Clinical trial NCT03212352: Comparing Two Medical Treatments for Early Pregnancy Failure.
Official title: Mifepristone and Misoprostol Versus Misoprostol Alone for Uterine Evacuation After Early Pregnancy Failure: a Randomized Double Blind Placebo-controlled Comparison (Triple M Trial)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Early Pregnancy Failure
Keywords: miscarriage
mifepristone
misoprostol
medical treatment
patient satisfaction
abortifacient agents
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Innovatiefonds Zorgverzekeraars
name: Canisius-Wilhelmina Hospital
First posted: 2017-07-11
Enrollment: 342
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Complete evacuation
timeFrame: six weeks after initial treatment
Secondary outcomes:
measure: patient satisfaction
timeFrame: At baseline, day four, two and six weeks after treatment
measure: complications
timeFrame: six weeks after treatment
measure: side effects
timeFrame: six weeks after treatment
measure: costs
timeFrame: up to six weeks after treatment
measure: Overall quality of health, as experienced by the patient.
timeFrame: At baseline, day four, and two and six weeks after initial treatment.
measure: Overall quality of health, as experienced by the patient.
timeFrame: At baseline, day four, and two and six weeks after initial treatment.
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: OLVG
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Groningen
country: Netherlands
facility: Martini Hospital
city: Heerlen
country: Netherlands
facility: Zuyderland Medical Centre
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Roermond
country: Netherlands
facility: Laurentius Hosptial
city: The Hague
country: Netherlands
facility: Haaglanden Medical Centre
city: Venlo
country: Netherlands
facility: VieCuri Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: Frank P. Vandenbussche, Prof. Dr.
role: STUDY_DIRECTOR
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