CCTN Vaginal Ring

Principal Investigator: David Turok
Keywords: Family Planning , Contraception , Birth Control Department: DFPM-Family Practice
IRB Number: 00086673 Co Investigator: Lori Gawron
Specialty: OB/Gyn, General
Sub Specialties: Women's Health
Recruitment Status: Completed

Contact Information

Amy  Orr
amy.orr@hsc.utah.edu
801-213-2774

Brief Summary

Primary Objective:  

To evaluate one-month data on the serum estradiol (E2) levels of three different contraceptive vaginal rings containing a fixed dose of Nestorone (NES) and one of three selected doses of E2.   Serum estradiol levels will serve as the basis for selecting a contraceptive vaginal ring (CVR) dose for a contraceptive efficacy trial.

Secondary Objectives:

To evaluate the effects of three different doses of estradiol in a NES- E2 CVR on progesterone levels, bleeding satisfaction and side effects during one month of use. Nestorone serum levels will be measured as an indication of compliance with the continuous use of the ring.  The pattern of bleeding associated with a hormone-free interval (HFI) will be evaluated in an optional extension study where subjects will continue with the same ring for an additional 60 days.  Subjects in the extension study will remove the ring for either 2 or 4 days at d30, and d60.  Subjects will be randomized to either the same 2 or 4 day schedule to be used with each ring removal. 

Inclusion Criteria

Women who meet all the following criteria are eligible for enrollment in the trial:

  1. Good general overall health with no chronic medical conditions that result in periodic exacerbations that require significant medical care.

  2. Age 18-39 years, inclusive, at the enrollment visit.

  3. Have a regular menstrual cycle 21-35 days in duration when not using hormonal contraception.

  4. Have an intact uterus and both ovaries.

  5. Able and willing to comply with the protocol and sign an informed consent.

  6. Consistent use of contraception during the preceding cycle (note:women who use oral, transdermal, vaginal, implantable or intrauterine hormonal contraceptives in the preceding cycle must have discontinued at least 7 days prior to start of treatment and not had unprotected intercourse since discontinuing the method).

  7. Not at high risk for pregnancy, defined as consistently using a non-hormonal contraception, have a surgically sterile male partner with a vasectomy; be abstinent, or be in a same-sex relationship from the start of treatment through study exit (including recovery period).

  8. Have a negative pregnancy test at the admission visit.

  9. Have a diastolic blood pressure (BP) ≤85 mm Hg and systolic BP ≤135 mm Hg after 5 minutes in sitting position at the admission visit.

  10. Willing to abstain from use of non-water based vaginal lubricant during the study.

     

Exclusion Criteria

Women who meet any of the following criteria are not eligible for enrollment in the trial:

  1. Participating in another clinical trial involving an investigational product within the last 30 days (prior to screening) or planning to participate in another clinical trial during this study.
  2. Not living in the catchment area of the study site.
  3. Known hypersensitivity to progestins or estrogen.
  4. All contraindications to combined estrogen-progestin contraceptive use including:
    • Thrombophlebitis or thromboembolic disorders.

    • Past personal history of deep vein thrombophlebitis or thromboembolic disorders.

    • History of venous thrombosis or embolism in a first-degree relative <55 years of age suggesting familial defect in blood coagulation system,

    • History of thrombosis or embolism OR any other personal or family history which in the opinion of the investigator suggests increased risk.

    • History of stroke.

    • Known or suspected carcinoma of the breast.

    • Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia.

    • Undiagnosed abnormal genital bleeding.

    • Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use.

    • Hepatic adenomas or carcinomas.

    • Known or suspected pregnancy.

    • Smoking in women who are 35 years and over or will be 35 years during the course of the trial; women <35 years who smoke 15 cigarettes or more per day must be evaluated by the investigator for inclusion based on risk factors that would increase their risk for cardiovascular disease (CVD) and thromboembolism, e.g. lipid levels, glucose level, BP, BMI, family history of CVD at a young age.

    • History of retinal vascular lesions, unexplained partial or complete loss of vision.

