A Study of Continuous Oral Contraceptives and Doxycycline

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jeffrey Jensen, Oregon Health and Science University
ClinicalTrials.gov Identifier:
NCT00480532
First received: May 30, 2007
Last updated: December 17, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention
Contraceptives, Oral
Drug: Lybrel
Drug: Doxycycline
Drug: Oracea
Drug: Placebo
Drug: Doxycycline 100bid x5 days at the time of bleeding
Drug: Subantimicrobial doxycycline daily
Drug: placebo daily

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Study of Continuous Oral Contraceptives and Doxycycline

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Differences in Bleeding Patterns Between Study Groups. [ Time Frame: The outcome was also assessed for day 1 to 84 ] [ Designated as safety issue: No ]
    number of days of bleeding and spotting, self reported on calendar


Secondary Outcome Measures:
  • Subject Satisfaction. [ Time Frame: Assessed on day 112 of the study (the end of the study period). This outcome does not represent a change from baseline. It was assessed at the end of the study period. ] [ Designated as safety issue: No ]
    measured using 100 mm visual analog scale. anchors of "not at all satisfied" (0mm) "extremely satisfied" (100mm)

  • Subject Compliance [ Time Frame: Assessed on day 112 of the study (the end of the study period). The outcome reflects the number of subjects who did not miss pills during the entire 112 day study. It does not represent a change from baseline. ] [ Designated as safety issue: No ]
    measured by self report of pill intake on daily diary (yes/no), and reported as percentage with no missed pills over entire study


Enrollment: 131
Study Start Date: May 2007
Study Completion Date: May 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxycycline 100bid x5 days Drug: Lybrel
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.
Other Name: Lybrel (20-mcg Ethinyl Estradiol (EE)/90 mcg Levonorgestrel (LNG)
Drug: 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.
Drug: Doxycycline 100bid x5 days at the time of bleeding
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
Placebo Comparator: placebo bid x 5 days Drug: Lybrel
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.
Other Name: Lybrel (20-mcg Ethinyl Estradiol (EE)/90 mcg Levonorgestrel (LNG)
Drug: Placebo
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
Experimental: Subantimicrobial doxycycline daily Drug: Oracea
40-mg tablet daily for 84 days
Drug: Subantimicrobial doxycycline daily
Subantimicrobial dose doxycycline 40mg daily for the first 84 days of the study
Placebo Comparator: placebo daily Drug: placebo daily
Placebo daily for the first 84 days of the study

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General good health
  • Willing and able to agree to randomization and sign informed consent
  • Currently having regular menstrual cycles (24-36 days), with combined cyclic hormonal method (COCs, Nuva Ring, Ortho Evra), without intermenstrual bleeding in last 2 years.

Exclusion Criteria:

  • Intrauterine device (IUD) in place
  • Abnormal pap smear that has not been treated or followed up
  • Those with hypersensitivity reactions to doxycycline or any of the tetracyclines
  • Use of depomedroxyprogesterone acetate within 9 months of the start of the study.
  • Use of hormonal medications (excluding cyclic contraceptives and plan B) within 2 months of the start of the study.
  • Any one unwilling to keep a daily menstrual diary or otherwise unwilling to follow the study criteria
  • Currently taking medications that interfere with COCs (rifampin, carbamazepine, St. Johns wort)
  • Currently has a progestin implant
  • Positive Gonorrhea or Chlamydia cultures at enrollment examination
  • Smoking more than 5 cigarettes per month
  • Any medical condition that is a contraindication to the use of COCs in accordance with product labeling including:

    • History of thrombophlebitis, deep venous thrombosis, thrombogenic vasculopathies, thrombogenic rhythm disorders or thromboembolic disorders
    • Current or past history of cerebrovascular or coronary artery disease
    • Scheduled major surgery in the next six months with prolonged immobilization
    • Diabetes with vascular involvement
    • Headache with focal neurologic symptoms
    • Uncontrolled hypertension
    • Suspected or known carcinoma of the breast or personal history of breast cancer
    • Carcinoma of the endometrium or other known or suspected estrogen dependent neoplasms
    • Undiagnosed genital bleeding
    • History of cholestatic jaundice of pregnancy or cholestatic jaundice with prior oral contraceptive use
    • Hepatic adenoma or carcinoma or active liver disease if liver function has not returned to normal
    • Known or suspected pregnancy
    • Hypersensitivity to estrogen or progesterone containing products
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00480532

Locations
United States, Hawaii
University of Hawaii (UH)
Honolulu, Hawaii, United States, 26826
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
Sponsors and Collaborators
Oregon Health and Science University
Investigators
Principal Investigator: Jeffrey T Jensen, M.D, MPH Oregon Health and Science University
  More Information

Publications:
Responsible Party: Jeffrey Jensen, MD MPH, Oregon Health and Science University
ClinicalTrials.gov Identifier: NCT00480532     History of Changes
Other Study ID Numbers: OHSU FAMPLAN 2907
Study First Received: May 30, 2007
Results First Received: May 21, 2012
Last Updated: December 17, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Oregon Health and Science University:
birth control
continuous contraception
break-through bleeding

Additional relevant MeSH terms:
Contraceptive Agents
Levonorgestrel
Ethinyl estradiol, levonorgestrel drug combination
Contraceptives, Oral
Doxycycline
Ethinyl Estradiol
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Contraceptive Agents, Female
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Contraceptives, Oral, Synthetic
Contraceptives, Oral, Combined

ClinicalTrials.gov processed this record on August 26, 2014