Polycystic Ovary SyndromePhase 4NCT00501839
Clomiphene Citrate in Infertile PCOS Patients
A Phase 4 study testing clomiphene citrate in people with Polycystic Ovary Syndrome and Infertility, run by University Magna Graecia at 1 site in Italy.
Trial summary
Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Clomiphene citrate (CC) represents the first therapeutic option for treating the anovulatory infertility in PCOS patients because it is characterized by low costs, limited dose-dependent side effects, and simplicity of administration… Read more about this study
- Who is it for?
- Ages 18 to 35 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Infertility
- What is being tested?
- clomiphene citrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteItaly
- Study dates
- Aug 2008to Sep 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 35 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Polycystic ovary syndrome (using NIH criteria)
- Anovulatory infertility (using WHO criteria)
- Previous three CC-stimulated ovulatory cycles
Who cannot join
- Age <18 or >35 years
- Severe obesity (BMI >35)
- Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses
- Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia
- Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugs
- Intention to start a diet or a specific program of physical activity
Show all 10Show fewer
- Organic pelvic diseases
- Previous pelvic surgery
- Suspected peritoneal factor infertility
- Tubal or male factor infertility or sub-fertility
Trial locations and contacts
1 site in 1 country.
About this study
Official title: How Long Should First-line Treatment be Continued in Infertile PCOS Patients Who Ovulate Under Clomiphene Citrate? A Randomized Controlled Clinical Study.
Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Clomiphene citrate (CC) represents the first therapeutic option for treating the anovulatory infertility in PCOS patients because it is characterized by low costs, limited dose-dependent side effects, and simplicity of administration and management due to no need for ongoing monitoring.
Excellent results in terms of ovulations have been obtained using CC. However, only 50% of patients who ovulates under CC will conceive. The exact explanation for the discrepancy between the ovulation and pregnancy rates is unknown, but several hypotheses on the anti-estrogenic effects that CC exerts on the ovary and uterus have been suggested.
To date, few data are available on the optimal schedule for CC administration, and it is unknown how long patients who ovulate under CC should continue treatment before switching to second-line ovulation induction therapy. The aim of the study was to define the clinical benefits of CC administration according to its duration of administration.
Read the detailed description
Infertile PCOS patients who had three previous ovulatory cycles under CC will be enrolled and randomized in three groups (groups A, B, and C). In group A, patients will receive cyclic progestogens for nine months; in group B, patients will continue CC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens; and in group C, patients will continue CC administration at the same ovulating doses for nine cycles. In each case, CC will be administered using a traditional incremental-doses protocol up to 150 mg daily.
All patients eligible will undergo baseline assessment consisting of anthropometric, hormonal, and ultrasonographic evaluations. During the study, the clinical and reproductive outcomes, and the adverse experience will be evaluated in each patient.
Data will be analyzed using the intention-to-treat principle and a P value of 0.05 or less will be considered significant. Continuous variables will be analyzed with the unpaired t test and general linear model for repeated measures analysis with Bonferroni test for the post-hoc analysis as required. For categorical variables, the Pearson chi-square and Fisher's exact tests will be used. Cumulative pregnancy rate, our primary end-point, will be calculated by the Kaplan-Maier method, and the differences between the two groups will be assessed with the log-rank test. Cox proportional-hazards model will be used to calculate the hazard ratio for new pregnancy in both groups.
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Being tested
- clomiphene citrate
- Keywords
- Anovulation, Clomiphene citrate, Infertility, PCOS, Treatment
- Medical subject headings
- Polycystic Ovary Syndrome, Infertility, Anovulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clomiphene citrateDrug
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Cyclic progestogens for nine months Receives: Drug: clomiphene citrate |
| Group B | Active comparator | CC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens Receives: Drug: clomiphene citrate |
| Group C | Active comparator | CC administration at the same ovulating doses for nine cycles Receives: Drug: clomiphene citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative pregnancy rate
Measured: 12 months
Secondary outcomes (1)
Ovulation rate Abortion rate Live-birth rate Adverse events Multiple pregnancy rate
Measured: 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2007 (estimated)
- Study startAug 2008
- Primary completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefano Palomba, University Magna Graecia
- Investigators
- Stefano Palomba, MD, Principal investigator, Department of Obstetrics & Gynecology, University "Magna Graecia" of CatanzaroFrancesco Orio, MD, Principal investigator, Department of Endocrinology, University "Federico II" of NaplesAchille Tolino, MD, Principal investigator, Department of Obstetrics & Gynecology, University "Federico II" of Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00501839
- Sponsor's protocol ID
- 05/2006a
- Status last verified
- Apr 2013
- First submitted
- 12 Jul 2007
- Last updated
- 9 Apr 2013
- Results posted
- No
Publications
Palomba S, Orio F Jr, Falbo A, Russo T, Tolino A, Zullo F. Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Sep;92(9):3498-503. doi: 10.1210/jc.2007-1009. Epub 2007 Jun 26.
