ESI-related Bleeding
Conditions
Keywords
Implanon, Etonogestrel subdermal implant, Nexplanon, Contraception, Irregular Bleeding, Menometrorrhagia
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.
Interventions
DRUGPlacebo
Placebo, one capsule orally twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.
DRUGDoxycycline
Doxycycline 100 mg oral capsules twice daily for 10 days. After 10 days, an additional Secondary treatment may be requested.
Sponsors
Petra M. Casey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 51 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Treatment | After initial treatment up to 39 weeks | The proportion of subjects who requested additional secondary treatment of intervention after ESI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Post ESI Implant - Doxycycline Subjects who were randomization 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 | 42 |
| Post ESI Implant - Placebo Subjects who were randomization 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 | 40 |
| Total | 82 |
Baseline characteristics
| Characteristic | Post ESI Implant - Doxycycline | Post ESI Implant - Placebo | Total |
|---|---|---|---|
| Age, Continuous | 25.6 years STANDARD_DEVIATION 4.7 | 26.0 years STANDARD_DEVIATION 6.9 | 25.8 years STANDARD_DEVIATION 5.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 37 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 39 Participants | 39 Participants | 78 Participants |
| Region of Enrollment United States | 42 participants | 40 participants | 82 participants |
| Sex: Female, Male Female | 42 Participants | 40 Participants | 82 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 40 |
| other Total, other adverse events | 0 / 42 | 0 / 40 |
| serious Total, serious adverse events | 0 / 42 | 0 / 40 |
Outcome results
Primary
Secondary Treatment
The proportion of subjects who requested additional secondary treatment of intervention after ESI
Time frame: After initial treatment up to 39 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post ESI Implant - Doxycycline | Secondary Treatment | 20 Participants |
| Post ESI Implant - Placebo | Secondary Treatment | 23 Participants |
p-value: 0.3795% CI: [-31.4, 11.6]Chi-squared
Secondary
Removal of ESI
Number of subjects who requested ESI removal
Time frame: 26 weeks post-randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post ESI Implant - Doxycycline | Removal of ESI | 4 Participants |
| Post ESI Implant - Placebo | Removal of ESI | 2 Participants |
Secondary
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.
Time frame: 13 weeks post-treatment
Population: In Doxycycline arm 8 subjects were lost to follow up and did not complete any surveys after randomized to treatment. In Placebo arm 7 subjects were lost to follow up and did not complete any surveys after randomized to treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Post ESI Implant - Doxycycline | Subject Satisfaction | 15 Participants |
| Post ESI Implant - Placebo | Subject Satisfaction | 17 Participants |
p-value: 0.46Chi-squared