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NCT Number: NCT03065660

Mifepristone and Misoprostol Versus Misoprostol Alone in the Medical Management of Missed Miscarriage

Miscarriage is the most common complication of pregnancy. As many as 15-25% of pregnancies end in miscarriage, and the number of miscarriages in England is estimated to be approximately 125,000 per year. Miscarriage often brings not only physical pain, bleeding and risks of infection, but also psychological impacts on women and their families. This study will focus on women whose pregnancy sac remains inside the womb (known as a missed miscarriage) and opt for medical management of their miscarriage up to 13+6 weeks of pregnancy. NICE currently recommends that a drug called misoprostol (a vaginal pessary or oral tablet that makes the womb contract) should be used in the medical treatment of miscarriage. However, there is evidence to suggest that combining this drug with mifepristone (an oral tablet that reduces pregnancy hormones) may be more effective in treating miscarriage. Therefore, to test this in a clinical trial, participants will be allocated at random to receive either mifepristone followed by misoprostol, or a dummy drug (placebo) followed by misoprostol. Neither the participants nor the researchers will know what allocation is decided, which is necessary to test the treatments fairly. The main outcome of interest will be whether miscarriage is complete within 7 days of randomisation. If miscarriage is not complete then further treatment (more tablets or surgery) will be offered. A number of other key outcomes, such as the need for an operation, will also be assessed. We will also study the views and experience of the participants regarding the tablet treatment.

We anticipate that 710 women will be required to take part in the study to answer this question with confidence. We estimate that we would be able to recruit this many women in two years.

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Key information

Conditions

Missed Miscarriage Abortion, Incomplete Abortion, Spontaneous Female Urogenital Diseases and Pregnancy Complications Pregnancy Complications Urogenital Diseases

Age range

16 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Birmingham Heartlands Hospital, Birmingham, United Kingdom

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About this study

Aim: To investigate the clinical and cost-effectiveness of MifeMiso combination (mifepristone and misoprostol) versus misoprostol alone in the management of missed miscarriage.

Primary clinical objective: To test the hypothesis that treatment with mifepristone plus misoprostol is superior to misoprostol alone for the resolution of miscarriage within 7 days in women diagnosed with missed miscarriage by pelvic ultrasound scan in the first 13+6 weeks of pregnancy.

Key secondary objective:To test the hypothesis that the addition of mifepristone reduces the need for surgical intervention to resolve the miscarriage.

Other secondary objectives:

  • To evaluate if the addition of mifepristone reduces the need for further doses of misoprostol.
  • To evaluate if the addition of mifepristone improves other clinical outcomes including surgical intervention up to and including 7 days post-randomisation and after 7 days post-randomisation, duration of bleeding, infection, negative pregnancy test at 21 days post-randomisation, time from randomisation to discharge from EPU care, side effects and complications.
  • To evaluate if the addition of mifepristone improves patient satisfaction
  • To assess the cost-effectiveness of the combination of mifepristone and misoprostol in the medical management of missed miscarriage.

Economic objectives: To assess the cost-effectiveness of the combination of mifepristone and misoprostol in the medical management of missed miscarriage based on an outcome of additional cost per additional successfully managed miscarriage and additional cost per additional quality-adjusted life-year (QALY). Using a model-based economic evaluation we will further explore the cost-effectiveness of the medical management of missed miscarriage, as explored in the proposed trial, with alternative management strategies, such as surgical and expectant, based on available secondary sources.

Mixed-method evaluation objectives: To explore the satisfaction of patients who complete the trial protocol. The results of the satisfaction survey (CSQ-8) will act as a sampling frame to conduct semi-structured interviews to further investigate patient experiences and satisfaction with medical management of missed miscarriage.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Women diagnosed with missed miscarriage by pelvic ultrasound scan in the first 13+6 weeks of pregnancy that choose to have medical management of miscarriage.
  • Age 16 years and over
  • Willing and able to give informed consent.

Exclusion criteria

  • Women opting for alternative methods of miscarriage management (expectant or surgical)
  • Diagnosis of incomplete miscarriage.
  • Life threatening bleeding.
  • Contraindications to mifepristone or misoprostol use for example chronic adrenal failure, known hypersensitivity to either drug, haemorrhagic disorders and anticoagulant therapy, prosthetic heart valve or history of endocarditis, existing cardiovascular disease, severe asthma uncontrolled by therapy or inherited porphyria.
  • Participation in any other blinded, placebo-controlled trials of investigational medicinal products in pregnancy.
  • Previous participation in the MifeMiso trial
  • Woman not able to attend for day 6-7 ultrasound scan

Treatment and study plan

Mifepristone, Oral, 200 Mg

Drug

The Investigational Medicinal Product (IMP) is a single dose of 200mg mifepristone to be taken orally after confirmation of missed miscarriage by pelvic ultrasound scan.

Other names: Mifegyne

Placebo oral tablet

Drug

The placebo will be an oral tablet in the same form as the IMP, and identical in appearance.