    • Headaches with focal neurological symptoms (e.g., migraines with auras).

  1. Desire to become pregnant during the study.
  2. Breastfeeding.
  3. Undiagnosed vaginal discharge or vaginal lesions or abnormalities.  Subjects diagnosed at screening with a Chlamydia or gonococcus infection may be included in the trial following treatment; partner treatment is also recommended. Subjects with vaginal infection (yeast, trichomonis, or bacterial vaginosis) may be enrolled after treatment.  Investigators should make a determination if subjects are at high risk for reinfection, e.g. multiple sex partners, untreated partner, and whether such subjects can be included. In accordance with PI/medical designee assessment and local standards of practice, women with a history of genital herpes can be included if outbreaks are infrequent.
  4. A known clinically significant Pap test abnormality, as managed by current local or national guidelines that will require treatment during study participation. 
  5. Known benign or malignant liver tumors; known active liver disease.

  1. Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin cancer).
  2. Current or past medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive.
  3. Known or suspected current alcoholism or drug abuse.
  4. Elevated serum fasting clinical chemistry values or complete blood count (CBC) values designated clinically significant by the investigator or medically qualified sub-investigator.
  5. Uncontrolled thyroid disease.
  6. Known impaired hypothalamic-pituitary-adrenal reserve.
  7. Body mass index (BMI) >35.
  8. Use of injectable contraceptives (e.g. cyclofem or depo-medroxyprogesterone acetate) during the 9 months prior to enrollment or no spontaneous menses since last injection. 
  9. Use of oral, transdermal, vaginal, implantable or intrauterine contraceptives within 7 days prior to start of the treatment cycle. (Copper IUD is not allowed.  Levonorgestrel IUD is not allowed.)  NOTE: Discontinuation of any of these methods must have been for personal reasons unrelated to the purpose of enrollment in this study.
  10. Known hypersensitivity to silicone rubber.
  11. History of toxic shock syndrome.
  12. Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a vaginal ring.
  13. Planning to undergo major surgery during study participation.
  14. Severe constipation.
  15. Use of liver enzyme inducers or inhibitors on a regular basis.
  16. Known HIV infection.
  17. Bariatric surgery within the past year prior to enrollment.
  18. Have issues or concerns (in the judgment of the investigator) that may compromise the safety of the subject or confound the reliability of compliance and information acquired in this study.

Use of the following medications will result in exclusion from the study:

  • Isotretinoin

  • Any sex steroid hormonal treatments (androgens, estrogens, progestins)

  • Vaginal treatment for inter-current illness.Oral medication should be used rather than a vaginal treatment.

  • Anticonvulsant therapies (phenytoin, phenobarbital, carbamazepine, oxcarbazepine, levetiracetam, felbamate, topiramate excluding Valproic Acid)Use of CYP3a4 liver enzyme-inducing or inhibiting medications on a regular basis

    • Rifampicin, dexamethasone, griseofluvin, retinoic acid, ketoconazole

    • St. John's Wort

Additional details about excluded medications are included in Appendix 2.

A subject with recent use of an exclusionary medication may participate if she has discontinued use of the drug at least 30 days prior to the screening visit.  The reason for discontinuation of the medication must not be solely for participation in the study.  All concomitant treatments will be recorded in the subject’s medical records, including the generic name of the drug, regimen, route of administration, start and stop dates, and reason for use.  Any other investigational medication should be stopped 30 days before the start of the present study.  Other prescriptions for the treatment of inter-current medical conditions should be permitted and recorded as detailed above.

Vaginal lubricants containing mineral oil and other oil-based vaginal products may interfere with the absorption of the steroid, and should not be used while the CVR is in place during the study (any prohibited use will be recorded).  Silicone based lubricants will cause the ring to expand and must not be used.  Water-based vaginal lubricants, such as K-Y Jelly and Replens, are permitted.  Tampons may be used (care in removal is required when concurrently used with the CVR to prevent ring expulsion).  Treatment for vaginal yeast infections should be oral or cream and no miconazole suppositories should be used.