Polycystic Ovary SyndromePhase 4NCT02802865
Combined Letrozole and Clomid in Women With Infertility and PCOS
A Phase 4 study testing Clomiphene and Letrozole in people with Polycystic Ovary Syndrome and Infertility, run by Rachel Mejia at 1 site in United States.
Trial summary
This study evaluates the addition of clomid to letrozole for the treatment of infertility in women with polycystic ovary syndrome. Half of the participants will receive letrozole and clomid in combination, while the other half will receive letrozole alone. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Infertility
- What is being tested?
- Clomiphene and Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Feb 2019
- Phase
- Phase 4
- 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 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Willing to comply with all study procedures and be available for the duration of the study
- Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular timed unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older
- Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria
- Ability to have regular intercourse during the ovulation induction phase of the study
- Normal sperm concentration of 15 million/mL and with normal motility of > 40% according to World Health Organization cutoff points, in at least one ejaculate during the previous year
Who cannot join
- Current pregnancy
- Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months
- Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
- Uncorrected thyroid disease
- Untreated hyperprolactinemia.
- Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension
Show all 10Show fewer
- Contraindications to clomiphene citrate: hypersensitivity to CC or any of its components, history of liver disease or known liver disease, unknown cause of abnormal uterine bleeding, or intracranial lesion
- Contraindications to letrozole: hypersensitivity to letrozole or any of its components.
- Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month.
- If patients are suspected based on clinical findings for other etiologies that mimic PCOS, work up must be completed to exclude other etiologies prior to enrollment (i.e. Cushing's syndrome, androgen-secreting tumor).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
About this study
Official title: Combined Letrozole and Clomid in Polycystic Ovary Syndrome: a Randomized Control Trial of Combination of Letrozole and Clomiphene Citrate or Letrozole Alone for the Treatment of Infertility in Women With Polycystic Ovary Syndrome
This study evaluates the addition of clomid to letrozole for the treatment of infertility in women with polycystic ovary syndrome. Half of the participants will receive letrozole and clomid in combination, while the other half will receive letrozole alone.
Read the detailed description
Letrozole and Clomid are both used for ovulation induction, but they have different mechanisms of action. Letrozole has been shown to be superior to clomid in achieving live birth rates in women with infertility and polycystic ovary syndrome. However, the combination of these medications has not been studied. This is a pilot study to evaluate if the combination treatment has improved efficacy as measured by ovulation rate.
This is a randomized controlled trial of letrozole versus letrozole and clomiphene citrate (CC) for one menstrual cycle. Women will be randomized in a 1:1 ratio to receive letrozole 2.5 mg or combination of letrozole 2.5 mg and clomiphene 50 mg for 5 days on days 3-7 of menstrual cycle. The women and their partners will be instructed to have regular intercourse with the intent to conceive during the cycle. Patients will have an transvaginal ultrasound mid cycle and to evaluate number of follicles (>15 mm), follicle size, endometrial thickness and pattern. Patients will have mid- luteal phase progesterone level drawn to evaluate ovulation. Side effect profile will also be monitored.
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Being tested
- Clomiphene, Letrozole
- Medical subject headings
- Polycystic Ovary Syndrome, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClomipheneDrug
Also called clomid, clomiphene citrate
LetrozoleDrug
Also called femara
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Active comparator | Letrozole 2.5 mg orally for 5 days on cycle days 3-7 Receives: Drug: Letrozole |
| Letrozole + Clomiphene | Experimental | Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 Receives: Drug: Clomiphene; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level
Ovulation: mid-luteal progesterone > /=3 ng/mL. No ovulation: mid-luteal progesterone <3ng/mL.
Measured: 7 days following LH surge or at cycle day 21 if no LH surge was detected
Secondary outcomes (8)
Number of Developing Follicles
Number of follicles measuring > 10mm on ultrasound
Measured: Cycle day 12-14
Size of Largest Developing Follicle
Size of largest follicle on ultrasound
Measured: Cycle day 12-14
Endometrial Thickness
Thickness of endometrial lining assessed by ultrasound
Measured: Cycle day 12-14
Conception
Conception: a positive serum or urinary test of hCG; No conception: Neither a positive serum or urinary test of hCG
Measured: 5 weeks after treatment
Clinical Pregnancy
Clinical Pregnancy: an intrauterine pregnancy with fetal heart motion determined by ultrasonography; No Clinical Pregnancy: no intrauterine pregnancy with fetal heart motion determined by ultrasonography
Measured: 6-7 weeks after treatment
Multiple Gestation
Multiple Gestation: an intrauterine pregnancy with multiple fetal heart rates determined by ultrasonography; No Multiple Gestation: either no intrauterine pregnancy, or an intrauterine pregnancy with a single fetal heart rate determined by ultrasonography
Measured: 9-10 months after treatment
Live Birth
Live Birth: delivery of a live infant; No Live Birth: no delivery of a live infant
Measured: 9-10 months after treatment
Pregnancy Loss
Pregnancy Loss: any pregnancy loss including biochemical pregnancy, ectopic pregnancy, and miscarriage; No Pregnancy Loss: no pregnancy loss including biochemical pregnancy, ectopic pregnancy, or miscarriage.
