Does Concomitant Use of Combined Oral Hormonal Steroids Stop Bleeding in Women Using Etonogestrel Implants (Implanon/Nexplanon®)?: A Randomized Controlled Study

Study Overview
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Brief Summary
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The specific aims are to determine if more women using Etonogestrel (ENG) contraceptive implants who report a bleeding-spotting episode of at least seven days will stop bleeding within 3 days of beginning a 14-day course of combined oral hormonal steroids, as compared to women receiving 14 days of placebo.

Detailed Description
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The ENG contraceptive implant (Implanon/Nexplanon®), is a silicone- free, single rod subdermal contraceptive implant that contains 68 mg of etonogestrel, is approved for use for three years, and is one of the most effective forms of contraception available (1). ENG contraceptive implants are easily inserted and removed (1,2), offer quick return to fertility (2), are cost-effective and cost-saving (3,4) and offer non-contraceptive benefits such as improvement in pain for patients with complaints of dysmenorrhea (5). Hypothesis: Women using ENG contraceptive implants who report a bleeding-spotting episode of at least seven days will be more likely to stop bleeding within 3 days of beginning a 14-day course of combined oral hormonal steroids compared to women receiving 14 days of placebo.

Official Title
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Does Concomitant Use of Combined Oral Hormonal Steroids Stop Bleeding in Women Using Etonogestrel Implants (Implanon/Nexplanon®)?: A Randomized Controlled Study

Conditions
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Uterine Hemorrhage, Contraception

Intervention / Treatment
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* Drug: Combined Oral Contraceptive Pill
* Drug: Placebo Sugar Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All female English or Spanish speaking women between the ages of 18-44 using an ENG contraceptive implant who complain of bothersome bleeding and have a current bleeding episode of at least seven days will be invited to participate. Exclusion Criteria: Category 3 or 4 contraindications to estrogen therapy according to the Centers for Disease Control 2010 Medical Eligibility Criteria. Category 3 contraindications: less than 1 month postpartum if breastfeeding, less than 21 days postpartum if not breastfeeding, history of Deep Vein Thrombosis (DVT) /Pulmonary Embolism (PE) not on anticoagulant therapy and no risk factors, Deep venous thrombosis/Pulmonary Embolus on established anticoagulant therapy and no risk factors, history of malabsorptive bariatric surgery, greater than or equal to months post peripartum cardiomyopathy with normal to mildly impaired cardiac function, greater than or equal to 35 years old with less than 15 cigarettes smoked per day, multiple risk factors for arterial cardiovascular disease, adequately controlled hypertension, blood pressure 140-159/90-99 mm Hg, migraines without aura less than 35 years old, past breast cancer and no evidence of recurrent disease for 5 years, diabetes with retinopathy, neuropathy, nephropathy (category 3 or 4 depending on severity), diabetes greater than 20 years duration or associated with other vascular disease, medically treated symptomatic gallbladder disease or current symptomatic gallbladder disease, past combined oral contraceptive pill related cholestasis, acute viral hepatitis, hepatocellular adenoma, hepatoma, use of ritonavir-boosted protease inhibitors, anticonvulsant therapy use including phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, and lamotrigine, use of Rifampicin, Category 4 contraindications: less than 6 months post peripartum cardiomyopathy with normal to mildly impaired cardiac function, any time following peripartum cardiomyopathy with moderately to severely impaired cardiac function, greater than or equal to 35 years old with greater than 15 cigarettes smoked per day, multiple risk factors for arterial cardiovascular disease, blood pressure greater than or equal to 160/100 mm Hg, high risk for recurrent DVT/PE, acute DVT/PE, DVT/PE and on established anticoagulant therapy with greater than or equal to 1 risk factor for recurrent DVT/PE, major surgery/prolonged immobilization, known thrombogenic mutations, current and history of ischemic heart disease, history of stroke, complicated valvular heart disease, systemic lupus erythematosus (SLE) with positive or unknown antiphospholipid antibodies, migraines without aura greater than or equal to 35 years old, migraines with aura at any age, current breast cancer, complicated solid organ transplantation Body mass index (BMI) greater than 35. A systolic blood pressure greater than 135 on more than 2 occasions. assuring the measurements are separated by an interval of at least 15 minutes. A diastolic blood pressure greater than 85 on more than 2 occasions. assuring the measurement are separated by an interval of at least 15 minutes. A positive pregnancy test. A positive chlamydia test. Unable or unwilling to swallow pills. A medical condition deemed severed by a physician investigator. A participant taking a liver enzyme inducing drug. A known allergy to levonorgestrel or ethinyl estradiol. An abnormal speculum exam (i.e. bleeding ectropion or cervical mass). Does not meet appropriate cervical cytology screening guidelines. Cervical procedure done in the past 3 months. On a concurrent hormonal contraceptive and unwilling to discontinue. Breast lesions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sugar Pill<br>Placebo Sugar Pill | Drug: Placebo Sugar Pill<br>* Placebo Sugar Pill<br>|
| Experimental: Combined Oral Contraceptive Pill<br>150 mcg levonorgestrel and 30 mcg ethinyl estradiol combined oral contraceptive pill | Drug: Combined Oral Contraceptive Pill<br>* 150 mcg levonorgestrel and 30 mcg ethinyl estradiol combined oral contraceptive pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cessation of Vaginal Bleeding | Proportion of women in each group who stopped bleeding during therapy and continued to report no bleeding at the end of the 14-day treatment period. | At day 3 of 14 day course of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Days Until Temporary Interruption of Bleeding During Therapy Occurred |  | over the 14 day course of study drug | 
| Number of Days Without Bleeding During Therapy |  | Over the 14 day course of study drug | 
| Number of Days to Recurrence of Bleeding After Discontinuation of Therapy |  | Up to six months |