Early menstrual induction - Proof of concept study

Plain English summary of protocol

Background and study aims
Emergency contraception (EC) refers to a method of contraception that can be used to prevent pregnancy after sexual intercourse. Currently, the available EC methods only work up until 5 days after unprotected intercourse. This means that women who have not been able to access EC, and do not wish to be pregnant, will have to wait and see if they have become pregnant and obtain an abortion if desired. In the current study, we investigate the effect of a new EC treatment which can be used between 5 days after intercourse and the day before expected menstruation.

In the proof-of-concept study, 80 women who have missed the current EC window, will be given levonorgestrel (progesterone) followed by mifepristone (anti-progesterone) 48 hours later to induce menstruation, as a form of early menstrual induction. If effective, this intervention will increase options available to women, filling an important gap in the work towards preventing unwanted pregnancies and potentially unsafe abortions.

Who can participate?
Women (18-45 years old) can join the study when they have had unprotected intercourse and were too late to use the standard emergency contraception (such as the morning-after pill). They should not have reached the day of your expected menstruation. There are some specific criteria to join the study which include: having a regular menstrual cycles (25-35 days), intend to end the pregnancy if confirmed, agree not to use other contraception methods during the study period.

What does the study involve?
The study involves the following four parts:
1. Blood is drawn from women who meet the inclusion- and exclusion criteria to measure plasma βhCG. If the value is > 10 mIU/ml the women are included in the study. If lower than 10 mIU/ml, the women are asked to come back in 5 days, if the plasma βhCG remains below 10 mIU/ml they cannot join the study.
2. Women who have a positive βhCG test result either at the first or second testing will be included in the study and receive the first intervention. The participants will receive 1.5mg levonorgestrel once as a single oral intake at the facility immediately upon enrolment.
3. After the intake of levonorgestrel, the women will be sent home and asked to return to the health facility 2 days later, where they will be given 200mg mifepristone as a single dose oral intake.
4. On Day 14 the women will be invited back to the health facility for plasma βhCG measurement. If the plasma βhCG is < 10 mIU/ml, the treatment will be regarded as successful, and no further intervention is needed. If the plasma βhCG is > 10 mIU/ml, the intervention has failed, and the woman will be offered the option of pregnancy termination.
During the 14 days, the women are asked to fill out a questionnaire.

What are the possible benefits and risks of participating?
The early menstrual induction process maybe associated with cramp-like pain and bleeding that may be heavy at times. Also, women may experience other side-effects, like fever, chills, nausea, vomiting or diarrhoea. These risks of having induced menses are the same whether women take part in this study or not.
Blood samples
The drawing of blood (5ml) will be performed by skilled and qualified medical staff. It has very limited risks, such as being uncomfortable or may give some stress.
Medication
Both medications used in the study (levonorgestrel and mifepristone) are registered and approved for usage.
The intake of 1.5 mg levonorgestrel could lead to the following side effects:
Heavier or lighter than usual menstrual bleeding; spotting or bleeding between menstrual periods; nausea; vomiting; diarrhoea; tiredness; headache; dizziness; breast pain or tenderness.
The intake of 200 mg mifepristone could lead to the following side effects:
Vaginal bleeding or spotting; cramps; pelvic pain; vaginal burning, itching, or discharge; headache.

There is a possibility that the treatment with levonorgestrel and mifepristone is not successful to prevent the unintended pregnancy and that the women will be referred for follow-up care. This can cause emotional burden for them, as they will have to consider their options to terminate or continue the pregnancy.

Where is the study run from?
Chulalongkorn University Hospital (Thailand)

When is the study starting and how long is it expected to run for?
May 2021 to December 2023

Who is funding the study?
World Health Organization (Switzerland)

Who is the main contact?
Prof. Unnop Jaisamrarn, Unnop.J@Chula.ac.th

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• Thailand

Study participating centre

Sponsor information

Concept Foundation
Research organisation

Avenue de Sécheron 15
Geneva
1202
Switzerland

Phone	+41 22 734 2560/1
Email	info@conceptfoundation.org
Website	http://www.conceptfoundation.org/
"ROR"	https://ror.org/039k72k82

Funders

Funder type

Research organisation

Results and Publications

Editorial Notes

03/06/2024: The intention to publish date was changed from 01/05/2024 to 01/08/2024.
26/10/2023: The following changes were made to the trial record:
1. The overall end date was changed from 15/08/2022 to 31/12/2023.
2. The intention to publish date was changed from 01/09/2023 to 01/05/2024.
3. The plain English summary was updated to reflect these changes.
19/07/2021: Trial's existence confirmed by Institutional Review Board Faculty of Medicine, Chulalongkorn University