Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12612000884808
Ethics application status
Approved
Date submitted
23/07/2012
Date registered
20/08/2012
Date last updated
20/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Mifepristone and misoprostol compared with misoprostol alone for induction of labour of mid-trimester fetal demise
Scientific title
Among patients with a mid trimester fetal demise, does the use of mifepristone prior to misoprostol, compared with misoprostol alone, reduce the time to delivery?
Secondary ID [1] 260061 0
Nil known
Universal Trial Number (UTN)
U1111-1125-0671
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Management of second trimester fetal demise 265730 0
Mode of induction of labour 278921 0
Condition category
Condition code
Reproductive Health and Childbirth 265868 265868 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women allocated to the case group will receive 200mg oral mifepristone 24-48 hours prior to admission to hospital for standard protocol misoprostol interruption of pregnancy. Women will receive 400ug of vaginal misoprostol six hourly until delivery of the fetus.
Intervention code [1] 269501 0
Treatment: Drugs
Comparator / control treatment
Women allocated to the control group will receive a placebo orally 24-48 hours prior to admission to hospital for standard protocol misoprostol interruption of pregnancy. Women will receive 400ug of vaginal misoprostol six hourly until delivery of the fetus
Control group
Placebo

Outcomes
Primary outcome [1] 279741 0
The efficacy of mifepristone priming in achieving pregnancy interruption in mid-trimester fetal demise. This will be determined by assessing the median time to delivery in both groups with the primary aim being a 30% reduction in time to delivery in group 1.
Timepoint [1] 279741 0
At delivery point
Secondary outcome [1] 294349 0
Amount of blood loss. All patients at King Edward Memorial Hospital have their post partum blood loss weighed to accurately measure loss.
Timepoint [1] 294349 0
Peri-partum - 2 hours post placental delivery
Secondary outcome [2] 294350 0
% of cases with retained placenta
Timepoint [2] 294350 0
At one hour post devliery of the fetus
Secondary outcome [3] 294351 0
Side effects of mifepristone. Midwifery staff complete a patient observation form during and post delivery. This includes the amount of analgesia required and the presence or absence of pain, nausea, vomiting or diarrhoea.
Timepoint [3] 294351 0
4 hours post delivery
Secondary outcome [4] 294352 0
Maternal satisfaction is assessed using a patient question. A Likert scale with 0 being much worse than expected and 10 being much better than expected is used in relation to the following statements.

1. What did you think of the procedure
2. How would you rate your pain during the procedure
3. Would you recommend this method of termination to a friend in a similar situation
4. How much control did you feel you had

Patients are also given the opportunity for free form comment
Timepoint [4] 294352 0
Prior to discharge from hospital

Eligibility
Key inclusion criteria
All women who are admitted to King Edward Memorial Hospital for Women for pregnancy interruption for fetal death in utero between 14 and 28 weeks gestation will be invited to participate in the study
Minimum age
16 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women with more than three previous caesarean sections
Women not able to understand English
Multi fetal gestations

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)
The investigators will allocate a unique study participant number to the patient. This will be sequential and documented in a data set booked and in the patient notes.

This will also be recorded on the national inpatient medication chart.

The medication chart will be sent to pharmacy. The pharmacist will therefore be informed of the patients allocated number.

Prior to the study starting, the pharmacist will use a random sampling program to allocate case and controls to the unique study identifiers. The pharmacist will provide the mifepristone or placebo as appropriate.

