Efficacy of mifepristone followed by misoprostol compared to misoprostol alone in first-trimester miscarriage treatment
| ISRCTN | ISRCTN11046192 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11046192 |
| Secondary identifying numbers | 3\2019 |
- Submission date
- 04/09/2020
- Registration date
- 12/09/2020
- Last edited
- 31/07/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
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.
Who can participate?
Healthy women aged 18 years 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 December 2021
Who is funding the study?
Hospital Senhora da Oliveira – Guimarães (Portugal)
Who is the main contact?
Beatriz Bettencourt Silva
beatrizbettsilva@gmail.com
Contact information
Scientific
Rua dos Cutileiros, Creixomil
Hospital Senhora da Oliveira - Serviço de Ginecologia e Obstetrícia
Guimarães
4835-044
Portugal
 ORCID ID |
0000-0002-1743-4329 |
|---|---|
| Phone | +351 (0)253 540 330 |
| beatrizsilva@hospitaldeguimaraes.min-saude.pt |
Public
Rua dos Cutileiros, Creixomil
Hospital Senhora da Oliveira - Serviço de Ginecologia e Obstetrícia
Guimarães
4835-044
Portugal
| Phone | +351 (0)253 540 330 |
|---|---|
| beatrizbettsilva@gmail.com |
Study information
| Study design | Single-center prospective interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant 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) |
| Scientific title | The role of Mifepristone on First-trimester miscarriage Treatment (MiFirsT) – a double-blind randomized controlled trial |
| Study acronym | MiFirsT |
| Study objectives | Mifepristone followed by vaginal misoprostol is more successful at treating first-trimester miscarriage than vaginal misoprostol alone. |
| Ethics approval(s) | Approved 26/02/2019, 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 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | 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 study start date | 03/12/2018 |
| Completion date | 16/12/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | 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%. |
| Total final enrolment | 216 |
| Key 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 years or older |
| Key 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 |
| Date of first enrolment | 10/04/2019 |
| Date of final enrolment | 25/11/2021 |
Locations
Countries of recruitment
- Portugal
Study participating centre
Creixomil
Guimarães
4835-044
Portugal
Sponsor information
Hospital/treatment centre
Rua dos Cutileiros
Creixomil
Guimarães
4835-044
Portugal
| Phone | +351 (0)253 540 330 |
|---|---|
| obstetricia@hospitaldeguimaraes.min-saude.pt | |
| Website | http://www.hospitaldeguimaraes.min-saude.pt/ |
"ROR" |
https://ror.org/00y0jw647 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/05/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal. The protocol is not published or available online. |
| IPD sharing plan | Current IPD sharing plan as of 31/07/2023: The datasets generated during and/or analysed during the current study will be available upon request from Beatriz Bettencourt Silva (email address: beatrizbettsilva@gmail.com). _____ Previous IPD sharing plan: The participant-level data is not expected to be made available because participants gave written informed consent to store the anonymized data and to share the study results with the scientific community, not specifically to share the individual data beyond the investigation team. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | 05/01/2023 | No | No | ||
| Basic results | 13/01/2023 | 13/01/2023 | No | No |
Additional files
Editorial Notes
31/07/2023: The IPD sharing plan has been changed and the IPD sharing summary updated accordingly.
13/01/2023: Basic results uploaded, IPD sharing statement added.
05/01/2023: Protocol uploaded (not peer reviewed). The intention to publish date has been changed from 16/12/2022 to 01/05/2023.
21/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2021 to 25/11/2021.
2. The overall trial end date has been changed from 15/02/2022 to 16/12/2021 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 30/04/2022 to 16/12/2022.
14/02/2022: Total final enrolment added.
26/10/2021: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/10/2021 to 31/12/2021.
2. The overall end date was changed from 31/12/2021 to 15/02/2022.
3. The intention to publish date was changed from 15/02/2022 to 30/04/2022.
4. The plain English summary was updated to reflect these changes.
18/08/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/08/2021 to 31/10/2021.
2. The overall trial end date has been changed from 31/10/2021 to 31/12/2021.
3. The intention to publish date has been changed from 15/01/2022 to 15/02/2022.
04/05/2021: The following changes have been made:
1. The recruitment end date has been changed from 30/04/2021 to 31/08/2021.
2. The overall trial end date has been changed from 31/05/2021 to 31/10/2021.
3. The intention to publish date has been changed from 01/12/2021 to 15/01/2022.
17/09/2020: Internal review.
10/09/2020: Trial's existence confirmed by Ethics Committee for Health of Hospital Senhora da Oliveira – Guimarães.
