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Comparing Two Medical Treatments for Early Pregnancy Failure. (Triple M)

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: NCT03212352
Recruitment Status : Terminated (Advised by DSMB based on interim-analysis, highly significant difference.)
First Posted : July 11, 2017
Last Update Posted : May 1, 2020
Sponsor:
Collaborators:
Innovatiefonds Zorgverzekeraars
Canisius-Wilhelmina Hospital
Information provided by (Responsible Party):
Radboud University

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.


Condition or disease Intervention/treatment Phase
Early Pregnancy Failure Drug: Mifepristone Drug: Misoprostol Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 342 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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).
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 27, 2018
Actual Primary Completion Date : January 23, 2020
Actual Study Completion Date : March 16, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Misoprostol
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
Regular treatment with Misoprostol 800 mcg.
Other Name: Cytotec

Experimental: Misoprostol and Mifepristone
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
Adding 600 mg of Mifepristone to the regular treatment with Misoprostol 800 mcg.
Other Name: Mifegyne

Drug: Misoprostol
Regular treatment with Misoprostol 800 mcg.
Other Name: Cytotec




Primary Outcome Measures :
  1. Complete evacuation [ Time Frame: six weeks after initial treatment ]
    Whether or not complete evacuation (total endometrial thickness <15 mm) has been acquired will be assessed through ultrasonography.


Secondary Outcome Measures :
  1. patient satisfaction [ Time Frame: At baseline, day four, two and six weeks after treatment ]
    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)

  2. complications [ Time Frame: six weeks after treatment ]
    How many and which complications have occured?

  3. side effects [ Time Frame: six weeks after treatment ]
    Which side effects have patients experienced and to what degree?

  4. costs [ Time Frame: up to six weeks after treatment ]
    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.

  5. Overall quality of health, as experienced by the patient. [ Time Frame: At baseline, day four, and two and six weeks after initial treatment. ]
    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

  6. Overall quality of health, as experienced by the patient. [ Time Frame: At baseline, day four, and two and six weeks after initial treatment. ]
    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.



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:   No
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

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): NCT03212352


Locations
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Netherlands
Rijnstate
Arnhem, Gelderland, Netherlands, 6815 AD
Radboud University Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Canisius Wilhelmina Hospital
Nijmegen, Gelderland, Netherlands, 6532 SZ
Maasstad Ziekenhuis
Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
OLVG
Amsterdam, Netherlands
Amphia Hospital
Breda, Netherlands
Catharina Hospital
Eindhoven, Netherlands
Martini Hospital
Groningen, Netherlands
Zuyderland Medical Centre
Heerlen, Netherlands
St. Antonius Hospital
Nieuwegein, Netherlands
Laurentius Hosptial
Roermond, Netherlands
Haaglanden Medical Centre
The Hague, Netherlands
VieCuri Medical Centre
Venlo, Netherlands
Sponsors and Collaborators
Radboud University
Innovatiefonds Zorgverzekeraars
Canisius-Wilhelmina Hospital
Investigators
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Study Director: Frank P. Vandenbussche, Prof. Dr. Radboud UMC
  Study Documents (Full-Text)

Documents provided by Radboud University:
Study Protocol  [PDF] September 20, 2019
Statistical Analysis Plan  [PDF] February 3, 2020

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03212352    
Other Study ID Numbers: 62449
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: May 1, 2020
Last Verified: September 2019
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 Radboud University:
miscarriage
mifepristone
misoprostol
medical treatment
patient satisfaction
abortifacient agents
Additional relevant MeSH terms:
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Misoprostol
Mifepristone
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Anti-Ulcer Agents
Gastrointestinal Agents
Oxytocics
Abortifacient Agents, Steroidal
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