Etonogestrel Implant + Levonorgestrel for Emergency Contraception

Overseen By Sarah Elliott, MPH

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Lori Gawron

Must not be taking: CYP3A4 inducers, Steroid hormones

Disqualifiers: Pregnancy, Breastfeeding, Sterilization, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Immediate

790 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the effectiveness of the etonogestrel implant, a long-acting birth control placed under the skin, for emergency contraception compared to its use with an oral levonorgestrel pill. It targets individuals who recently had unprotected sex and seek a long-lasting birth control method. Participants will receive either the implant with a placebo pill or the implant with an oral levonorgestrel pill. Ideal candidates are those who had unprotected sex within the last three days, are biologically capable of becoming pregnant, and have a regular menstrual cycle. As a Phase 4 trial, this study involves an FDA-approved treatment and aims to understand its benefits for more patients.

Do I need to stop taking my current medications for the trial?

The trial requires participants to stop using any CYP3A4 inducer (a type of medication that affects how drugs are processed in the body) for 5 days. Additionally, you cannot use any other steroid hormones or certain contraceptives for specified periods before joining the trial.

What is the safety track record for the Etonogestrel Implant and Oral Levonorgestrel?

Research has shown that the etonogestrel implant is generally safe. In studies with 942 women, the most common side effects included changes in menstrual bleeding, headaches, and weight gain. About 10% of users experienced changes in bleeding, and some reported headaches and acne. Insertion may cause discomfort, such as pain or bruising.

For oral levonorgestrel, studies indicate that common side effects include stomach pain, dizziness, and headaches. Users may also feel nauseous and tired. These side effects are usually mild and temporary.

Both treatments have been approved and used in other situations, suggesting they are well-tolerated. While some side effects can occur, they are generally not severe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of the etonogestrel implant with oral levonorgestrel for emergency contraception because it offers a unique dual approach to preventing pregnancy. Unlike current options, which typically involve either a single hormone method (like Plan B, which uses only levonorgestrel) or a copper IUD, this combination uses both the long-acting implant and an oral dose of levonorgestrel. The implant provides ongoing contraception, while the oral levonorgestrel offers immediate action, potentially enhancing effectiveness in preventing pregnancy after unprotected sex. This innovative combination could provide more comprehensive protection than current emergency contraception options.

What evidence suggests that this trial's treatments could be effective for emergency contraception?

Research has shown that the etonogestrel implant, which participants in this trial may receive, is a highly effective long-term birth control method. In a large study, none of the 204 women using the implant for five years became pregnant. The implant releases hormones that prevent the release of an egg.

For the oral levonorgestrel pill, another treatment option in this trial, studies indicate it can reduce the chance of pregnancy by up to 91% if taken immediately after unprotected sex. It remains effective as an emergency contraceptive for up to 96 hours (four days) after sex. This trial will compare these two strong options for preventing pregnancy after unprotected sex. ^{6 7 8 9 10}

Who Is on the Research Team?

Lori Gawron, MD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for individuals who've had unprotected intercourse within the last 72 hours, are able to get pregnant, speak English or Spanish, have regular menstrual cycles (21-35 days), and can follow study rules. They must know their last period date (+/- 3 days) and have a working phone. It's not for those currently pregnant or breastfeeding, with contraindications to ENG/LNG contraceptives, sterilized, with an IUD/implant already in place, unexplained vaginal bleeding, prior EC use in the same cycle or allergies/intolerance to LNG/ENG.

Inclusion Criteria

Willing to comply with the study requirements

Known last menstrual period (+/- 3 days)

I have a working cell phone.

Exclusion Criteria

Current pregnancy (+urine pregnancy test in clinic)

I cannot use certain birth control methods due to health reasons.

Sterilization or has an IUD or contraceptive implant in place

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive the etonogestrel contraceptive implant with either oral levonorgestrel or placebo

Immediate

1 visit (in-person)

Follow-up

Participants are monitored for efficacy and ovulation frequency after implant insertion

4 weeks

1 visit (in-person), 1 follow-up call

Long-term Follow-up

Participants are assessed for implant continuation and satisfaction

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Etonogestrel Implant
• Oral Levonorgestrel

Trial Overview The study tests if starting an etonogestrel (ENG) contraceptive implant alone is as effective for emergency contraception as when combined with oral Levonorgestrel (LNG). Participants will be randomly assigned to receive either the implant plus oral LNG or the implant plus a placebo. The goal is to determine which method better prevents pregnancy after unprotected sex.

How Is the Trial Designed?

Group I: Etonogestrel contraceptive implant with oral levonorgestrel Active Control 1 Intervention

Patients will be randomized 1:1 to each arm and will receive the contraceptive implant with a same-day encapsulated pill with either oral levonorgestrel 1.5mg

Group II: Etonogestrel contraceptive implant with placebo Placebo Group 1 Intervention

Patients will be randomized 1:1 to each arm and will receive the contraceptive implant with a same-day encapsulated pill with placebo X 1 dose

Etonogestrel Implant is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Implanon/Nexplanon for:

• Contraception

Approved in United States as Implanon/Nexplanon for:

• Contraception

Approved in Canada as Implanon/Nexplanon for:

• Contraception

Who Is Running the Clinical Trial?

Lori Gawron

Lead Sponsor

Trials

1

Recruited

790+

Planned Parenthood Association of Utah

Collaborator

Trials

1

Recruited

790+

Published Research Related to This Trial

Etonogestrel contraceptive implants are highly effective for long-term hormonal contraception, but this case report highlights a rare instance of a ruptured ectopic pregnancy in a patient using the implant for less than 2 years.

The case suggests that body mass index (BMI) may influence the effectiveness of the implant, indicating a need for further research on how weight affects contraceptive efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A life-threatening ectopic pregnancy with etonogestrel implant. Bouquier, J., Fulda, V., Bats, AS., et al.[2014]

In a study of 152 postpartum patients, early insertion of the Implanon contraceptive implant did not significantly affect the duration of lochia, with both treatment and control groups experiencing similar median durations of around 25 days.

Out of the women who had Implanon inserted, 17.7% experienced prolonged or intermittent vaginal bleeding beyond 50 days postpartum, leading to their implant removal, indicating a potential side effect of the contraceptive method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective cohort study of early postpartum etonogestrel implant (Implanon®) use and its effect on duration of lochia. Dobromilsky, KC., Allen, PL., Raymond, SH., et al.[2019]

In a study involving 160 emergency contraception clients, the overall pregnancy rate after same-day initiation of an etonogestrel implant and oral levonorgestrel emergency contraception was found to be 1.32%, which is within the expected range for oral emergency contraception methods.

When focusing on pregnancies that occurred within 5 days of unprotected intercourse, the pregnancy rate dropped to 0.66%, suggesting that this combined approach is effective in reducing the risk of unintended pregnancies shortly after unprotected sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oral levonorgestrel emergency contraception with same day etonogestrel contraceptive implant: A prospective observational study. Gawron, LM., Sexsmith, CD., Carter, G., et al.[2023]

A case study highlighted that improper insertion of the etonogestrel contraceptive implant (Implanon®) can lead to forearm pain and hypoesthesia due to contact with the medial cutaneous nerve, emphasizing the need for correct insertion techniques.

The newer Nexplanon® implant features a redesigned applicator aimed at improving insertion accuracy and reducing the risk of nerve injury during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropathy associated with etonogestrel implant insertion. Brown, M., Britton, J.[2022]

The new next-generation applicator (NGA) for the radiopaque etonogestrel (ENG) implant was well-received by both experienced and inexperienced clinicians, with nearly all expressing satisfaction after multiple insertions.

The radiopaque implant was successfully visible on X-ray imaging, and while most insertions were easy, adherence to proper insertion instructions was crucial to avoid errors, as three incorrect insertions occurred due to noncompliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial. Mansour, D., Mommers, E., Teede, H., et al.[2022]

Over a 10-year period, 5433 adverse effects (AEs) were reported for the etonogestrel contraceptive implant, with only 7% classified as serious, indicating that while AEs are common, they are mostly not severe.

The introduction of Nexplanon® has significantly reduced complications related to insertion and migration of the implant, highlighting improvements in safety and efficacy compared to its predecessor, Implanon®.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety profile of etonogestrel contraceptive implant (Nexplanon® and Implanon®) reported in France]. Simon, C., Agier, MS., Béné, J., et al.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38008305/

Efficacy of oral levonorgestrel emergency contraception with ... A positive pregnancy test occurred in 2 participants resulting in an overall pregnancy rate of 1.32% (95% confidence interval 0.23%-5.19%).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S001078242300464X

Efficacy of oral levonorgestrel emergency contraception ... A total of 160 emergency contraception clients (7.6% of 2106 approached) enrolled and 153 had 1-month pregnancy outcomes. A positive pregnancy test occurred in ...

3. contraceptionjournal.org contraceptionjournal.org/article/S0010-7824(24)00188-4/fulltext

Addendum to “Efficacy of oral levonorgestrel emergency ... This yielded an EC pregnancy risk of 0.66% (95% CI 0.03%–4.19%). During the assessment of secondary outcomes, for which participants completed ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05237141

Etonogestrel Implant as Emergency Contraception Based on data from the Food and Drug Administration label for Nexplanon, etonogestrel rises to levels associated with ovulation suppression within 8 hours of ...

5. acog.org acog.org/clinical/clinical-guidance/practice-bulletin/articles/2017/11/long-acting-reversible-contraception-implants-and-intrauterine-devices

Long-Acting Reversible Contraception Implants and ... The etonogestrel implant is effective for at least 4 years.One large study reported no pregnancies among 204 women using the etonogestrel implant for 5 years ...

6. organonpro.com organonpro.com/en-us/product/nexplanon/

NEXPLANON® (etonogestrel implant) 68 mg Radiopaque The most common adverse reactions (≥10%) reported in clinical trials were headache (24.9%), vaginitis (14.5%), weight increase (13.7%), acne (13.5%), breast ...

7. nexplanon.com nexplanon.com/side-effects/

Risks and Side Effects of NEXPLANON® (etonogestrel ... The most common side effect of NEXPLANON is a change in your normal menstrual bleeding pattern. In studies, one out of ten women stopped using the implant.

8. mayoclinic.org mayoclinic.org/drugs-supplements/etonogestrel-intradermal-route/description/drg-20069037

Etonogestrel (intradermal route) - Side effects & uses This medicine may cause several problems related to insertion and removal, including pain, irritation, swelling, bruising, scarring, or other complications.

9. organon.com organon.com/docs/product/safety-data-sheets/Etonogestrel%20Formulation%20(Implanon)_IN_6N.pdf

SAFETY DATA SHEET Etonogestrel Formulation (Implanon) Most important symptoms and effects, both acute and delayed. : May be harmful if swallowed. May damage fertility. Contact with dust can cause mechanical ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2015/021529s011lbl.pdf

NEXPLANON (etonogestrel implant) Label In clinical trials involving 942 women who were evaluated for safety, change in menstrual bleeding patterns (irregular menses) was the most common adverse ...