A Study of Continuous Oral Contraceptives and Doxycycline - Full Text View

Sponsor:	Oregon Health and Science University
Collaborator:	OHSU Family Planning Fellowship Foundation
Information provided by (Responsible Party):	Jeffrey Jensen, Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00480532

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 (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
Menstrual Bleeding	Drug: Lybrel Drug: Doxycycline Drug: Oracea Drug: Placebo

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

Resource links provided by NLM:

MedlinePlus related topics: Birth Control

Drug Information available for: Doxycycline Doxycycline hyclate Doxycycline calcium

U.S. FDA Resources

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

Primary Outcome Measures:

Differences in bleeding patterns between study groups. [ Time Frame: Per 28 day cycle, and for the entire 84 day treatment phase, and 28 day post treatment phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Subject satisfaction. [ Time Frame: At enrollment and after the 3rd cycle of participation, and at the end of study (4th 28 day cycle) ] [ Designated as safety issue: No ]
Subject compliance [ Time Frame: Per 28 day cycle and for the entire 84 day treatment phase, and 28 day post treatment phase ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
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: 1	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. 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.
Placebo Comparator: 2	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. 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: 3	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. Drug: Oracea 40-mg tablet daily for 84 days
Placebo Comparator: 4	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. 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

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 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 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:

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

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

Locations

United States, Hawaii
University of Hawaii
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

OHSU Family Planning Fellowship Foundation

Investigators

Principal Investigator:

Jeffrey T Jensen, M.D, MPH

Oregon Health and Science University

More Information

Additional Information:

Women's Health Research Unit website This link exits the ClinicalTrials.gov site

No publications provided by Oregon Health and Science University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kaneshiro B, Edelman A, Carlson N, Morgan K, Nichols M, Jensen J. Treatment of unscheduled bleeding in continuous oral contraceptive users with doxycycline: a randomized controlled trial. Obstet Gynecol. 2010 Jun;115(6):1141-9.

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
Last Updated:	February 9, 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:

Hemorrhage
Pathologic Processes
Contraceptive Agents
Contraceptives, Oral
Doxycycline
Doxycycline hyclate
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

ClinicalTrials.gov processed this record on February 13, 2012