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

Trial Summary

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 data supports the effectiveness of the drug Etonogestrel Implant + Levonorgestrel for emergency contraception?

A study found that using oral levonorgestrel emergency contraception with the same-day initiation of an etonogestrel implant is effective, as it provides a low one-month pregnancy rate, supporting its use for emergency contraception. ^{1 2 3 4 5}

How does the drug Etonogestrel Implant differ from other emergency contraception options?

The Etonogestrel Implant is unique because it is a long-acting, subdermal (under the skin) contraceptive that provides up to 3 years of protection, unlike typical emergency contraceptives which are usually taken orally and provide short-term prevention. ^{1 2 4 5 6}

What is the purpose of this trial?

Intrauterine devices (IUDs) are highly effective to prevent pregnancy when used for emergency contraception (following unprotected intercourse in the last 3 days), but data are lacking for people who desire an etonogestrel (ENG) contraceptive implant in this situation. This proposal will identify the most effective way to start an implant for emergency contraception using a randomized controlled trial comparing pregnancy risk between those receiving the implant vs. the implant plus oral emergency contraception (EC). Data from this project will inform clinical practice and add another option, the implant, for those desiring a long acting, highly effective contraceptive method when they present for emergency contraception.

Research Team

Lori Gawron, MD

Principal Investigator

University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A prospective cohort study of early postpartum etonogestrel implant (Implanon®) use and its effect on duration of lochia. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Clinician satisfaction and insertion characteristics of a new applicator to insert radiopaque Implanon: an open-label, noncontrolled, multicenter trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of oral levonorgestrel emergency contraception with same day etonogestrel contraceptive implant: A prospective observational study. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Safety profile of etonogestrel contraceptive implant (Nexplanon® and Implanon®) reported in France]. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Neuropathy associated with etonogestrel implant insertion. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A life-threatening ectopic pregnancy with etonogestrel implant. [2014]