Management of Etonogestrel Subdermal Implant-related Bleeding

Study Overview
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Brief Summary
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This is a double-blinded, randomized, prospective placebo-controlled clinical trial to be conducted within the Mayo Clinic and the Mayo Clinic Health System. The goal of the research study is to gather information to determine whether Doxycycline is effective for the treatment of unacceptable bleeding associated with the etonogestrel subdermal implant (ESI), as compared to placebo.

Detailed Description
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ESI is a long-acting reversible contraceptive. Though safety and efficacy have been established world wide, only about 1 % of women have been reported to use this method. Its use is limited by bleeding pattern changes which result in requests for early removal, most commonly within the first 8 months of use. Women ages 18-51 years, choosing ESI and who meet eligibility criteria, will be offered enrollment in the study at the time of ESI insertion. Every effort will be made to insert Implanon on the same day as consent unless medically contraindicated. Prospective diaries will be completed starting on the date of ESI insertion. All participants will be contacted by study personnel 13 weeks after enrollment and queried as to the presence of unacceptable bleeding. Bleeding concerns will be objectively assessed using a modification of the Pictorial Blood Loss Assessment Chart (PBLAC). Participants initiating contact with bleeding concerns at any time after 13 weeks post-ESI insertion will be offered treatment randomization at the time of contact. The basis for randomized treatment will be whether the bleeding is considered unacceptable to the participant. This is inherently subjective, but constitutes the basis for most removal requests. Participants that report unacceptable bleeding at 13 weeks post-ESI insertion, and those who call with bleeding concerns anytime after 13 weeks post-ESI insertion, will be randomized into one of two groups, Doxycycline or matching placebo. Participants that do not report unacceptable bleeding will continue to complete diaries and may be eligible for randomized treatment if unacceptable bleeding develops.

Official Title
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Management of Etonogestrel Subdermal Implant-related Bleeding in US Women: a Prospective, Randomized, Placebo-controlled Trial.

Conditions
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ESI-related Bleeding

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premenopausal women, aged 18-51 years Expressed desire for compliance-independent contraception No current pregnancy or anticipated desire for childbearing within 3 years of study enrollment and Implanon insertion Agreement to participate in all study related procedures and evaluations as documented by a signed informed consent Exclusion Criteria: Current or prior use of Implanon Current long-term use of Doxycycline for other indications Known structural uterine abnormalities such as polyp, submucosal leiomyoma Prior permanent sterilization or endometrial ablation Pregnancy or desire for childbearing within 3 years Contraindications to or intolerance of etonogestrel Allergy to or intolerance of Doxycycline Inability or unwillingness to complete study related procedures and evaluations

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 51 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Post ESI implant - Doxycycline<br>Subjects will be randomized into this arm after experiencing dissatisfaction with bleeding after 13 weeks post ESI insertion and received Doxycycline 100 mg oral capsules, twice daily for 10 days. After 10 days, subsequent treatment can requested by the subjects | Drug: Doxycycline<br>* Doxycycline 100 mg oral capsules twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.<br>* Other names: Adoxa, Alodox, Avidoxy, Bio-Tab, Doryx, Doxy Lemmon, Doxy-Caps, Monodox, Morgidox, Ocudox, Oracea, Oraxyl, Periostat, Vibra-Tabs, Vibramycin;|
| Placebo Comparator: Post ESI implant - Placebo<br>Subjects will be randomized into this arm after experiencing dissatisfaction with bleeding after 13 weeks post ESI insertion and received placebo 100 mg oral capsules, twice daily for 10 days. After 10 days, subsequent treatment can requested by the subjects | Drug: Placebo<br>* Placebo, one capsule orally twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Treatment | The proportion of subjects who requested additional secondary treatment of intervention after ESI | After initial treatment up to 39 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Satisfaction | Number of subjects who reported satisfaction with bleeding after 13 weeks post ESI insertion. As measured by the number of subjects answering very satisfied or satisfied on the Patient Satisfaction Survey question To what extent have you been satisfied overall while using the contraceptive implant? Very satisfied, satisfied, neither satisfied or dissatisfied, dissatisfied or very dissatisfied. | 13 weeks post-treatment | 
| Removal of ESI | Number of subjects who requested ESI removal | 26 weeks post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implanon, Etonogestrel subdermal implant, Nexplanon, Contraception, Irregular Bleeding, Menometrorrhagia