Aplastic AnemiaPhase 1/2NCT00556400
Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones
A Phase 1/2 study testing Lo-Ovral Oral Contraceptive Pills in people with Aplastic Anemia and Menorrhagia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 12 to 55 years, women only
- Conditions the study is for
- Aplastic Anemia, Menorrhagia, Amenorrhea
- What is being tested?
- Lo-Ovral Oral Contraceptive Pills
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Jun 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 55 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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 bone marrow failure, and other disease that require treatment with chemotherapy or stem cell transplantation 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.
Who cannot join
- Age less than 12 years
- Postmenopausal women
- Hormone level in menopausal range: Follicle Stimulating Hormone 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
Show all 14Show fewer
- Having 2 or more depo medroxyprogesterone acetate injections in the past 12 months or having depo medroxyprogesterone acetate 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Treatment of Menorrhagia in Women With Thrombocytopenia: Comparison of 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/microliter) 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/microliter. 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.
Read the detailed description
Low platelet counts can occur as a result of blood diseases like bone marrow failure, or from undergoing procedures such as chemotherapy treatment or stem cell transplantation. 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 thrombocytopenia secondary to bone marrow failure, chemotherapy and/or stem cell transplantation, 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 hemodynamically stable, menstruating women aged 12-55, who have bone marrow failure, or are undergoing chemotherapy and/or stem cell transplantation for other diseases with platelet levels less than 50,000/ microliter and present with heavy menstrual bleeding which is expected to last at least 2 weeks. 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 per microliter 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.
- Conditions
- Aplastic Anemia, Menorrhagia, Amenorrhea
- Being tested
- Lo-Ovral Oral Contraceptive Pills, Placebo - sugar pill
- Keywords
- Uterine Bleeding, Thrombocytopenia, Aplastic Anemia, Oral Contraceptive Pills, Menorrhagia
- Medical subject headings
- Anemia, Aplastic, Menorrhagia, Amenorrhea, Uterine Hemorrhage, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lo-Ovral Oral Contraceptive PillsDrug
Placebo - sugar pillDrug
| Study group | Role | What they receive |
|---|---|---|
| Lo-ovral | Active comparator | 1 tablet of lo-ovral is administered twice a day Receives: Drug: Lo-Ovral Oral Contraceptive Pills |
| sugar pill | Placebo comparator | Sugar pill was provided as a placebo Receives: Drug: Placebo - sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stop Vaginal Bleeding or Spotting.
Measured: 1 week
Secondary outcomes (2)
Proportion Who Stop Uterine Bleeding by Day 14.
Measured: 2 weeks
Total Number of Bleeding Days During the First 7 Days.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionJun 2012
- Study completionJun 2012
Why it stopped: Early termination because of insufficient accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Pamela Stratton, MD, Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00556400
- Sponsor's protocol ID
- 080022
- Other IDs
- 08-CH-0022
- Status last verified
- Jul 2013
- First submitted
- 9 Nov 2007
- Last updated
- 19 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Amsterdam A, Jakubowski A, Castro-Malaspina H, Baxi E, Kauff N, Krychman M, Stier E, Castiel M. Treatment of menorrhagia in women undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2004 Aug;34(4):363-6. doi: 10.1038/sj.bmt.1704577.
PubMed 15195079Girling JE, Rogers PA. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005;8(2):89-99. doi: 10.1007/s10456-005-9006-9. Epub 2005 Oct 7.
PubMed 16211359Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding? Hum Reprod. 2007 Mar;22(3):635-43. doi: 10.1093/humrep/del478. Epub 2007 Jan 4.
PubMed 17204526
Study at a glance
From the registry record, last updated by the sponsor on 19 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Menorrhagia in Women With Thrombocytopenia: Comparison of Platelet Transfusion Alone to Platelet Transfusion With Continuous Oral Contraceptive Pills
- ClinicalTrials.gov ID
- NCT00556400
- Acronym / sponsor ID
- 080022
- Conditions
- Aplastic Anemia, Menorrhagia, Amenorrhea
- Keywords
- Uterine Bleeding, Thrombocytopenia, Aplastic Anemia, Oral Contraceptive Pills, Menorrhagia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination because of insufficient accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Nov 2007
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 12 Nov 2007 (estimated)
- Results
- Posted 11 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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/microliter) 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/microliter. 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.
Detailed description
Low platelet counts can occur as a result of blood diseases like bone marrow failure, or from undergoing procedures such as chemotherapy treatment or stem cell transplantation. 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 thrombocytopenia secondary to bone marrow failure, chemotherapy and/or stem cell transplantation, 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 hemodynamically stable, menstruating women aged 12-55, who have bone marrow failure, or are undergoing chemotherapy and/or stem cell transplantation for other diseases with platelet levels less than 50,000/ microliter and present with heavy menstrual bleeding which is expected to last at least 2 weeks. 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 per microliter 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lo-ovral | Active comparator | Drug: Lo-Ovral Oral Contraceptive Pills1 tablet of lo-ovral is administered twice a day |
| sugar pill | Placebo comparator | Drug: Placebo - sugar pillSugar pill was provided as a placebo |
Who may qualify
- Ages
- 12 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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 bone marrow failure, and other disease that require treatment with chemotherapy or stem cell transplantation 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.
Key exclusion criteria (14 listed)
- Age less than 12 years
- Postmenopausal women
- Hormone level in menopausal range: Follicle Stimulating Hormone 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lo-Ovral Oral Contraceptive Pills | Drug | Lo-ovral |
| Placebo - sugar pill | Drug | sugar pill |
Primary outcome
Stop Vaginal Bleeding or Spotting.
Time frame: 1 week
2 secondary outcomes
Proportion Who Stop Uterine Bleeding by Day 14.
Time frame: 2 weeks
Total Number of Bleeding Days During the First 7 Days.
Time frame: 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15195079Amsterdam A, Jakubowski A, Castro-Malaspina H, Baxi E, Kauff N, Krychman M, Stier E, Castiel M. Treatment of menorrhagia in women undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 2004 Aug;34(4):363-6. doi: 10.1038/sj.bmt.1704577.
- Background: PubMed 16211359Girling JE, Rogers PA. Recent advances in endometrial angiogenesis research. Angiogenesis. 2005;8(2):89-99. doi: 10.1007/s10456-005-9006-9. Epub 2005 Oct 7.
- Background: PubMed 17204526Fraser IS, Critchley HO, Munro MG, Broder M. Can we achieve international agreement on terminologies and definitions used to describe abnormalities of menstrual bleeding? Hum Reprod. 2007 Mar;22(3):635-43. doi: 10.1093/humrep/del478. Epub 2007 Jan 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela Stratton, MD principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lo-Ovral Oral Contraceptive Pills in people with Aplastic Anemia and Menorrhagia, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stop Vaginal Bleeding or Spotting. (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00556400, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2013.