Measured: 9-10 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2016 (estimated)
- Study startAug 2016
- Primary completionMay 2018
- Study completionFeb 2019
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 (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rachel Mejia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Rachel Mejia, University of Iowa
- Investigators
- Rachel Mejia, DO, Principal investigator, University of Iowa Hosptials & ClinicsBrad Van Voorhis, MD, Principal investigator, University of Iowa Hospitals & Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02802865
- Sponsor's protocol ID
- 201606806
- Status last verified
- Sep 2019
- First submitted
- 9 Jun 2016
- Last updated
- 27 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2019 Mar;111(3):571-578.e1. doi: 10.1016/j.fertnstert.2018.11.030. Epub 2019 Jan 22.
PubMed 30683591
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Letrozole and Clomid in Polycystic Ovary Syndrome: a Randomized Control Trial of Combination of Letrozole and Clomiphene Citrate or Letrozole Alone for the Treatment of Infertility in Women With Polycystic Ovary Syndrome
- ClinicalTrials.gov ID
- NCT02802865
- Acronym / sponsor ID
- 201606806
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Rachel MejiaUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- May 2018 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 16 Jun 2016 (estimated)
- Results
- Posted 27 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the addition of clomid to letrozole for the treatment of infertility in women with polycystic ovary syndrome. Half of the participants will receive letrozole and clomid in combination, while the other half will receive letrozole alone.
Detailed description
Letrozole and Clomid are both used for ovulation induction, but they have different mechanisms of action. Letrozole has been shown to be superior to clomid in achieving live birth rates in women with infertility and polycystic ovary syndrome. However, the combination of these medications has not been studied. This is a pilot study to evaluate if the combination treatment has improved efficacy as measured by ovulation rate.
This is a randomized controlled trial of letrozole versus letrozole and clomiphene citrate (CC) for one menstrual cycle. Women will be randomized in a 1:1 ratio to receive letrozole 2.5 mg or combination of letrozole 2.5 mg and clomiphene 50 mg for 5 days on days 3-7 of menstrual cycle. The women and their partners will be instructed to have regular intercourse with the intent to conceive during the cycle. Patients will have an transvaginal ultrasound mid cycle and to evaluate number of follicles (>15 mm), follicle size, endometrial thickness and pattern. Patients will have mid- luteal phase progesterone level drawn to evaluate ovulation. Side effect profile will also be monitored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Active comparator | Drug: LetrozoleLetrozole 2.5 mg orally for 5 days on cycle days 3-7 |
| Letrozole + Clomiphene | Experimental | Drug: Clomiphene, Drug: LetrozoleLetrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomid 50 mg orally for 5 days on cycle days 3-7 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Willing to comply with all study procedures and be available for the duration of the study
- Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular timed unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older
- Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria
- Ability to have regular intercourse during the ovulation induction phase of the study
- Normal sperm concentration of 15 million/mL and with normal motility of > 40% according to World Health Organization cutoff points, in at least one ejaculate during the previous year
Key exclusion criteria (10 listed)
- Current pregnancy
- Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months
- Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
- Uncorrected thyroid disease
- Untreated hyperprolactinemia.
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 |
|---|---|---|
| ClomipheneAlso: clomid, clomiphene citrate | Drug | Letrozole + Clomiphene |
| LetrozoleAlso: femara | Drug | Letrozole, Letrozole + Clomiphene |
Primary outcome
Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level
Time frame: 7 days following LH surge or at cycle day 21 if no LH surge was detected
Ovulation: mid-luteal progesterone > /=3 ng/mL. No ovulation: mid-luteal progesterone <3ng/mL.
8 secondary outcomes
Number of Developing Follicles
Time frame: Cycle day 12-14
Size of Largest Developing Follicle
Time frame: Cycle day 12-14
Endometrial Thickness
Time frame: Cycle day 12-14
Conception
Time frame: 5 weeks after treatment
Clinical Pregnancy
Time frame: 6-7 weeks after treatment
Multiple Gestation
Time frame: 9-10 months after treatment
Live Birth
Time frame: 9-10 months after treatment
Pregnancy Loss
Time frame: 9-10 months after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30683591Mejia RB, Summers KM, Kresowik JD, Van Voorhis BJ. A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome. Fertil Steril. 2019 Mar;111(3):571-578.e1. doi: 10.1016/j.fertnstert.2018.11.030. Epub 2019 Jan 22.
- Individual participant dataSharing planned: No
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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.
Rachel Mejia, DO principal investigator
University of Iowa Hosptials & Clinics
Brad Van Voorhis, MD principal investigator
University of Iowa Hospitals & Clinics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Clomiphene and Letrozole in people with Polycystic Ovary Syndrome and Infertility, run by Rachel Mejia 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 5 inclusion and 10 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 27 Sep 2019. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 27 Sep 2019). 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 Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level (time frame: 7 days following LH surge or at cycle day 21 if no LH surge was detected). 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 NCT02802865, which also lists 1 linked publication.
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 27 Sep 2019; AzTrials last refreshed its copy on 8 Nov 2026.