Plain English Summary
Background and study aims
First-trimester miscarriage (FTM) is the loss of a pregnancy during the first 13 weeks of pregnancy. It is a common event, occurring in 10 to 15% of all clinically identified pregnancies. Medical treatment of FTM allows a more predictable expulsion of products of conception compared to expectant management (waiting for the miscarriage to happen by itself naturally) and avoid the risks of surgical management. Misoprostol is a drug that is widely used for that effect. Vaginal administration of 800 μg is the most suitable treatment as a single dose, with success rates reaching 85%. Several studies have been investigating the combination of mifepristone with misoprostol in FTM and suggest an improvement in success rates compared to misoprostol alone. The aim of this study is to assess the effectiveness of mifepristone plus misoprostol compared to misoprostol alone for FTM. Additionally, the study intends to compare the rate of complications, adverse effects and treatment acceptability between the two groups, and evaluate treatment success according to clinical characteristics.
Who can participate?
Healthy women aged 18 or older diagnosed with FTM up to 9 weeks of gestation
What does the study involve?
Participants start the treatment under a physician’s supervision, taking orally a single-dose numbered white pill, which can contain 200 mg of either mifepristone or placebo. Participants will be randomly allocated to take mifepristone or placebo. Participants are instructed to complete the treatment with 800 μg of vaginal misoprostol 36 to 48 hours after the oral pill and another visit is scheduled in 2 to 3 weeks at the same service but not necessarily with the same physician. Demographic and clinical information is collected. The participants receive written information about FTM and medical treatment. They also complete a questionnaire about their experience, including date and time of misoprostol administration, adverse effects (nausea, vomiting, diarrhea, headache, dizziness, chills or fever), bleeding and pain intensity, pain medication use and acceptability. Vaginal misoprostol can be repeated about 48 hours later if no tissue is lost or if missed or incomplete miscarriage is diagnosed in follow-up. In each follow-up the physician performs a gynaecological exam and transvaginal ultrasound, reports symptoms or complications and the conduct adopted. In the center where the trial takes place it is common practice to reserve aspiration/curettage as a last-line treatment, although that possibility is always discussed with the patients. All participants are followed up until miscarriage resolution (diagnosis of complete miscarriage or surgical treatment).
What are the possible benefits and risks of participating?
Many Portuguese public hospitals offer only misoprostol for FTM treatment. Half of the study participants receive mifepristone, which may have a higher success rate. The surveillance and health care offered to participants is similar to any patient diagnosed with FTM. The combination with mifepristone (200 mg) is considered safe and none of the previously referred studies reported an increased risk of adverse events compared to misoprostol alone.
Where is the study run from?
Hospital Senhora da Oliveira – Guimarães (Portugal)
When is the study starting and how long is it expected to run for?
December 2018 to April 2021
Who is funding the study?
Hospital Senhora da Oliveira – Guimarães (Portugal)
Who is the main contact?
Beatriz Bettencourt Silva
beatrizbettsilva@gmail.com
Trial website
Contact information
Type
Scientific
Primary contact
Dr Beatriz Bettencourt Silva
ORCID ID
https://orcid.org/0000-0002-1743-4329
Contact details
Rua dos Cutileiros
Creixomil
Hospital Senhora da Oliveira - Serviço de Ginecologia e Obstetrícia
Guimarães
4835-044
Portugal
+351 (0)253 540 330
beatrizsilva@hospitaldeguimaraes.min-saude.pt
Type
Public
Additional contact
Dr Beatriz Bettencourt Silva
ORCID ID
https://orcid.org/0000-0002-1743-4329
Contact details
Rua dos Cutileiros
Creixomil
Hospital Senhora da Oliveira - Serviço de Ginecologia e Obstetrícia
Guimarães
4835-044
Portugal
+351 (0)253 540 330
beatrizbettsilva@gmail.com
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
3\2019
Study information
Scientific title
The role of Mifepristone on First-trimester miscarriage Treatment (MiFirsT) – a double-blind randomized controlled trial
Acronym
MiFirsT
Study hypothesis
Mifepristone followed by vaginal misoprostol is more successful at treating first-trimester miscarriage than vaginal misoprostol alone.
Ethics approval
Approved 26/02/2020, Ethics Committee for Health of Hospital Senhora da Oliveira – Guimarães (Rua dos Cutileiros, Creixomil, 4835-044 Guimarães; +351 253 540 330; comissaoetica@hospitaldeguimaraes.min-saude.pt), ref: 3\2019
Study design
Single-center prospective interventional randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet (originally in Portuguese, attending to the study population)
Condition
First trimester miscarriage (embryo without cardiac activity or anembryonic gestation) up to 9 weeks of gestation, diagnosed by transvaginal ultrasonographic criteria
Intervention
Adult women diagnosed with first-trimester miscarriage (up to 9 weeks of gestation), who are eligible and choose medical treatment, are randomized to either treatment with oral mifepristone (200 mg) or placebo, both followed by vaginal misoprostol (800 μg).
