Comparing Two Medical Treatments for Early Pregnancy Failure.

Study Overview
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Brief Summary
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This study aims to compare whether a combination of two drugs (Mifepristone and misoprostol) are superior compared to using only one of these drugs (Misoprostol) as medical treatment for a miscarriage. Women in whom early pregnancy failure, 6-14 weeks postmenstrual, is ultrasonographically confirmed qualify for this study. It is expected that the combination of Mifepristone and Misoprostol is more effective in reaching complete evacuation, and therefore can prevent more invasive treatment such as curettage.

Detailed Description
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This study will test the hypothesis that, in early pregnancy failure, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation of products of conception (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes). The trial will be performed multi-centred (hospitals), prospectively, two-armed, randomized, double-blinded and placebo-controlled. Women with ultrasonographically confirmed early pregnancy failure (6-14 weeks postmenstrual), managed expectantly for at least one week, can be included. Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients will be randomized to oral mifepristone (600mg) or oral placebo (identical in appearance). The investigators aim to randomize 460 women in a 1:1 ratio, stratified by centre. After six weeks, the primary endpoint, complete or incomplete evacuation, will be determined

Official Title
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Mifepristone and Misoprostol Versus Misoprostol Alone for Uterine Evacuation After Early Pregnancy Failure: a Randomized Double Blind Placebo-controlled Comparison (Triple M Trial)

Conditions
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Early Pregnancy Failure

Intervention / Treatment
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* Drug: Mifepristone
* Drug: Misoprostol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early pregnancy failure, 6-14 weeks postmenstrual with a crown-rump length ≥ 6mm and no cardiac activity OR a crown-rump length <6mm and no fetal growth at least one week later OR a gestational sac with absent embryonic pole for at least one week. At least one week after diagnosis OR a discrepancy of at least one week between crown-rump length and calendar gestational age Intra-uterine pregnancy Women aged above 16 years Hemodynamic stable patient No signs of infection No signs of incomplete abortion No contraindications for mifepristone or misoprostol Exclusion Criteria: Patient does not meet inclusion criteria, discovered after randomization Inability to give informed consent Known clotting disorder or use of anticoagulants Known risk factors for, or presence of, a cardiovascular disease Language barrier

Ages Eligible for Study
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Minimum Age: 16 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: Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients will be randomized to oral mifepristone (600mg) or oral placebo (identical in appearance).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Misoprostol<br>Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients receive an oral placebo. | Drug: Misoprostol<br>* Regular treatment with Misoprostol 800 mcg.<br>* Other names: Cytotec;|
| Experimental: Misoprostol and Mifepristone<br>Before medical treatment with misoprostol (two doses 400mcg (four hours apart), repeated after 24 hours if no tissue is lost), patients receive oral mifepristone (600mg). | Drug: Mifepristone<br>* Adding 600 mg of Mifepristone to the regular treatment with Misoprostol 800 mcg.<br>* Other names: Mifegyne;Drug: Misoprostol<br>* Regular treatment with Misoprostol 800 mcg.<br>* Other names: Cytotec;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete evacuation | Whether or not complete evacuation (total endometrial thickness <15 mm) has been acquired will be assessed through ultrasonography. | six weeks after initial treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patient satisfaction | To assess how satisfied patient are with the treatment they underwent. Patient satisfaction with treatment will be measured using The Client Satisfaction Questionnaire (CSQ-8, digital) | At baseline, day four, two and six weeks after treatment | 
| complications | How many and which complications have occured? | six weeks after treatment | 
| side effects | Which side effects have patients experienced and to what degree? | six weeks after treatment | 
| costs | To evaluate which medical treatment strategy is cost-effective, volumes of health care consumed will additionally be measured prospectively alongside the clinical trial together with cost associated with productivity losses. Costs of medical interventions (direct costs) and costs resulting from productivity loss (indirect costs) will be taken into account. Resource uses will be recorded in the case report forms. Standardized unit costs will be calculated using the Dutch manual for costing in economic evaluations and standardised costs. | up to six weeks after treatment | 
| Overall quality of health, as experienced by the patient. | To measure the quality of the health status of the patients, a validated so-called health-related quality of life (HRQoL) instrument will be used: the Short Form 36 health survey | At baseline, day four, and two and six weeks after initial treatment. | 
| Overall quality of health, as experienced by the patient. | To measure the quality of the health status of the patients,a validated so-called health-related quality of life (HRQoL) instrument will be used: the EuroQol-5D. | At baseline, day four, and two and six weeks after initial treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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miscarriage, mifepristone, misoprostol, medical treatment, patient satisfaction, abortifacient agents