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

April 29, 2020 updated by: Radboud University Medical Center

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

342

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • OLVG
      • Breda, Netherlands
        • Amphia Hospital
      • Eindhoven, Netherlands
        • Catharina Hospital
      • Groningen, Netherlands
        • Martini Hospital
      • Heerlen, Netherlands
        • Zuyderland Medical Centre
      • Nieuwegein, Netherlands
        • St. Antonius Hospital
      • Roermond, Netherlands
        • Laurentius Hosptial
      • The Hague, Netherlands
        • Haaglanden Medical Centre
      • Venlo, Netherlands
        • Viecuri Medical Centre
    • Gelderland
      • Arnhem, Gelderland, Netherlands, 6815 AD
        • Rijnstate
      • Nijmegen, Gelderland, Netherlands, 6532 SZ
        • Canisius Wilhelmina Hospital
      • Nijmegen, Gelderland, Netherlands, 6500 HB
        • Radboud University Medical Centre
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands, 3079 DZ
        • Maasstad Ziekenhuis

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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 Names:
  • 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: Misoprostol
Regular treatment with Misoprostol 800 mcg.
Other Names:
  • Cytotec
Drug: Mifepristone
Adding 600 mg of Mifepristone to the regular treatment with Misoprostol 800 mcg.
Other Names:
  • Mifegyne

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
six weeks after initial treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
At baseline, day four, two and six weeks after treatment
complications
Time Frame: six weeks after treatment
How many and which complications have occured?
six weeks after treatment
side effects
Time Frame: six weeks after treatment
Which side effects have patients experienced and to what degree?
six weeks after treatment
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.
up to six weeks after treatment
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
At baseline, day four, and two and six weeks after initial treatment.
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.
At baseline, day four, and two and six weeks after initial treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Canisius-Wilhelmina Hospital
Innovatiefonds Zorgverzekeraars

Investigators

  • Study Director: Frank P. Vandenbussche, Prof. Dr., Radboud UMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2018

Primary Completion (Actual)

January 23, 2020

Study Completion (Actual)

March 16, 2020

Study Registration Dates

First Submitted

July 2, 2017

First Submitted That Met QC Criteria

July 6, 2017

First Posted (Actual)

July 11, 2017

Study Record Updates

Last Update Posted (Actual)

May 1, 2020

Last Update Submitted That Met QC Criteria

April 29, 2020

Last Verified

September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 62449

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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