After eligibility and written informed consent, women initiate the treatment in the Obstetrics Emergency Service of Hospital Senhora da Oliveira – Guimarães under a physician’s supervision, taking orally a single-dose numbered white pill which contains either 200 mg of mifepristone (mifepristone group) or placebo (misoprostol-alone group). The pills are randomly numbered by the hospital's pharmacy in a 1:1 proportion and assigned to the participants in ascending order. Women are instructed to complete the treatment with 800 μg of vaginal misoprostol 36 to 48 hours after the oral pill and a revaluation is scheduled in 2-3 weeks at the same service. Participants and physicians involved in recruitment and follow-up are unaware of the treatment-group assignments (only the hospital pharmacy has the information about which numbered pills contained mifepristone). Vaginal misoprostol can be repeated approximately 48 hours after the first evaluation if no tissue is lost or in follow-up if missed or incomplete miscarriage is diagnosed. All patients maintain follow-up until complete miscarriage, which can take 2 months.
Intervention type
Drug
Phase
Not Applicable
Drug names
Mifepristone, misoprostol
Primary outcome measure
The success of medical treatment, defined as the complete evacuation of conception products by vaginal ultrasound and, thus, no need for surgical intervention. Treatment success is evaluated at the first follow-up appointment, 2 to 3 weeks after randomization (success rate at first follow-up) and at the second appointment, 3 to 5 weeks after randomization (success rate at second follow-up). The overall success rate and the rate of uterine aspiration/curettage is also reported.
Secondary outcome measures
1. Complications (namely severe bleeding or pelvic infection) evaluated by the physician at follow-up appointments or admission to emergency service
2. Adverse effects (nausea, vomiting, diarrhea, headache, dizziness, chills or fever) measured by questionnaire (binomial questions) to be answered after completing the initial treatment (mifepristone or placebo plus vaginal misoprostol)
3. Intensity of bleeding and pain measured by questionnaire (Likert-type scales) to be answered after completing the initial treatment (mifepristone or placebo plus vaginal misoprostol)
4. Acceptability of the treatment measured by questionnaire (classification of the treatment as “good”, “indifferent” or “bad” and if the participant would recommend it to a friend in the same clinical situation), to be answered after completing the initial treatment (mifepristone or placebo plus vaginal misoprostol)
5. Clinical characteristics that can influence treatment success (gravidity, parity, gestational age and diagnosis – embryo death or anembryonic gestation), assessed by the physician at randomization
Overall trial start date
03/12/2018
Overall trial end date
31/05/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Anembryonic or missed first-trimester miscarriage up to 9 weeks of gestation by transvaginal ultrasound (diagnosis criteria according to Society of Radiologists in Ultrasound Multispeciality Consensus Conference on Early First Trimester Diagnosis of Miscarriage and Exclusion of a Viable Intrauterine Pregnancy, October 2012)
2. Healthy women aged 18 or older
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Based on success rates reported by observational and interventional studies, the researchers calculate the estimated sample size of 202-256 participants with adequate power to detect a 17% difference in the rate of treatment success (73-84% in mifepristone-group; 56-67% in misoprostol-alone-group, Dunford et al., 2017, Schreiber et al., 2018), with a randomized ratio of 1:1, an overall significance level of 5% and a power of 80%.
Participant exclusion criteria
1. Diagnosis of inevitable or incomplete miscarriage
2. Suspicious of ectopic pregnancy or trophoblastic disease
3. Intrauterine device in place
4. Allergy to prostaglandins
5. Medical conditions contraindicating the treatment with misoprostol and/or mifepristone, namely intense vaginal bleeding with severe anemia or hemodynamic instability, suspicious of systemic infection, patients with hemorrhagic disorders or on anticoagulant therapy, patients with porphyria, uncontrolled heart disease, adrenal failure or on concurrent long-term corticosteroid therapy
Recruitment start date
10/04/2019
Recruitment end date
30/04/2021
Locations
Countries of recruitment
Portugal
Trial participating centre
Hospital Senhora da Olivieira – Guimarães, Serviço de Ginecologia e Obstetrícia
Rua dos Cutileiros
Creixomil
Guimarães
4835-044
Portugal
Sponsor information
Organisation
Hospital da Senhora da Oliveira Guimarães
Sponsor details
Rua dos Cutileiros
Creixomil
Guimarães
4835-044
Portugal
+351 (0)253 540 330
obstetricia@hospitaldeguimaraes.min-saude.pt
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Hospital Senhora da Oliveira Guimarães
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a peer-reviewed journal. The protocol is not published or available online.
IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/12/2021
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list