Comparison of Two Different Drug Regimens for Medical Treatment of Early Pregnancy Loss

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and efficacy of a combination of two drugs (mifepristone and misoprostol) to only one of these drugs (misoprostol) in medical management of missed miscarriage up to 13+6 weeks of pregnancy (early pregnancy loss). The investigators aim to enroll 220 patients within two years which would be enough to determine the difference between these two treatments with confidence.

Detailed Description
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Aim: To investigate the safety and efficacy of combination of mifepristone and misoprostol versus misoprostol alone in medical management of early pregnancy loss. Primary objective: To test the hypothesis that the sequential combination of mifepristone and misoprostol is superior to misoprostol alone for the complete evacuation of uterus in patients diagnosed with early pregnancy loss. Secondary objectives: To test the hypothesis that the addition of mifepristone reduces the need for further doses of misoprostol, duration of bleeding, complication rate and side effect frequency. The investigators will also evaluate if the addition of mifepristone improves patient satisfaction and quality of life. Women with a diagnosis of early pregnancy loss that opt for medical treatment and sign an informed consent will be included. The participants will be randomized to two groups. First group will receive oral mifepristone (600 mg) and the second group will not. The remaining course of treatment will be the same for both groups including giving misoprostol (800 mcg vaginally) 48 hours after receiving mifepristone for the first group or immediately for the second group. 24 hours after receiving first dose of misoprostol, one more dose of misoprostol (also 800 mcg vaginally) will be given if no pregnancy tissue is lost. Three weeks after medical treatment, primary and secondary outcomes will be assessed. In case of unsuccessful treatment (incomplete evacuation of uterus), surgical evacuation will be performed. 220 women will be randomized in a 1:1 ratio.

Official Title
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Comparison of Efficacy and Safety of Sequential Use of Mifepristone and Misoprostol vs Misoprostol Alone in Women With Early Pregnancy Loss: Randomized Controlled Trial

Conditions
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Abortion, Missed

Intervention / Treatment
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* Drug: Mifepristone, Oral, 200 Mg
* Drug: Misoprostol Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women diagnosed with missed miscarriage in the first 13+6 weeks of pregnancy opting for medical management Age 18 years and older Intra-uterine pregnancy Hemodynamically stable patient No signs of infection No signs of incomplete miscarriage 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 Hemodynamically unstable patient 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 Previous participation in this trial Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, parallel group, single center study. Before receiving vaginal misoprostol (800 mcg, repeated after 24 hours if no pregnancy tissue is lost), patients will be randomized to either oral mifepristone (600 mg) or nothing.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mifepristone and Misoprostol<br>Patients receive oral mifepristone (600 mg) 48 hours before medical treatment with vaginal misoprostol (800 mcg repeated after 24 hours if no pregnancy tissue is lost). | Drug: Mifepristone, Oral, 200 Mg<br>* Adding 600 mg of oral Mifepristone to the regular treatment with vaginal Misoprostol 800 mcg<br>* Other names: Mifegyne;Drug: Misoprostol Pill<br>* Regular treatment with vaginal Misoprostol 800 mcg<br>* Other names: Mispregnol;|
| Active Comparator: Misoprostol<br>Medical treatment with vaginal misoprostol (800 mcg repeated after 24 hours if no pregnancy tissue is lost). | Drug: Misoprostol Pill<br>* Regular treatment with vaginal Misoprostol 800 mcg<br>* Other names: Mispregnol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complete evacuation of uterus | Complete evacuation of uterus will be assessed by clinical and ultrasound examination three weeks after treatment. There should be no vaginal bleeding and no suspicion of retained products of conception on ultrasound scan (endometrial thickness <= 15 mm) to declare the treatment successful. | Three weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total misoprostol dose used | Total dose of misoprostol used during treatment | Up to three weeks after randomization | 
| Complications | Frequency of complications (by type) | Up to three weeks after randomization | 
| Side effects | Type and degree of side effects experienced as reported in the patient's diary | Up to three weeks after randomization | 
| Duration of vaginal bleeding | Duration of vaginal bleeding as reported in the patient's diary | Up to three weeks after randomization | 
| Hemoglobin change | Hemoglobin change from randomization until three weeks after treatment | At randomization and three weeks after randomization | 
| Patient quality of life | Overall health status measured using EuroQol-5 dimensions-5 levels questionnaire's (EQ-5D-5L) VAS (visual analog scale) score ranging from 0 to 100 where 0 represents worst health the participant can imagine and 100 represents the best health the participant can imagine | At randomization, 24 hours after taking first misoprostol dose and three weeks after randomization | 
| Patient satisfaction | Overall patient satisfaction with the treatment measured using validated paper-based Client Satisfaction Questionnaire (CSQ-8) score ranging from 4 to 32, where higher number represents higher satisfaction | Three weeks after randomization | 
| Indication for surgical treatment | Type and incidence of indications for surgical evacuation of uterus in case of unsuccessful medical treatment | Three weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Missed miscarriage, Misoprostol, Medical management, Mifepristone