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

NCT03065660 | Completed Phase 3 DMC

• 3 other identifiers: RG_16-07615/160/022016-005097-35
• Study Type: interventional
• Target: 711
• Locations: 1 country
• Sites: 28

Brief Summary

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.

Conditions

Missed Miscarriage

Keywords

Missed miscarriage; Mifepristone; Misoprostol; Medical management

Outcome Measures

Primary Outcomes (1)

• Failure to spontaneously pass the gestational sac 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.

  Within 7 days after randomisation

Secondary Outcomes (16)

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

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

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

  From randomisation until day 7 post-randomisation

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

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

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

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

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

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

Other Outcomes (2)

• Outpatient or emergency visits

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

• Inpatient admissions (nights in hospital)

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

Study Arms (2)

Mifepristone

ACTIVE COMPARATOR

A single dose of oral mifepristone 200mg, followed by a single dose of vaginal, oral or sublingual misoprostol 800mcg 2 days later

Drug: Mifepristone, Oral, 200 Mg

Placebo

PLACEBO COMPARATOR

Oral placebo tablet followed by a single dose of vaginal, oral or sublingual misoprostol 800mcg 2 days later.

Drug: Placebo Oral Tablet

Interventions

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.

Also known as: Mifegyne

Mifepristone

Placebo Oral Tablet DRUG

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

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (28)

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Birmingham Women's Hospital

Birmingham, United Kingdom

Location

Southmead Hospital

Bristol, United Kingdom

Location

St Michael's Hospital

Bristol, United Kingdom

Location

Burnley General Hospital

Burnley, United Kingdom

Location

University Hospital Coventry

Coventry, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

Epsom Hospital

Epsom, United Kingdom

Location

St Helier Hospital

Epsom, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, United Kingdom

Location

Liverpool Women's Hospital

Liverpool, United Kingdom

Location

Chelsea and Westminster Hospital

London, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

Newham University Hospital

London, United Kingdom

Location

Royal London Hospital

London, United Kingdom

Location

St Thomas' Hospital

London, United Kingdom

Location

University College Hospital London

London, United Kingdom

Location

West Middlesex Hospital

London, United Kingdom

Location

Whipps Cross University Hospital

London, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, United Kingdom

Location

Queen's Medical Centre

Nottingham, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Princess Anne Hospital

Southampton, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, United Kingdom

Location

Princess of Wales Hospital

Swansea, United Kingdom

Location

Singleton Hospital

Swansea, United Kingdom

Location

Princess Royal Hospital

Telford, United Kingdom

Location

Related Links

• Trial website

MeSH Terms

Conditions

Abortion, Incomplete

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Abortion, Spontaneous; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Arri Coomarasamy

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants, investigators, research midwives/nurses and other attending clinicians will remain blind to the trial drug allocation throughout the duration of the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomised, parallel group, double-blind, placebo-controlled multicentre study, with health economic and mixed-methods evaluation.

Study Record Dates

• First Submitted: February 10, 2017
• First Posted: February 28, 2017
• Study Start: September 20, 2017
• Primary Completion: January 9, 2020
• Study Completion: January 9, 2020
• Last Updated: April 9, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (28)