Clinical trial: Dose Finding Study of Contraceptive Vaginal Ring With Different Estradiol Levels in Combination With Nestorone (NCT02626208)

Eligibility criteria:
Inclusion Criteria:

          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 effective 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 method of
             contraception (including Copper IUDs); 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 rest in sitting position at the admission visit.

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

        Exclusion Criteria:

          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. 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).

          5. Desire to become pregnant during the study.

          6. Breastfeeding.

          7. 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.

          8. A known clinically significant Pap test abnormality, as managed by current local or
             national guidelines that will require treatment during study participation.

          9. Known benign or malignant liver tumors; known active liver disease.

         10. Invasive cancer (past history of any carcinoma or sarcoma, except non-melanoma skin
             cancer).

         11. Current or past medically diagnosed severe depression, which, in the opinion of the
             investigator, could be exacerbated by use of a hormonal contraceptive.

         12. Known or suspected current alcoholism or drug abuse.

         13. Elevated serum fasting clinical chemistry values or complete blood count (CBC) values
             designated clinically significant by the investigator or medically qualified
             sub-investigator.

         14. Uncontrolled thyroid disease.

         15. Known impaired hypothalamic-pituitary-adrenal reserve.

         16. Body mass index (BMI) >35.

         17. 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.

         18. Use of oral, transdermal, vaginal, implantable or intrauterine contraceptives within 7
             days prior to start of the treatment cycle. (Copper IUD is allowable. Levonorgestrel
             releasing 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.

         19. Known hypersensitivity to silicone rubber.

         20. History of toxic shock syndrome.

         21. Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a
             vaginal ring.

         22. Planning to undergo major surgery during study participation.

         23. Severe constipation.

         24. Use of liver enzyme inducers or inhibitors on a regular basis.

         25. Known HIV infection.

         26. Bariatric surgery within the past year prior to enrollment. 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.
Female
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 39 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction