Management of Etonogestrel Subdermal Implant-related Bleeding

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01658995
Recruitment Status : Recruiting
First Posted : August 7, 2012
Last Update Posted : October 25, 2016
Information provided by (Responsible Party):
Petra M. Casey, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
ESI-related Bleeding Drug: Doxycycline Drug: Placebo Phase 3

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  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Management of Etonogestrel Subdermal Implant-related Bleeding in US Women: a Prospective, Randomized, Placebo-controlled Trial.
Study Start Date : August 2012
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Doxycycline
Doxycycline 100 mg oral capsules, twice daily for 10 days
Drug: Doxycycline
Doxycycline 100 mg oral capsules twice daily for 10 days
Other Name: Adoxa, Alodox, Avidoxy, Bio-Tab, Doryx, Doxy Lemmon, Doxy-Caps, Monodox, Morgidox, Ocudox, Oracea, Oraxyl, Periostat, Vibra-Tabs, Vibramycin
Placebo Comparator: Placebo
Placebo capsules, identical to oral Doxycycline 100 mg, twice daily for 10 days.
Drug: Placebo
Placebo, one capsule orally twice daily for 10 days
Other Name: Sugar pill

Primary Outcome Measures :
  1. Efficacy and safety of Doxycycline compared to placebo for unacceptable bleeding [ Time Frame: 13 weeks post-randomization ]

    The efficacy of Doxycycline on ESI-related bleeding will be compared to placebo based on rates of unacceptable bleeding and weekly prospective symptom diary at 13 weeks post-randomization.

    Method continuation rate at 13 weeks post-randomization will be compared.

    Bleeding patterns will be quantified based on the PBLAC and WHO classification of clinically important bleeding patterns over each 13 week reference period.

    Incidence of additional symptoms including acne, headache, mood changes in the treatment groups will be compared to placebo at randomization and 13 weeks post-randomization based on the weekly prospective symptom diary.

    Interval to recurrence of unacceptable bleeding post-randomized treatment will be calculated.

    Rate of adverse events associated with medical treatment will be documented by prospective symptom diary and BMI calculation. These include headache, mood changes, acne and change in BMI.

Secondary Outcome Measures :
  1. Patient Satisfaction [ Time Frame: Change from randomization to 13 weeks post-treatment ]

    Patient satisfaction with ESI will be assessed at randomization (pre-treatment)and will be compared to patient satisfaction assessed at 13 weeks following primary treatment with Doxycycline / placebo.

    For patients receiving secondary treatment with Doxycycline, satisfaction with ESI will be assessed again at 26 weeks post-randomized treatment.

  2. Method Continuation rate [ Time Frame: 26 weeks post-randomization ]

    Method continuation rate at 26 weeks post-randomized treatment for patients with continued unacceptable bleeding after primary treatment who undergo secondary treatment with Doxycycline will be calculated Rate of ESI removal for bleeding between 13 and 26 weeks post randomization. Rate of ESI removal for reasons other than bleeding with enumeration of reasons for removal between 13 and 26 weeks post-randomization.

    Alternative contraception chosen in the event of ESI removal will be documented.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 51 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01658995

Contact: Amanda L Severson 507-293-3446
Contact: Maureen A Lemens, BSN, RN 507-293-1487

United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Amanda L Severson    507-293-3446   
Contact: Maureen A Lemens, BSN, RN    507-293-1487   
Sponsors and Collaborators
Petra M. Casey
Principal Investigator: Petra Casey, MD Mayo Clinic

Responsible Party: Petra M. Casey, Associate Professor of Obstetrics - Gynecology, Mayo Clinic Identifier: NCT01658995     History of Changes
Other Study ID Numbers: 11-008933
First Posted: August 7, 2012    Key Record Dates
Last Update Posted: October 25, 2016
Last Verified: October 2016

Keywords provided by Petra M. Casey, Mayo Clinic:
Etonogestrel subdermal implant
Irregular Bleeding

Additional relevant MeSH terms:
Pathologic Processes
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs