Management of Etonogestrel Subdermal Implant-related Bleeding

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

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.

Study Overview

• Status: Completed
• Conditions: ESI-related Bleeding
• Intervention / Treatment: Drug: Doxycycline; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Post ESI implant - 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	Drug: Doxycycline; Doxycycline 100 mg oral capsules twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.; 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; 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; Placebo, one capsule orally twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.; Other Names: Sugar pill

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Petra M. Casey
• Investigators: Principal Investigator: Petra Casey, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2012
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): December 30, 2019

Study Registration Dates

• First Submitted: August 2, 2012
• First Submitted That Met QC Criteria: August 3, 2012
• First Posted (Estimate): August 7, 2012

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Contraception; Implanon; Nexplanon; Irregular Bleeding; Etonogestrel subdermal implant; Menometrorrhagia
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: 11-008933

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No