A Study of Continuous Oral Contraceptives and Doxycycline
Condition: Contraceptives, Oral
Study type: Interventional

Summary: 
      The purpose of this study is to learn if the study drug, doxycycline, can decrease the amount
      of unplanned vaginal bleeding that women commonly experience when taking combined oral
      contraception (COC)- pills with estrogen and progestin - in a continuous fashion - no
      hormone-free week. The study drug, doxycycline, is an antibiotic used commonly for many
      conditions (i.e. acne, Chlamydia infections, pneumonia) and can be safely used on a daily
      basis. Doxycycline has been shown to decrease unplanned vaginal bleeding in progestin-only
      contraception but has not been studied in combined hormonal contraception.
    

Detailed description: 
      We intend to conduct a prospective, randomized, placebo controlled, double blind study at
      Oregon Health and Science University. This study will be conducted over four 28-day cycles
      (112 days of active COC hormone). All women enrolled in the study will take the same daily
      low dose COC. This protocol will be divided into two studies, a bleeding study and an
      endometrial biopsy study, each with two treatment arms; typical dose doxycycline (Arm 1), and
      controlled release subantimicrobial dose doxycycline (CRSD)(Arm 2).

      The first arm (Arm 1) of this study will constitute the typical dose doxycycline arm. In this
      arm, there will be two study groups. Group 1, the treatment group, will take doxycycline 100
      mg orally twice a day for five days starting on the first day of bleeding if breakthrough
      bleeding occurs. The control group will take a placebo orally twice a day for five days
      starting on the first day of bleeding if breakthrough bleeding occurs. After three months,
      both groups will stop doxycycline (or placebo) and will continue on a COC alone for the
      remaining 28 days of the study.

      The second arm (Arm 2) of the study will constitute the controlled release subantimicrobial
      dose doxycycline (CRSD doxycycline)arm. Subjects in this arm of the study will be divided
      into Group 3 and Group 4. Group 3 will take CRSD doxycycline (40mg) daily for three months.
      Group 4 will take a daily placebo. Similarly to the first arm of the trial, after three
      months, both groups will stop doxycycline (or placebo) and will continue in a COC alone for
      the remaining 28 days of the study.

      This study also includes a endometrial biopsy sub-study: At the time of recruitment we will
      identify participants who are willing to undergo endometrial biopsy during the study period.
      These subjects will constitute a separate cohort who will enroll in the prospective,
      randomized, double blind, placebo controlled endometrial biopsy study.
    

Intervention name(s): Lybrel; Doxycycline; Oracea; Placebo; Doxycycline 100bid x5 days at the time of bleeding; Subantimicrobial doxycycline daily; placebo daily
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): All women enrolled in the study will take the same daily low dose oral contraceptive (20-mcg EE/90 mcg LNG) dosed in a continuous fashion.; 100 mg orally twice a day for five days starting on the first day of breakthrough bleeding. This regimen will be repeated if bleeding persists or recurs seven days after completing five-day course of doxycycline.; 40-mg tablet daily for 84 days; Placebo pill orally twice a day for five days starting on the first day of breakthrough bleeding. This regimen will be repeated if bleeding persists or recurs seven days after completing five-day course of placebo; Doxycycline 100 mg orally twice a day for five days starting on the first day of breakthrough bleeding. This regimen will be repeated if bleeding persists or recurs seven days after completing five-day course of doxycycline; Subantimicrobial dose doxycycline 40mg daily for the first 84 days of the study; Placebo daily for the first 84 days of the study
Other intervention name(s): Lybrel (20-mcg Ethinyl Estradiol (EE)/90 mcg Levonorgestrel (LNG)
Intervention MeSH terms: Doxycycline; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: birth control; continuous contraception; break-through bleeding