PubMed 17595241Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.
PubMed 15840746
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- How Long Should First-line Treatment be Continued in Infertile PCOS Patients Who Ovulate Under Clomiphene Citrate? A Randomized Controlled Clinical Study.
- ClinicalTrials.gov ID
- NCT00501839
- Acronym / sponsor ID
- 05/2006a
- Conditions
- Polycystic Ovary Syndrome, Infertility
- Keywords
- Anovulation, Clomiphene citrate, Infertility, PCOS, Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Sep 2010 (actual)
- First posted
- 16 Jul 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Clomiphene citrate (CC) represents the first therapeutic option for treating the anovulatory infertility in PCOS patients because it is characterized by low costs, limited dose-dependent side effects, and simplicity of administration and management due to no need for ongoing monitoring.
Excellent results in terms of ovulations have been obtained using CC. However, only 50% of patients who ovulates under CC will conceive. The exact explanation for the discrepancy between the ovulation and pregnancy rates is unknown, but several hypotheses on the anti-estrogenic effects that CC exerts on the ovary and uterus have been suggested.
To date, few data are available on the optimal schedule for CC administration, and it is unknown how long patients who ovulate under CC should continue treatment before switching to second-line ovulation induction therapy. The aim of the study was to define the clinical benefits of CC administration according to its duration of administration.
Detailed description
Infertile PCOS patients who had three previous ovulatory cycles under CC will be enrolled and randomized in three groups (groups A, B, and C). In group A, patients will receive cyclic progestogens for nine months; in group B, patients will continue CC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens; and in group C, patients will continue CC administration at the same ovulating doses for nine cycles. In each case, CC will be administered using a traditional incremental-doses protocol up to 150 mg daily.
All patients eligible will undergo baseline assessment consisting of anthropometric, hormonal, and ultrasonographic evaluations. During the study, the clinical and reproductive outcomes, and the adverse experience will be evaluated in each patient.
Data will be analyzed using the intention-to-treat principle and a P value of 0.05 or less will be considered significant. Continuous variables will be analyzed with the unpaired t test and general linear model for repeated measures analysis with Bonferroni test for the post-hoc analysis as required. For categorical variables, the Pearson chi-square and Fisher's exact tests will be used. Cumulative pregnancy rate, our primary end-point, will be calculated by the Kaplan-Maier method, and the differences between the two groups will be assessed with the log-rank test. Cox proportional-hazards model will be used to calculate the hazard ratio for new pregnancy in both groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: clomiphene citrateCyclic progestogens for nine months |
| Group B | Active comparator | Drug: clomiphene citrateCC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens |
| Group C | Active comparator | Drug: clomiphene citrateCC administration at the same ovulating doses for nine cycles |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Polycystic ovary syndrome (using NIH criteria)
- Anovulatory infertility (using WHO criteria)
- Previous three CC-stimulated ovulatory cycles
Key exclusion criteria (10 listed)
- Age <18 or >35 years
- Severe obesity (BMI >35)
- Neoplastic, metabolic, hepatic, and cardiovascular disorders or other concurrent medical illnesses
- Hypothyroidism, hyperprolactinemia, Cushing's syndrome, and non-classical congenital adrenal hyperplasia
- Current or previous (within the last six months) use of oral contraceptives, glucocorticoids, antiandrogens, antidiabetic and anti-obesity drugs or other hormonal drugs
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 |
|---|---|---|
| clomiphene citrate | Drug | Group A, Group B, Group C |
Primary outcome
Cumulative pregnancy rate
Time frame: 12 months
1 secondary outcome
Ovulation rate Abortion rate Live-birth rate Adverse events Multiple pregnancy rate
Time frame: 21 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2013.
- Background: PubMed 17595241Palomba S, Orio F Jr, Falbo A, Russo T, Tolino A, Zullo F. Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007 Sep;92(9):3498-503. doi: 10.1210/jc.2007-1009. Epub 2007 Jun 26.
- Background: PubMed 15840746Palomba S, Orio F Jr, Falbo A, Manguso F, Russo T, Cascella T, Tolino A, Carmina E, Colao A, Zullo F. Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Jul;90(7):4068-74. doi: 10.1210/jc.2005-0110. Epub 2005 Apr 19.
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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.
Stefano Palomba, MD principal investigator
Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro
Francesco Orio, MD principal investigator
Department of Endocrinology, University "Federico II" of Naples
Achille Tolino, MD principal investigator
Department of Obstetrics & Gynecology, University "Federico II" of Naples
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 citrate in people with Polycystic Ovary Syndrome and Infertility, run by University Magna Graecia at 1 site in Italy.
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 3 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: withdrawn, as of the sponsor's last update on 9 Apr 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 Italy. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Cumulative pregnancy rate (time frame: 12 months). 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 NCT00501839, which also lists 2 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 9 Apr 2013.