Treatment of Unacceptable Bleeding Patterns in ETG Implant Users With an Oral Contraceptive (ROBI)

Relief of Bleeding on the Implant: Treatment of Unacceptable Bleeding Patterns in ETG Implant Users With a Combined Oral Contraceptive: A Placebo-Controlled Randomized Trial

This double-blinded, placebo-controlled, randomized trial will compare the effects of the use of a combined oral contraceptive pill to a placebo pill for women who are experiencing irregular and/or heavy bleeding associated with the use of an etonogestrel (ETG) implant.

The hypothesis of the study is:

• Use of combined oral contraceptive will significantly improve bleeding patterns for users of ETG implant
• Continuation rate of ETG implant users will be increased by use of combined oral contraceptive in women desiring ETG implant removal because of the undesirable bleeding
• Adverse events will be uncommon and acceptable to women who use a combined oral contraceptive with the ETG implant

Study Overview

• Status: Terminated
• Conditions: Uterine Bleeding Heavy; Abnormal Uterine Bleeding, Unspecified
• Intervention / Treatment: Drug: EE 30mcg/LNG 150mcg; Drug: Placebo

Detailed Description

Women who are experiencing irregular and/or heavy bleeding associated with the use of an etonogestrel (ETG) implant will be recruited for this study. Women who have bothersome bleeding will be randomized to use either a combined oral contraceptive pill or a placebo pill.

Participants will take one pill every day and record their bleeding patterns on a daily diary.

Participants will have one screening/enrollment visit, two in-person follow up visits, and one telephone follow up contact. Subjects will be enrolled for a total of 84 days (three months).

Participants will be assigned to a treatment group at her screening/enrollment visit. Her first follow up visit will occur 22-28 days after her enrollment. Participants can choose to:

• Continue use of assigned treatment medication
• Discontinue use of assigned treatment medication, but use an open-label combined oral contraceptive pill
• Discontinue the use of assigned treatment medication, decline use of an open-label combined oral contraceptive pill
• Discontinue use of ETG implant.

Participants who choose to continue use of ETG implant will have a follow up telephone contact 50-56 days after her enrollment visit. A final in-person visit will occur 78-84 days after enrollment. Bleeding patterns will be assessed by daily bleeding diaries completed by the participant.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California, Davis Department of Obstetrics and Gynecology
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Department of Obstetrics and Gynecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women who have an ETG implant in place
• Women who subjectively experience the side effect of an undesirable bleeding profile such as bleeding irregularity or heavy flow after ETG implant was placed and who desire intervention for this side effect by either treatment of bleeding or removal of the implant
• Age 14 years an older, inclusive

Exclusion Criteria:

• Irregular or heavy bleeding from an etiology other than ETG use (e.g. fibroids, cervical polyp, or other organic cause of bleeding)
• Has attempted prescription treatment for menstrual side effects while using ETG implant

• Has one or more of the conditions considered Category 3 (risks outweigh benefits) or Category 4 (unacceptable health risk) for estrogen-containing oral contraceptives by the Center for Disease Control Medical Eligibility Criteria for Contraceptive Use:

  • Current or history of heart or vascular diseases, including deep venous thrombosis, pulmonary embolism, known thrombogenic mutations, peripartum cardiomyopathy, and complicated valvular heart disease
  • Hypertension, even if adequately controlled
  • Diabetes with vascular involvement
  • Headaches with focal aura, or migraines in women age 35 and older even without focal aura
  • Major surgery with prolonged immobilization
  • Breast cancer (current or past)
  • Severe (decompensated) cirrhosis
  • Acute or flare viral hepatitis
  • Breastfeeding less than 1 month postpartum
  • Post-partum less than 3 weeks
  • 35 years of age and older and smoking
  • Multiple risk factors for arterial cardiovascular disease
  • Systemic Lupus Erythematosus with positive or unknown antiphospholipid antibodies
  • Current symptomatic gallbladder disease or history of cholestasis related to past combined oral contraceptive use
  • On certain anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine, lamotrigine)
  • On Ritonavir-boosted protease inhibitors for antiretroviral therapy
• Issues or concerns, in the judgment of the investigator, that may compromise the safety of the subject, impact the subject's adherence to the protocol requirements, or confound the reliability of the data acquired in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1 pill per day; daily during study participation (up to 84 days)
Active Comparator: EE 30mcg/LNG 150mcg; combined oral contraceptive pill: ethinyl estradiol (EE) 30mcg/levonorgestrel 150mcg); 1 pill per day; daily during study participation (up to 84 days)	Drug: EE 30mcg/LNG 150mcg; 1 pill per day; daily during study participation (up to 84 days); Other Names: Levora; Portia 28; Levlen28; Altavera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Bleeding Improvement	Bleeding improvement will be measured by participant response to the question of whether she feels her bleeding is improved and she is satisfied with the treatment.	Bleeding improvement will be evaluated during first cycle of study treatment (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Participants will be evaluated for adverse events while using a combined oral contraceptive with ETG implant.	Adverse events will be evaluated at each contact (visits at 1 and 3 months, phone contact at 2 months) with the participant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants withTreatment Success or Failure	Treatment success will be measured by desire to continue treatment because the initial treatment made the bleeding better. Partial failure of the study treatment will be measured by the desire to continue treatment because the initial treatment did not work Complete failure of treatment will be measured by the desire to: discontinue treatment because it did not work; no further treatment requested; ETG implant removal; Desire to use non-study treatment	Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months
Bleeding Patterns and Number of Participants With Bleeding Improvement	Bleeding improvement in women who received placebo but opted for open-label treatment after first cycle; Bleeding improvement over the 84 days of study participation; Bleeding patterns in placebo vs. combined oral contraceptive users	Evaluated at follow up visits at 1 month and, if subject continues after 1st month, again at 3 months

Collaborators and Investigators

• Sponsor: University of California, Davis
• Collaborators: Washington University School of Medicine
• Investigators: Principal Investigator: Mitchell Creinin, MD, University of California, Davis; Study Director: Melody Hou, MD, University of California, Davis

Publications and helpful links

General Publications

• Hou MY, McNicholas C, Creinin MD. Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomised controlled trial. Eur J Contracept Reprod Health Care. 2016 Oct;21(5):361-6. doi: 10.1080/13625187.2016.1210122. Epub 2016 Jul 15.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: October 10, 2013
• First Submitted That Met QC Criteria: October 11, 2013
• First Posted (Estimate): October 16, 2013

Study Record Updates

• Last Update Posted (Actual): May 12, 2017
• Last Update Submitted That Met QC Criteria: April 4, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: birth control; etonogestrel implant; irregular bleeding; heavy bleeding
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Hemorrhage; Uterine Hemorrhage
• Other Study ID Numbers: 478388; MISP 50618 (Other Grant/Funding Number: Merck Sharp & Dohme Corp.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO