ContraceptionNCT00789802
A Randomized Controlled Trial of Oral Naproxen and Transdermal Estradiol for Bleeding in LNG-IUC
A study testing transdermal estradiol and naproxen in people with Contraception and Bleeding, run by Washington University School of Medicine at 1 site in United States.
Trial summary
We hypothesize that the addition of oral naproxen or transdermal estradiol will decrease the number of days of unscheduled bleeding experienced by first-time users of the levonorgestrel intrauterine system (LNG-IUC) during the first 12 weeks of use compared to an oral placebo. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Contraception, Bleeding
- What is being tested?
- transdermal estradiol and naproxen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Jan 2011
- Phase
- Interventional
- 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 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Must be of reproductive age from 18 to 45 years
- Must be choosing LNG-IUC for contraception
- Must be English-speaking
- Be willing to avoid additional use of exogenous hormones, such as oral contraceptives, for the duration of the study
- Be willing to avoid additional use of nonsteroidal antiinflammatory drugs, such as ibuprofen or aspirin for the duration of the study
- Be willing to comply with the study protocol, keep the bleeding diary and comply with follow-up visits and telephone interviews as scheduled
- Be willing and able to provide informed consent
Who cannot join
- Known or suspected pregnancy
- Contraindication to estrogen use, such as presence or history of:
- venous thromboembolism
- Arterial thrombosis
- Thrombophilia disorders, or known family history of
- Hypertension
Show all 27Show fewer
- Migraine headaches with aura or focal neurologic involvement, or any migraine over age 35 years
- Recent or planned future major surgery which will result in prolonged immobilization during the study period
- Presence or history of severe hepatic disease or liver tumors
- Known or suspected estrogen-dependent neoplasm
- Vaginal bleeding of unknown etiology
- Any cigarette smoking and age over 35 years
- Contraindications to nonsteroidal anti-inflammatory use, such as presence or history of:
- Gastrointestinal ulcer disease
- Renal insufficiency or failure
- Aspirin-induced asthma or hypersensitivity reaction
- Systemic lupus erythematosus (SLE) and mixed connective tissue disorders
- Use of anticoagulants
- Cardiovascular disease
- Use of medications that alter estrogen metabolism, i.e. rifampin, certain anti-seizure medications
- Regular use of an NSAID
- Current diagnosis of menorrhagia, metrorrhagia, symptomatic uterine fibroids, or endometrial polyp
- Hypersensitivity or allergy to any of the components of the estradiol patch
- Use of injectable contraception within 6 months of the start of the study medication
- Delivery or abortion in the previous 4 weeks
- Prior use of LNG-IUD
- Any condition, that in the opinion of the investigator, would contraindicate study participation
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School fo Medicine
St Louis, Missouri, 63110
About this study
Official title: A Randomized, Controlled Trial of Oral Naproxen and Transdermal Estradiol for Prevention of Unscheduled Bleeding in New Users of Levonorgestrel Intrauterine Contraception
We hypothesize that the addition of oral naproxen or transdermal estradiol will decrease the number of days of unscheduled bleeding experienced by first-time users of the levonorgestrel intrauterine system (LNG-IUC) during the first 12 weeks of use compared to an oral placebo. The objective of this study is to compare the total number of days of bleeding experienced by first time users of the LNG-IUC randomized to oral naproxen or estradiol patch compared to those randomized to placebo for the first 12 weeks of use. We will enroll women initiating LNG-IUC to one of 3 groups, transdermal estrogen, oral naproxen or oral placebo. We will enroll a total of 114 women, 38 in each group. Women will keep bleeding diaries for 16 weeks which will be used to calculate the total number of bleeding or spotting days. Statistical analysis will be performed to evaluate if there is less bleeding among the treatment arms then the placebo arm.
Read the detailed description
The levonorgestrel intrauterine system (LNG-IUC) is one of the most effective, reversible methods of contraception currently available in the United States. User satisfaction is overall high , however the most often cited reason for discontinuation is irregular bleeding . The LNG-IUC has mainly progesteronic effects on the uterine cavity. Morphological changes of the endometrium are observed, including stromal pseudo-decidualization and glandular atrophy . These endometrial changes may contribute to the irregular uterine bleeding experienced by women using the LNG-IUC. Up to 14% of women will discontinue the LNG-IUC within the 5-year period due to abnormal bleeding and up to 66% of woman who request removal of the LNG-IUC will do so in the first 6 months of use . Women may be less likely to discontinue the LNG-IUC due to abnormal bleeding patterns if they are counseled appropriately beforehand, however the prospect of irregular bleeding with few options for management may dissuade some women from even trying the LNG-IUC. A recent Cochrane review identified the need for further investigation into the treatment of irregular uterine bleeding caused by progestin only contraception .
One treatment for progestin-induced irregular bleeding is the administration of nonsteroidal anti-inflammatory agents (NSAIDs). A 1999 study showed a significant decrease in the number of bleeding days in women using the levonorgestrel sub-dermal implant randomized to mefenamic acid 500 mg compared to placebo . A 2004 study found a 50% reduction in bleeding in depot medroxyprogesterone (DPMA) users randomized to mefenamic acid versus placebo . There have been no studies looking specifically at NSAIDs for the prevention or treatment of LNG-IUC related irregular bleeding. Naproxen is an antiprostaglandin that is commonly used in gynecological practice for relief of dysmenorrhea and has been used to treat menorrhagia. It is widely available, inexpensive, well-tolerated and has a low incidence of side effects.
Previous studies have also shown the administration of estrogen alone and estrogen-containing oral contraceptives to users of subdermal levonorgestrel implants (Norplant®) resulted in decreased frequency of irregular uterine bleeding , . A prior randomized, controlled trial found a 0.1mg estradiol patch resulted in the clinical improvement of abnormal bleeding, however this finding was not statistically significant . A randomized, controlled trial of DMPA users found the cyclic administration of 0.1mg estradiol patches did not decreases irregular menstrual bleeding . In this study, the cyclic use of estrogen may have resulted in lower or inconsistent serum estradiol levels. Additionally, the progestational mechanism of action is more similar between levonorgestrel subdermal implants and LNG-IUC than depot medroxyprogesterone. No study has specifically addressed estrogen for treatment of irregular bleeding with the LNG-IUC.
- Conditions
- Contraception, Bleeding
- Being tested
- transdermal estradiol, naproxen, oral placebo
- Keywords
- contraception, progestin contraception, intrauterine contraception, unscheduled bleeding, placebo
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transdermal estradiolDrug
Also called Climara
transdermal estradiol 0.1mg patch to be changed weekly for 12 weeks.
naproxenDrug
Also called Naprosyn, Anaprox
naproxen 500mg by mouth twice daily for the first 5 days of every 4 week period for a total of 12 weeks
oral placeboDrug
oral placebo to be taken by mouth twice daily for the first 5 days of a 4 week block for a total of 5 weeks
| Study group | Role | What they receive |
|---|---|---|
| transdermal estradiol | Experimental | participants will be randomized to transdermal estradiol Receives: Drug: transdermal estradiol |
| oral naproxen | Experimental | participants will be randomized to oral naproxen Receives: Drug: naproxen |
| oral placebo | Placebo comparator | participants will be randomized to oral placebo Receives: Drug: oral placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Bleeding and Spotting Days
The median number of bleeding and spotting days reported at 12 weeks.
Measured: 12 weeks
Secondary outcomes (3)
Number of Bleeding Days Observed in Women With a LNG-IUC Treated With Naproxen, Estradiol and Placebo.
Median number of bleeding days observed in women with a LNG-IUC treated with naproxen, estradiol and placebo at 16 weeks.
Measured: 16 weeks
Patient Satisfaction With the LNG-IUC at the End of the 12 Weeks Between the 3 Study Groups.
To compare the level of patient satisfaction with the LNG-IUC at the end of the 12 weeks between the 3 study groups.
Measured: 12 weeks
Continuation Rates of the LNG-IUC at the End of the 12 Week Between the 3 Study Groups
To compare continuation rates of the LNG-IUC at the end of the 12 week between the 3 study groups
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2008 (estimated)
- Study startNov 2008
- Primary completionJan 2010
- Study completionJan 2011
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.
- Other trials for ContraceptionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists
- Responsible party
- Principal investigator, Tessa Madden, MD, Washington University School of Medicine
- Investigators
- Tessa E Madden, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00789802
- Sponsor's protocol ID
- 07-1026
- Status last verified
- Mar 2018
- First submitted
- 11 Nov 2008
- Last updated
- 20 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Controlled Trial of Oral Naproxen and Transdermal Estradiol for Prevention of Unscheduled Bleeding in New Users of Levonorgestrel Intrauterine Contraception
- ClinicalTrials.gov ID
- NCT00789802
- Acronym / sponsor ID
- 07-1026
- Conditions
- Contraception, Bleeding
- Keywords
- contraception, progestin contraception, intrauterine contraception, unscheduled bleeding, placebo
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- American College of Obstetricians and Gynecologists
- Study start
- Nov 2008
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 13 Nov 2008 (estimated)
- Results
- Posted 11 Dec 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
We hypothesize that the addition of oral naproxen or transdermal estradiol will decrease the number of days of unscheduled bleeding experienced by first-time users of the levonorgestrel intrauterine system (LNG-IUC) during the first 12 weeks of use compared to an oral placebo. The objective of this study is to compare the total number of days of bleeding experienced by first time users of the LNG-IUC randomized to oral naproxen or estradiol patch compared to those randomized to placebo for the first 12 weeks of use. We will enroll women initiating LNG-IUC to one of 3 groups, transdermal estrogen, oral naproxen or oral placebo. We will enroll a total of 114 women, 38 in each group. Women will keep bleeding diaries for 16 weeks which will be used to calculate the total number of bleeding or spotting days. Statistical analysis will be performed to evaluate if there is less bleeding among the treatment arms then the placebo arm.
Detailed description
The levonorgestrel intrauterine system (LNG-IUC) is one of the most effective, reversible methods of contraception currently available in the United States. User satisfaction is overall high , however the most often cited reason for discontinuation is irregular bleeding . The LNG-IUC has mainly progesteronic effects on the uterine cavity. Morphological changes of the endometrium are observed, including stromal pseudo-decidualization and glandular atrophy . These endometrial changes may contribute to the irregular uterine bleeding experienced by women using the LNG-IUC. Up to 14% of women will discontinue the LNG-IUC within the 5-year period due to abnormal bleeding and up to 66% of woman who request removal of the LNG-IUC will do so in the first 6 months of use . Women may be less likely to discontinue the LNG-IUC due to abnormal bleeding patterns if they are counseled appropriately beforehand, however the prospect of irregular bleeding with few options for management may dissuade some women from even trying the LNG-IUC. A recent Cochrane review identified the need for further investigation into the treatment of irregular uterine bleeding caused by progestin only contraception .
One treatment for progestin-induced irregular bleeding is the administration of nonsteroidal anti-inflammatory agents (NSAIDs). A 1999 study showed a significant decrease in the number of bleeding days in women using the levonorgestrel sub-dermal implant randomized to mefenamic acid 500 mg compared to placebo . A 2004 study found a 50% reduction in bleeding in depot medroxyprogesterone (DPMA) users randomized to mefenamic acid versus placebo . There have been no studies looking specifically at NSAIDs for the prevention or treatment of LNG-IUC related irregular bleeding. Naproxen is an antiprostaglandin that is commonly used in gynecological practice for relief of dysmenorrhea and has been used to treat menorrhagia. It is widely available, inexpensive, well-tolerated and has a low incidence of side effects.
Previous studies have also shown the administration of estrogen alone and estrogen-containing oral contraceptives to users of subdermal levonorgestrel implants (Norplant®) resulted in decreased frequency of irregular uterine bleeding , . A prior randomized, controlled trial found a 0.1mg estradiol patch resulted in the clinical improvement of abnormal bleeding, however this finding was not statistically significant . A randomized, controlled trial of DMPA users found the cyclic administration of 0.1mg estradiol patches did not decreases irregular menstrual bleeding . In this study, the cyclic use of estrogen may have resulted in lower or inconsistent serum estradiol levels. Additionally, the progestational mechanism of action is more similar between levonorgestrel subdermal implants and LNG-IUC than depot medroxyprogesterone. No study has specifically addressed estrogen for treatment of irregular bleeding with the LNG-IUC.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| transdermal estradiol | Experimental | Drug: transdermal estradiolparticipants will be randomized to transdermal estradiol |
| oral naproxen | Experimental | Drug: naproxenparticipants will be randomized to oral naproxen |
| oral placebo | Placebo comparator | Drug: oral placeboparticipants will be randomized to oral placebo |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Must be of reproductive age from 18 to 45 years
- Must be choosing LNG-IUC for contraception
- Must be English-speaking
- Be willing to avoid additional use of exogenous hormones, such as oral contraceptives, for the duration of the study
- Be willing to avoid additional use of nonsteroidal antiinflammatory drugs, such as ibuprofen or aspirin for the duration of the study
Key exclusion criteria (27 listed)
- Known or suspected pregnancy
- Contraindication to estrogen use, such as presence or history of:
- Recent or planned future major surgery which will result in prolonged immobilization during the study period
- Presence or history of severe hepatic disease or liver tumors
- Known or suspected estrogen-dependent neoplasm
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 |
|---|---|---|
| transdermal estradiolAlso: Climaratransdermal estradiol 0.1mg patch to be changed weekly for 12 weeks. | Drug | transdermal estradiol |
| naproxenAlso: Naprosyn, Anaproxnaproxen 500mg by mouth twice daily for the first 5 days of every 4 week period for a total of 12 weeks | Drug | oral naproxen |
| oral placebooral placebo to be taken by mouth twice daily for the first 5 days of a 4 week block for a total of 5 weeks | Drug | oral placebo |
Primary outcome
Number of Bleeding and Spotting Days
Time frame: 12 weeks
The median number of bleeding and spotting days reported at 12 weeks.
3 secondary outcomes
Number of Bleeding Days Observed in Women With a LNG-IUC Treated With Naproxen, Estradiol and Placebo.
Time frame: 16 weeks
Patient Satisfaction With the LNG-IUC at the End of the 12 Weeks Between the 3 Study Groups.
Time frame: 12 weeks
Continuation Rates of the LNG-IUC at the End of the 12 Week Between the 3 Study Groups
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Tessa E Madden, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing transdermal estradiol and naproxen in people with Contraception and Bleeding, run by Washington University School of Medicine 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 7 inclusion and 27 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: finished, as of the sponsor's last update on 20 Mar 2018. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2014). 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?
Number of Bleeding and Spotting Days (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2018.