, oligohydramnios, polyhydramnios, abnormal dopplers)
8) Unable to read or speak English without the aid of an interpreter

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Vaginal pessaries identical in appearance
Sealed unidentified packaging
Numbered packaging
Randomisation conducted by 3rd party external to study
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random allocation sequence
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
There will be 200 women per arm, 400 total population

Misoprostol has been compared to dinoprostone in a phase III trial called the EXPIDITE study.

Based on the number of primiparous births we have at John Hunter Hospital, to replicate Wing et al with a 26% reduction in the use of oxytocin with a power of 90% and a p value <0.05 we would need 72 women per arm

In order to reduce the rate of CRB use at John Hunter Hospital from 28% to 14% with a power of 90% and p value <0.05 we would need 173 women per arm.

To replicate the difference in tachysystole rates of 13% and 4% with a 90% power and a p value <0.05 we will need 200 women per arm

5 of the 6 endpoints of this trial are dichotomous variables and so the chi-square test will be used to test for differences between groups
Time to vaginal delivery will be tested using Cox Proportional Hazards Regression

Wing D, Brown R, Plante L, Miller H, Rugarn O, Powers B; Misoprostol Vaginal Insert and Time to Vaginal Delivery (Obstet Gynecol 2013;122:201–9)

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Misoprostol vaginal insert withdrawn from market world wide by Ferring Pharmaceuticals. TGA approval withdrawn 30.04.2019
Date of first participant enrolment
Anticipated
Actual
13/10/2015
Date of last participant enrolment
Anticipated
20/12/2019
Actual
14/04/2019
Date of last data collection
Anticipated
28/06/2019
Actual
Sample size
Target
400
Accrual to date
Final
208
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5637 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment postcode(s) [1] 13095 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 293411 0
Hospital
Name [1] 293411 0
John Hunter Hospital
Country [1] 293411 0
Australia
Funding source category [2] 293412 0
Commercial sector/Industry
Name [2] 293412 0
Ferring Pharmaceuticals PTY Ltd
Country [2] 293412 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Lookout Rd
New Lambton Heights
NSW 2305
Country
Australia
Secondary sponsor category [1] 292238 0
None
Name [1] 292238 0
Address [1] 292238 0
Country [1] 292238 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294860 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 294860 0
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 294860 0
Australia
Date submitted for ethics approval [1] 294860 0
30/04/2015
Approval date [1] 294860 0
02/06/2015
Ethics approval number [1] 294860 0
15/05/20/3.03

Summary
Brief summary
Misoprostol and Dinoprostone are both medications used to ripen a woman's cervix in preparation for labour.
In a phase III trial by Wing et al misoprostol vaginal insert, when compared to dinoprostone vaginal insert, was thought to reduce the time from insert to vaginal delivery and decrease the number of women needing further intervention by oxytocin for induction of labour by 26% without an increase in the complications of caesarean section or neonatal morbidity. Misoprostol was found to increase the rate of tachysystole (too frequent uterine contractions) to 13% compared with 4% for dinoprostone. Wing et al used both primiparous women and multiparous women in their study.
We hypothesize that by using misoprostol in primiparous women only we may still be able to achieve the significant reduction in need for other interventions for induction of labour but without the significant increase in rates of uterine tachysystole.

Women admitted to the study will have either the misoprostol or dinoprostone inserted for cervical ripening and data collected on whether or not they then needed to have a cervical ripening balloon for further ripening, whether they needed oxytocin for induction of labour, whether they had too many contractions that required intervention to control, what their mode of delivery was, what the time interval between when the pessary was inserted and when they delivered and whether or not there were any neonatal complications.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 65262 0
Dr Angela Boulton
Address 65262 0
John Hunter Hospital
Lookout Rd
New Lambton Heights
NSW 2305
Country 65262 0
Australia
Phone 65262 0
+61 2 4921 4385
Fax 65262 0
Email 65262 0
Angela.Boulton@hnehealth.nsw.gov.au
Contact person for public queries
Name 65263 0
Dr Angela Boulton
Address 65263 0
John Hunter Hospital
Lookout Rd
New Lambton Heights
NSW 2305
Country 65263 0
Australia
Phone 65263 0
+61 2 4921 4385
Fax 65263 0
Email 65263 0
Angela.Boulton@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 65264 0
Dr Gracia Chong
Address 65264 0
John Hunter Hospital
Lookout Rd
New Lambton Heights
NSW 2305
Country 65264 0
Australia
Phone 65264 0
+61 2 4921 4385
Fax 65264 0
Email 65264 0
Gracia.Chong@hnehealth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
de-identified individual participant data underlying published trial results
When will data be available (start and end dates)?
immediately following publication to no end date determined
Available to whom?
Ferring pharmaceuticals as per funding agreement. It will also be made available to researchers on a case-by-case basis who provide a methodologically sound proposal
Available for what types of analyses?
meta-analyses
How or where can data be obtained?
access subject to approvals by principal investigator


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2199Clinical study report    This will be available when completed



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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