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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03065660
Recruitment Status : Completed
First Posted : February 28, 2017
Last Update Posted : April 9, 2020
Sponsor:
Collaborators:
Birmingham Women's NHS Foundation Trust
Royal Infirmary of Edinburgh
Royal Victoria Infirmary
City Hospitals Sunderland NHS Foundation Trust
Liverpool Women's NHS Foundation Trust
The Leeds Teaching Hospitals NHS Trust
Barts & The London NHS Trust
Queen's Medical Centre
Heart of England NHS Trust
University Hospitals Coventry and Warwickshire NHS Trust
Oxford University Hospitals NHS Trust
St Mary's Hospital, London
University College London Hospitals
University Hospital Southampton NHS Foundation Trust
King's College Hospital NHS Trust
University of Edinburgh
University of Nottingham
Queen Mary University of London
University of Warwick
University of Southampton
Information provided by (Responsible Party):
University of Birmingham

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.


Condition or disease Intervention/treatment Phase
Missed Miscarriage Drug: Mifepristone, Oral, 200 Mg Drug: Placebo Oral Tablet Phase 3

Detailed Description:

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:

  1. To evaluate if the addition of mifepristone reduces the need for further doses of misoprostol.
  2. 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.
  3. To evaluate if the addition of mifepristone improves patient satisfaction
  4. 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 711 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomised, parallel group, double-blind, placebo-controlled multicentre study, with health economic and mixed-methods evaluation.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Participants, investigators, research midwives/nurses and other attending clinicians will remain blind to the trial drug allocation throughout the duration of the trial.
Primary Purpose: Treatment
Official Title: A Randomised Placebo-controlled Trial of Mifepristone and Misoprostol Versus Misoprostol Alone in the Medical Management of Missed Miscarriage
Actual Study Start Date : September 20, 2017
Actual Primary Completion Date : January 9, 2020
Actual Study Completion Date : January 9, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Miscarriage

Arm Intervention/treatment
Active Comparator: Mifepristone
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
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 Name: Mifegyne

Placebo Comparator: Placebo
Oral placebo tablet followed by a single dose of vaginal, oral or sublingual misoprostol 800mcg 2 days later.
Drug: Placebo Oral Tablet
The placebo will be an oral tablet in the same form as the IMP, and identical in appearance.




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03065660


Locations
Show Show 28 study locations
Sponsors and Collaborators
University of Birmingham
Birmingham Women's NHS Foundation Trust
Royal Infirmary of Edinburgh
Royal Victoria Infirmary
City Hospitals Sunderland NHS Foundation Trust
Liverpool Women's NHS Foundation Trust
The Leeds Teaching Hospitals NHS Trust
Barts & The London NHS Trust
Queen's Medical Centre
Heart of England NHS Trust
University Hospitals Coventry and Warwickshire NHS Trust
Oxford University Hospitals NHS Trust
St Mary's Hospital, London
University College London Hospitals
University Hospital Southampton NHS Foundation Trust
King's College Hospital NHS Trust
University of Edinburgh
University of Nottingham
Queen Mary University of London
University of Warwick
University of Southampton
Investigators
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Principal Investigator: Arri Coomarasamy University of Birmingham
Additional Information:
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Responsible Party: University of Birmingham
ClinicalTrials.gov Identifier: NCT03065660    
Other Study ID Numbers: RG_16-076
15/160/02 ( Other Grant/Funding Number: NIHR HTA )
2016-005097-35 ( EudraCT Number )
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: April 9, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Birmingham:
Missed miscarriage
Mifepristone
Misoprostol
Medical management
Additional relevant MeSH terms:
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Abortion, Spontaneous
Abortion, Missed
Pregnancy Complications
Mifepristone
Abortifacient Agents, Steroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Contraceptives, Postcoital, Synthetic
Contraceptives, Postcoital
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents