Evaluation of Immediate Versus Delayed Intrauterine Levonorgestrel Insertion Post-Medical Abortion: A Randomized Multicenter Study

The primary objective of this study is to evaluate whether the **immediate insertion** of intrauterine contraception (IUC) is superior to insertion at 2-4 weeks post-abortion in terms of the number of women using IUC as contraception at 6 months post-abortion. This is clinically relevant as it may influence post-abortion contraceptive practices and improve long-term contraceptive use, thereby reducing the risk of unintended pregnancies.

Secondary objectives include assessing if immediate insertion of intrauterine contraception is non-inferior to delayed insertion concerning safety and acceptability. This evaluation is crucial for understanding the broader implications of immediate IUC insertion on patient safety and satisfaction, which can inform clinical guidelines and patient counseling.

The clinical trial focuses on **post medical abortion contraception** and involves a study population exclusively comprising females. Participants are required to be above 18 years of age, eligible for medical abortion, and opting for post-abortion intrauterine contraception. They must also be able and willing to comply with planned follow-up. The trial does not include male subjects and involves a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria emphasize the ability to adhere to follow-up protocols, ensuring that participants are committed to the study's requirements.

The clinical trial is designed to evaluate the effectiveness of **intrauterine contraception** (IUC) when inserted immediately versus 2-4 weeks post medical abortion. This study is an open-label, randomized, multicenter trial. The primary objective is to determine if immediate insertion of IUC is superior in terms of the number of women using IUC as contraception at six months post-abortion. The trial is expected to run from January 7, 2020, to June 30, 2025, with participant involvement lasting up to 12 months post-insertion.

Participants will be randomly assigned to either immediate or delayed IUC insertion groups. The study will include several visits: an initial screening visit to confirm eligibility, the insertion visit, and follow-up visits at 3, 6, and 12 months post-insertion. The inclusion criteria require participants to be over 18 years old, eligible for medical abortion, opting for post-abortion IUC, and able to comply with follow-up. There are no specified exclusion criteria.

The primary endpoint is the proportion of women using IUC at six months post-abortion. Secondary endpoints include the use of IUC at 3, 6, and 12 months, ease of insertion, pain assessment, post-abortion bleeding, and reasons for non-attempted insertion. The study will also evaluate the acceptability of IUC, expulsion rates, complications, and any surgical procedures required. Participants may be terminated early from the study if they experience adverse events or are unable to comply with the study protocol.

The clinical trial involves the use of three **intrauterine delivery systems** containing **levonorgestrel** as the active substance. The first experimental medication is Mirena, which is an intrauterine device delivering 20 micrograms of levonorgestrel per 24 hours. The pharmaceutical form is an intrauterine delivery system, and it is administered via intrauterine use. The maximum treatment period for Mirena is 96 months. The device is manufactured by Bayer AB and is not a pediatric formulation. The maximum daily dose is 1 microgram, and participant compliance is monitored through regular follow-ups.

The second experimental medication is Kyleena, which delivers 19.5 mg of levonorgestrel. Similar to Mirena, Kyleena is also an intrauterine delivery system administered via intrauterine use. The maximum treatment period for Kyleena is 60 months. This device is produced by Bayer OY and is also not intended for pediatric use. The maximum daily dose is 1 microgram, and compliance is ensured through scheduled clinical assessments.

The third experimental medication is Jaydess, which delivers 13.5 mg of levonorgestrel. Jaydess is administered as an intrauterine delivery system with a maximum treatment period of 36 months. It is manufactured by Bayer OY and is not a pediatric formulation. The maximum daily dose is 1 microgram, and participant adherence is monitored through periodic evaluations.

All three intrauterine devices are classified under the ATC code G02BA03, indicating they are plastic IUDs with progestogen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are used in this study. The trial aims to evaluate the effectiveness of immediate versus delayed insertion of these intrauterine contraceptives following medical abortion.

Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the proportion of women using intrauterine contraception (IUC) as contraception at 6 months post-abortion. This will determine if immediate insertion of IUC is superior to delayed insertion at 2-4 weeks post-abortion. Secondary endpoints include the use of IUC at 3, 6, and 12 months post-insertion, evaluated through telephone or e-mail follow-up. This will include continued use, voluntary or involuntary discontinuation, and reasons for discontinuation, as well as subsequent use of other contraceptive methods.

Additional secondary endpoints involve the difference in the proportion of women who successfully have the IUC inserted, ease of insertion as judged by healthcare providers, and pain at the time of insertion measured using a Visual Analogue Scale (VAS). Post-abortion bleeding, reasons for non-attempted insertion, and pregnancies occurring during the 6 and 12-month follow-up will also be assessed. Acceptability of immediate and delayed insertion of IUC will be evaluated by asking women if they would recommend the procedure to a friend, and the expulsion rate during 12 months following insertion will be monitored. Complications such as adverse events, bleeding requiring treatment, uterine perforations, infections, and surgical procedures will be recorded. The proportion of surgical procedures in total and for each study site will also be documented.