Etonogestrel (ENG) Implant Insertion for Emergency Contraception With Oral Levonorgestrel (LNG) vs Placebo

Study Overview
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Brief Summary
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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.

Detailed Description
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Oral emergency contraception (EC), is commonly used after recent unprotected intercourse to avoid undesired pregnancy, but does not provide ongoing contraception. Rigorous data allow for use of intrauterine devices (IUDs) as both EC and ongoing contraception, but EC efficacy data on use of the etonogestrel (ENG) implant, is lacking. The CDC Selected Practice Recommendations for Contraceptive Use support initiation of the ENG implant if oral levonorgestrel (LNG) is given concomitantly for EC. This recommendation lacks supporting evidence and serves as a barrier to method initiation, as oral LNG is not typically available in clinics when clients desire an implant. Additionally, oral LNG efficacy decreases in higher body mass index (BMI) users and the role of BMI on efficacy with co-administered oral LNG and the ENG implant is unknown. As the ENG implant is also a synthetic progestogen with a rapid rise and consistent systemic levels, it could plausibly serve as stand-alone EC or increase the efficacy of oral LNG with co-administration. Moreover, the EC mechanism of action, which is related to ovulatory suppression with oral EC, may differ if the implant is initiated with or without oral LNG, impacting efficacy in mid cycle users. This study addresses the following research gaps around use of the ENG implant for EC that serve as barriers to provider comfort with these options: efficacy with and without oral LNG, efficacy differences by BMI, and ovulation frequency with and without oral LNG. The investigators propose a randomized, placebo-controlled, non-inferiority study to determine if the ENG implant alone is no worse than the ENG implant + oral LNG for EC, using a 3.5% non-inferiority margin. The investigators will include clients who present to Planned Parenthood Association of Utah clinics with report of unprotected intercourse within 72 hours who desire EC. Eligible EC clients interested in an implant with a negative pregnancy test will be allocated 1:1 to a study group: (1) ENG implant + oral LNG or (2) ENG implant + placebo. Our experienced research staff will follow up with participants for 4-week efficacy data as primary outcome. Our aims include: (1) To compare the efficacy of the ENG Implant + oral LNG to the ENG Implant + placebo for EC in 790 participants assessed by pregnancy status four weeks after implant placement, (2) To compare pregnancy risk by BMI category (the investigators anticipate half of the 790 participants will have a BMI ≥25) between and within the ENG Implant + oral LNG and the ENG Implant + placebo groups, and (3) To evaluate ovulation frequency within 5 days of insertion of ENG Implant + oral LNG or ENG implant + placebo in 202 participants who are mid cycle (day 7-14 post menses) at time of enrollment assessed by serum progesterone levels and urine fertility monitor results. Our short-term goal is to expand evidence on the efficacy of implant initiation with or without oral LNG to meet the needs of EC clients. Our long-term goals are to develop evidence-based clinical guidelines to inform global contraceptive practices, allow for equity in long acting reversible contraception counseling at the time of EC, and support reproductive autonomy for people to achieve to their life goals.

Official Title
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Generating Evidence to Improve Same-day Etonogestrel (ENG) Implant Insertion for Emergency Contraception

Conditions
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Emergency Contraception

Intervention / Treatment
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* Drug: Etonogestrel implant with Oral Levonorgestrel emergency contraception 1.5mg
* Device: Etonogestrel implant with oral placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unprotected intercourse within 72 hours Biologically capable of pregnancy Fluent in English and/or Spanish Have a regular menstrual cycle (21-35 days) Known last menstrual period (+/- 3 days) Working (cell) phone number Willing to comply with the study requirements Exclusion Criteria: Current pregnancy (+urine pregnancy test in clinic) Breastfeeding Contraindication to ENG or LNG based on CDC Medical Eligibility Criteria Sterilization or has an IUD or contraceptive implant in place Vaginal bleeding of unknown etiology Previous use of EC in same cycle Allergy to LNG or ENG History of intolerance/ side effects with ENG Implant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial of the etonogestrel contraceptive implant randomized to same day oral levonorgestrel or placebo in emergency contraception patients
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Etonogestrel contraceptive implant with oral levonorgestrel<br>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 | Drug: Etonogestrel implant with Oral Levonorgestrel emergency contraception 1.5mg<br>* Single pill of oral levonorgestrel 1.5mg X 1 dose (e.g. Plan B) same day as contraceptive implant insertion<br>|
| Placebo Comparator: Etonogestrel contraceptive implant with placebo<br>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 | Device: Etonogestrel implant with oral placebo<br>* Single pill of placebo same day as contraceptive implant insertion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the etonogestrel contraceptive implant with placebo for emergency contraception | Pregnancy rate = number of pregnancies / participants in the placebo arm | 1 month after enrollment | 
| Efficacy of the etonogestrel contraceptive implant with placebo for emergency contraception by BMI category | Pregnancy rate = # of pregnancies / participants in the placebo arm stratified by BMI category | 1 month after enrollment | 
| Efficacy of the etonogestrel contraceptive implant with oral levonorgestrel for emergency contraception | Pregnancy rate = # of pregnancies / participants in the oral levonorgestrel arm | 1 month after enrollment | 
| Efficacy of the etonogestrel contraceptive implant with oral levonorgestrel for emergency contraception by BMI category | Pregnancy rate = # of pregnancies / participants in the oral levonorgestrel arm stratified by BMI category | 1 month after enrollment | 
| Ovulation frequency within 5 days of implant insertion in the oral levonorgestrel arm | Incidence of ovulation within 5 days after implant insertion measured by urine fertility monitor results and serum progesterone | 5 days after implant insertion | 
| Ovulation frequency within 5 days of implant insertion in the placebo arm | Incidence of ovulation within 5 days after implant insertion measured by urine fertility monitor results and serum progesterone | 5 days after implant insertion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implant continuation | Participants continuing implant use at one month as a proportion of all participants having successful placement of implant at study entry. Measured by probabilities estimated using Kaplan-Meier approach. | 4 weeks after insertion | 
| Implant satisfaction | Likelihood of satisfaction by study group using ordinal regression. Measured by 5-point ordinal scale (5-point ordinal scale: (1) very unsatisfied, (2) unsatisfied, (3) neutral, (4) satisfied, (5) very satisfied). Measured by | 4 weeks after insertion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contraception, etonogestrel implant, oral levonorgestrel