Primary outcomes

  1. Failure to spontaneously pass the gestational sac within 7 days after randomisation

    Time frame: Within 7 days after randomisation

    To test the hypothesis that treatment with mifepristone plus misoprostol is superior to misoprostol alone for the resolution of miscarriage within 7 days in women diagnosed with missed miscarriage by pelvic ultrasound scan in the first 13+6 weeks of pregnancy.

Secondary outcomes

  1. Surgical intervention to resolve the miscarriage (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Surgical intervention to resolve the miscarriage

  2. Surgical intervention to resolve the miscarriage up to and including day 7 post-randomisation

    Time frame: From randomisation until day 7 post-randomisation

    Surgical intervention to resolve the miscarriage

  3. Surgical intervention to resolve the miscarriage after day 7 post-randomisation to discharge from EPU care

    Time frame: From day 8 post-randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Surgical intervention to resolve the miscarriage

  4. Need for further doses of misoprostol up to day 7 post-randomisation

    Time frame: After initial 800mcg dose of misoprostol at day 2 until day 7 post-randomisation

    Need for further doses of misoprostol up to day 7 post-randomisation

  5. Need for further doses of misoprostol up to discharge from EPU care

    Time frame: After initial 800mcg dose of misoprostol at day 2 until discharge from EPU care; assessed up to approximately 8 weeks

    Need for further doses of misoprostol up to discharge from EPU care

  6. Overall patient satisfaction score (measured using the CSQ-8 questionnaire and collected upon discharge from EPU care).

    Time frame: Within 6 weeks of discharge from EPU care

    Overall patient satisfaction score (measured using the CSQ-8 questionnaire and collected upon discharge from EPU care).

  7. Patient quality of life (Index value and overall health status measured using the EQ-5D-5L questionnaire

    Time frame: Completion on date of randomisation, day 6-7 post-randomisation or day of follow-up USS if different to day 6-7 and day 21 +/- 2 days post-randomisation. Completion of all patient quality of life assessments up to approximately 8 weeks post-randomisation

    Patient quality of life (Index value and overall health status measured using the EQ-5D-5L questionnaire and collected on date of randomisation, day 6-7 post-randomisation or day of follow-up USS if different to day 6-7 and day 21 +/- 2 days post-randomisation. If a woman obtains an initial positive pregnancy test result at day 21 +/- 2 days post-randomisation then a further EQ-5D-5L questionnaire is collected upon discharge from EPU care).

  8. Duration of bleeding reported by woman (days). (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Duration of bleeding reported by woman (days). (collected up to discharge from EPU care)

  9. Diagnosis of infection associated with miscarriage requiring outpatient antibiotic treatment (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Diagnosis of infection associated with miscarriage requiring outpatient antibiotic treatment (collected up to discharge from EPU care)

  10. Diagnosis of infection associated with miscarriage requiring inpatient antibiotic treatment (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Diagnosis of infection associated with miscarriage requiring inpatient antibiotic treatment (collected up to discharge from EPU care)

  11. Negative pregnancy test result 21 days (± 2 days) after randomisation.

    Time frame: 21 days (± 2 days) after randomisation.

    Negative pregnancy test result 21 days (± 2 days) after randomisation.

  12. Time from randomisation to discharge from EPU care (described using summary statistics only)

    Time frame: Time from randomisation to discharge from EPU care; assessed up to approximately 8 weeks

    Time from randomisation to discharge from EPU care.

  13. Blood transfusion required (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Blood transfusion required (collected up to discharge from EPU care)

  14. Side effects (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Side effects (collected up to discharge from EPU care)

  15. Death (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Death (collected up to discharge from EPU care)

  16. Any serious complications (collected up to discharge from EPU care)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Any serious complications (collected up to discharge from EPU care)

Other outcomes

  1. Outpatient or emergency visits

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Number of outpatient or emergency visits

  2. Inpatient admissions (nights in hospital)

    Time frame: From randomisation until discharge from EPU care; assessed up to approximately 8 weeks

    Number of inpatient admissions (nights in hospital)

Sponsors and collaborators

Lead sponsor

University of Birmingham

Other

Collaborators

  • Barts & The London NHS Trust
  • Birmingham Women's NHS Foundation Trust
  • City Hospitals Sunderland NHS Foundation Trust
  • Heart of England NHS Trust
  • King's College Hospital NHS Trust
  • Liverpool Women's NHS Foundation Trust
  • Oxford University Hospitals NHS Trust
  • Queen Mary University of London
  • Queen's Medical Center
  • Royal Infirmary of Edinburgh
  • Royal Victoria Infirmary
  • St Mary's Hospital, London
  • The Leeds Teaching Hospitals NHS Trust
  • University College London Hospitals
  • University Hospital Southampton NHS Foundation Trust
  • University Hospitals Coventry and Warwickshire NHS Trust
  • University of Edinburgh
  • University of Nottingham
  • University of Southampton
  • University of Warwick

Registry information

Official study title

A Randomised Placebo-controlled Trial of Mifepristone and Misoprostol Versus Misoprostol Alone in the Medical Management of Missed Miscarriage

Acronym: MifeMiso

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Feb 28, 2017
Registry last updated
Apr 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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