Management of Etonogestrel Subdermal Implant-related Bleeding

Phase 3

Completed

Conditions: ESI-related Bleeding

Interventions: Drug: Placebo
Drug: Doxycycline

Registration Number: NCT01658995

Lead Sponsor: Petra M. Casey

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 82

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Post ESI implant - Placebo	Placebo	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
Post ESI implant - Doxycycline	Doxycycline	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

Primary Outcome Measures

Name	Time	Method
Secondary Treatment	After initial treatment up to 39 weeks	The proportion of subjects who requested additional secondary treatment of intervention after ESI

Secondary Outcome Measures

Name	Time	Method
Subject Satisfaction	13 weeks post-treatment	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."
Removal of ESI	26 weeks post-randomization	Number of subjects who requested ESI removal