Therefore, the study investigators, the participants and the staff administering the treament will be blinded to the patients group.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The patients will be allocated a study participant number. Prior to the commencement of recruiting, the pharmacists will use a random sampling program to assign each study participant number to treatment or placebo.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/08/2012
Actual
25/09/2012
Date of last participant enrolment
Anticipated
Actual
23/12/2016
Date of last data collection
Anticipated
Actual
30/01/2017
Sample size
Target
232
Accrual to date
Final
70
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 269985 0
Charities/Societies/Foundations
Name [1] 269985 0
Stillbirth Foundation Australia
Country [1] 269985 0
Australia
Funding source category [2] 270026 0
Hospital
Name [2] 270026 0
king Edward Memorial Hospital
Country [2] 270026 0
Australia
Funding source category [3] 289077 0
Charities/Societies/Foundations
Name [3] 289077 0
Women and Infants Research Foundation
Country [3] 289077 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Emma Allanson
Address
King Edward Memorial Hospital
374 Bagot Road
Subiaco WA 6008
Country
Australia
Secondary sponsor category [1] 268974 0
None
Name [1] 268974 0
Address [1] 268974 0
Country [1] 268974 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271951 0
WNHS and CAHS Human Research Ethics Committee
Ethics committee address [1] 271951 0
374 Bagot Road
Subiaco WA 6008
Ethics committee country [1] 271951 0
Australia
Date submitted for ethics approval [1] 271951 0
31/10/2011
Approval date [1] 271951 0
30/03/2012
Ethics approval number [1] 271951 0
1977/EW

Summary
Brief summary
Following fetal death in the second trimester of pregnancy, labour is usually induced to deliver the fetus. This induction process is usually conducted with the synthetic prostaglandin E1 analogue misoprostol. This prostaglandin, although not licensed for use in pregnancy, is now in common prescribed for labour induction in the second trimester with a large accumulated experience both within Australia and internationally. Since 1996, misoprostol has been used at King Edward Memorial Hospital (KEMH) as the principal agent for second trimester pregnancy induction with a non-viable fetus. The sequential combination of the antiprogesterone agent mifepristone and the prostaglanding misoprostol is an established and effective method for second trimester pregnancy termination. Prior studies have demonstrated a significant reduction in the duration of abortion with misoprostol when mifepristone priming is used. Three senior clinicians at KEMH, including the co-investigator Professor Jan Dickinson, have Authorised Prescriber status for use of mifepristone for pregnancy termination and following fetal death. Since January 2008 the combination of mifepristone and misoprostol has been used at KEMH in approximately 500 cases of first and second trimester pregnancy termination of pregnancy, predominantly for circumstances of severe fetal abnormality. Interestingly, there is very limited published data on the use of mifepristone in combination with misoprostol for induction of mid trimester fetal demise, Currently at KEMH misoprostol alone is the most frequent method used for delivery in the presence of a deceased fetus. This is most likely due to the restricted access to mifepristone and the absence of high quality comparative data of its efficacy. In this study we plan to compare the administration of mifepristone prior to misoprostol for induction after fetal death at 14-28 weeks gestation with the use of misoprostol alone (the current KEMH standard protocol). The primary aim of this research protocol will be to compare the induction commencement to delivery interval between these two regimes. Secondary aims of this study will be to assess the incidence of maternal side-effects for each of the two regimens, post partum blood loss, placental retention rates and the need for subsequent curettage for retained placental tissue. We will also review the women’s satisfaction with the two treatment regimens. The amount of progesterone and estrogen circulating in the blood of the women prior to induction will also be assayed, given that mifepristone works by blocking the effect of progesterone. It may be that the efficacy of mifepristone is related to the concentration of progesterone in the setting of fetal loss.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32536 0
Dr Emma Allanson
Address 32536 0
King Edward Memorial Hosptial
374 Bagot Road Subiaco
Western Australia 6008
Country 32536 0
Australia
Phone 32536 0
+61893402222
Fax 32536 0
Email 32536 0
[email protected]
Contact person for public queries
Name 15783 0
Dr Dr Emma Allanson
Address 15783 0
King Edward Memorial Hospital
374 Bagot Road
Subiaco
Western Australia
6008
Country 15783 0
Australia
Phone 15783 0
+61893402222
Fax 15783 0
Email 15783 0
[email protected]
Contact person for scientific queries
Name 6711 0
Dr Dr Emma Allanson
Address 6711 0
King Edward Memorial Hospital
374 Bagot Road
Subiaco
Western Australia
6008
Country 6711 0
Australia
Phone 6711 0
+61893402222
Fax 6711 0
Email 6711 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.