Official Title: “Treatment of Menorrhagia in Women With Aplastic Anemia: Platelet Transfusion Alone to Platelet Transfusion With Continuous Oral Contraceptive Pills”

This study will explore the role of oral contraceptive pills in managing uterine bleeding in women who have low blood platelet counts as a result of aplastic anemia. Oral contraceptive pills have been shown to be effective in managing uterine bleeding in healthy women, but the effects have not been thoroughly studied in women who have low platelet counts. The purpose of the study is to determine whether oral contraceptive pills are a useful complement to platelet transfusions in women with aplastic anemia and uterine bleeding.

Volunteers for this study must be women between 12 and 55 years of age who have been diagnosed with aplastic anemia (with a platelet count of less than 50,000/microl) and currently have active uterine bleeding. Candidates must not be pregnant or breastfeeding, must have a uterus and at least one functioning ovary, and must be willing to use nonhormonal methods of birth control (such as condoms or a diaphragm) for the duration of the study. On the first visit, candidates will be screened with a complete medical history (including obstetric and gynecological history) and will undergo a physical examination, a pelvic exam and a pelvic ultrasound. Blood and urine samples will also be taken on this first visit.

The study will last approximately two weeks. Participants will be asked to monitor their medication doses and severity of bleeding during the course of the study. After the first visit, participants will be separated into two randomized groups and will receive either one tablet of oral contraceptive or a placebo twice daily, to be taken 12 hours apart at the same times each day. Participants will also receive platelet transfusions as needed to ensure that their platelet counts remain over 20,000/microl. After seven days, researchers will assess participants' uterine bleeding and all participants will be given oral contraceptives in the second week of the study. Participants whose bleeding has decreased will receive only one tablet; participants who still have moderate to severe uterine bleeding will receive two tablets. A final assessment will be performed on day 14 of the study.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2010

Low platelet counts can occur as a result of blood diseases like aplastic anemia or chemotherapy treatment. A major complication of low platelet counts in reproductive aged women is uterine bleeding, which can be life threatening. Sometimes this bleeding begins with a normal menstrual cycle but may start unexpectedly. In either instance, stopping uterine bleeding not only requires blood products including platelets but also hormonal treatments.

The hormones estrogen or progesterone can aid in this setting presumably by promoting endometrial angiogenesis. Continuous oral contraceptive pills (OCP) have been shown to be very effective in the management of heavy menstrual bleeding in healthy women, but few studies have been carried out in women with low platelet counts. Moreover, they have few side-effects and are contraceptive. High-dose intravenous Premarin is also useful but only for a couple of days after which heavy bleeding will ensue. Progestin hormones are similarly effective and are also contraceptive.

Oral contraceptive pills are routinely used to control uterine bleeding in aplastic women during episodes of severe thrombocytopenia. There are no current data supporting whether the use of hormonal management is necessary in addition to platelet transfusion. We expect to show that using continuous OCP in addition to having platelet transfusions will result in a better and more rapid control of uterine bleeding than having platelet transfusions only.

Eligible subjects will be menstruating women aged 12-55, who have aplastic anemia with platelet levels less than 50,000 microliters and present with heavy menstrual bleeding.

Subjects will be randomized to either continuous OCP (Lo-ovral) 1 tablet twice daily or placebo twice daily for one week.

All subjects will receive platelet transfusions to keep platelet levels above 20,000 microliters throughout the study. After one week, all subjects who continue to bleed will receive continuous OCP 1 tablet twice daily. Those who have stopped bleeding will receive continuous OCP 1 tablet daily.

Treatments will be compared for the proportion who stop vaginal bleeding 7 and 14 days after starting treatment.

Intervention(s) in this Clinical Trial

• Drug: Lo-Ovral Oral Contraceptive Pills
  • N/A

Primary Measures

• Stop vaginal bleeding or spotting.
  • Time Frame: 1 week
    Safety Issue?: No

Secondary Measures

• Proportion who stop uterine bleeding by day 14. Total number of bleeding days during the first 7 days. Number of days after starting treatment until bleeding stops or spotting. Amount of unterine bleeding. Total number units of PRBC and platelets.
  • Time Frame: 2 weeks
    Safety Issue?: No

INCLUSION CRITERIA:

• Women aged 12-55 years who have a uterus and at least one functioning ovary.
• Women with any active uterine bleeding more than spotting
• Diagnosed with aplastic anemia with platelet counts less than 50,000 microliters at study entry
• Do not desire pregnancy for the duration of the study.
• Willing and able to give informed consent.
• Willing and able to comply with study requirements.

EXCLUSION CRITERIA:

• Age less than 12 years
• Postmenopausal women
• Hormone level in menopausal range: FSH greater than 40 IU/L, E (2) less than 20 pg/ml
• History of liver disease that precludes OCP use
• History of thrombosis, thromboembolism and/or thrombophilia.
• Currently on 2 or more tablets of any oral contraceptive pills per day at study entry
• Having 2 or more DMPA injections in the past 12 months or having DMPA injection in the past 90 days
• Leuprolide acetate injection in the past 30 days
• Smoker over the age of 35
• Women with estrogen dependent tumor e.g. breast cancer.
• Pregnancy.
• Underlying sickle cell anemia
• Women who are taking chemotherapeutic agents known to cause ovarian failure such as alkylating agents
• Allergy to any medication in this protocol

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Overall Clinical Trial Officials and Contacts

Overall Contact: Patient Recruitment and Public Liaison Office (800) 411-1222 prpl@mail.cc.nih.gov

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00556400

Study ID Number: 080022

ClinicalTrials.gov Identifier: NCT00556400

Health Authority: United States: Federal Government

NIH Clinical Center Detailed Web Page