Anovulatory Infertility Related to Polycystic Ovary SyndromePhase 4NCT00461643
Strategies for Ovulation Induction in Anovulatory Infertile Patients With PCOS
A Phase 4 study testing Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins in people with Anovulatory Infertility Related to Polycystic Ovary Syndrome, run by University Magna Graecia at 3 sites in Italy.
Trial summary
Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Even if several first-step treatments have been proposed for anovulatory infertile PCOS patients, very few data are available in literature regarding the best integrated strategy. Read more about this study
- Who is it for?
- Ages 18 to 35 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Anovulatory Infertility Related to Polycystic Ovary Syndrome
- What is being tested?
- Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 552 participants
- Where
- 3 sitesItaly
- Study dates
- Jan 2007to Dec 2015
- 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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Polycystic ovary syndrome (using ESHRE/ARSM 2004 criteria)
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
- Previous use of ovulation induction agents
Show all 12Show fewer
- Intention to start a diet or a specific program of physical activity
- No uterine bleeding after progesterone challenge test
- Organic pelvic diseases
- Previous pelvic surgery
- Suspected peritoneal factor infertility
- Tubal or male factor infertility or sub-fertility
Trial locations and contacts
3 sites in 1 country.
Italy3 sites, 3 recruiting
- Recruiting
"Pugliese" Hospital
Catanzaro, 88100
Ingrid Tomaino, MD, +39 0961 883234, angela.falbo@libero.it
Stefano Palomba, MD
- Recruiting
"Pugliese" Hospital
Catanzaro, 88100
Ingrid Tomaino, MD, +39 0961 883234, zullo@unicz.it
Stefano Palomba, MD
- Recruiting
Pugliese-Ciaccio Hospital
Catanzaro, 88100
MD
About this study
Official title: Comparison of Three Different Strategies for Treating Infertility in Anovulatory Women With Polycystic Ovary Syndrome: a Multicentre Randomized Controlled Clinical Trial
Anovulatory infertility is a common feature of the polycystic ovary syndrome (PCOS). Even if several first-step treatments have been proposed for anovulatory infertile PCOS patients, very few data are available in literature regarding the best integrated strategy. In fact, a single compound could be effective as first-step approach but not or less useful when integrated in a more complex strategy.
The goal of the current protocol will be to compare three different strategies for treating anovulatory infertility in PCOS patients having as primary end-point the multiple pregnancy rate.
Read the detailed description
All patients eligible will undergo baseline assessment consisting of antropometric, hormonal, and ultrasonographic assessments. Successively, patients enrolled will be allocated in three different strategies (strategy A, B, and C).
A total of 184 infertile PCOS patients per arm will be enrolled and treated with three different integrated strategies: clomiphene followed by clomiphene plus metformin followed by gonadotropins (strategy A); metformin followed by metformin plus clomiphene followed by gonadotropins(strategy B); and metformin plus clomiphene followed by gonadotropins(strategy C).
In all patients, the same regimen will be used to administered clomiphene, metformin, and gonadotropins.Both clomiphene and metformin will be administered at incremental doses in each case.Gonadotropins will be administrated to obtain a controlled ovarian stimulation using highly purified urinary FSH in a low-dose step-up protocol.
During the study, the clinical and reproductive outcomes, and adverse experiences will be evaluated in each woman.
- Being tested
- Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins
- Keywords
- Anovulation, Clomiphene citrate, Infertility, Metformin, PCOS, RCT, Treatment
- Medical subject headings
- Anovulation, Infertility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropinsDrug
| Study group | Role | What they receive |
|---|---|---|
| Strategy A | Active comparator | clomiphene followed by clomiphene plus metformin followed by gonadotropins Receives: Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins |
| Strategy B | Active comparator | metformin followed by metformin plus clomiphene followed by gonadotropins Receives: Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins |
| Strategy C | Active comparator | metformin plus clomiphene followed by gonadotropins Receives: Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropins |
What is being measured
The primary outcome is the main question the study is designed to answer.
Multiple pregnancy rate
Measured: 9 months
Secondary outcomes (5)
Ovulation rate
Measured: 15 months
Pregnancy rate
Measured: 15 months
Abortion rate
Measured: 15 months
Live-birth rate
Measured: 24 months
Adverse-events
Measured: 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2007 (estimated)
- Study startJan 2007
- Primary completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anovulatory Infertility Related to 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 552 participants (estimated)
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 and Gynecology, University "Magna Graecia" of Catanzaro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00461643
- Sponsor's protocol ID
- 01/2007
- Status last verified
- Apr 2013
- First submitted
- 13 Apr 2007
- Last updated
- 9 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Palomba 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 15840746Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006 Jun 24;332(7556):1485. doi: 10.1136/bmj.38867.631551.55. Epub 2006 Jun 12.
PubMed 16769748Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66. doi: 10.1056/NEJMoa063971.
PubMed 17287476
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
- Comparison of Three Different Strategies for Treating Infertility in Anovulatory Women With Polycystic Ovary Syndrome: a Multicentre Randomized Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT00461643
- Acronym / sponsor ID
- 01/2007
- Keywords
- Anovulation, Clomiphene citrate, Infertility, Metformin, PCOS, RCT, Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 552 participants (estimated)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Dec 2015 (estimated)
- First posted
- 18 Apr 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). Even if several first-step treatments have been proposed for anovulatory infertile PCOS patients, very few data are available in literature regarding the best integrated strategy. In fact, a single compound could be effective as first-step approach but not or less useful when integrated in a more complex strategy.
The goal of the current protocol will be to compare three different strategies for treating anovulatory infertility in PCOS patients having as primary end-point the multiple pregnancy rate.
Detailed description
All patients eligible will undergo baseline assessment consisting of antropometric, hormonal, and ultrasonographic assessments. Successively, patients enrolled will be allocated in three different strategies (strategy A, B, and C).
A total of 184 infertile PCOS patients per arm will be enrolled and treated with three different integrated strategies: clomiphene followed by clomiphene plus metformin followed by gonadotropins (strategy A); metformin followed by metformin plus clomiphene followed by gonadotropins(strategy B); and metformin plus clomiphene followed by gonadotropins(strategy C).
In all patients, the same regimen will be used to administered clomiphene, metformin, and gonadotropins.Both clomiphene and metformin will be administered at incremental doses in each case.Gonadotropins will be administrated to obtain a controlled ovarian stimulation using highly purified urinary FSH in a low-dose step-up protocol.
During the study, the clinical and reproductive outcomes, and adverse experiences will be evaluated in each woman.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Strategy A | Active comparator | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropinsclomiphene followed by clomiphene plus metformin followed by gonadotropins |
| Strategy B | Active comparator | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropinsmetformin followed by metformin plus clomiphene followed by gonadotropins |
| Strategy C | Active comparator | Drug: Clomiphene citrate, metformin, metformin plus clomiphene citrate, gonadotropinsmetformin plus clomiphene followed by gonadotropins |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Polycystic ovary syndrome (using ESHRE/ARSM 2004 criteria)
Key exclusion criteria (12 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, metformin, metformin plus clomiphene citrate, gonadotropins | Drug | Strategy A, Strategy B, Strategy C |
Primary outcome
Multiple pregnancy rate
Time frame: 9 months
5 secondary outcomes
Ovulation rate
Time frame: 15 months
Pregnancy rate
Time frame: 15 months
Abortion rate
Time frame: 15 months
Live-birth rate
Time frame: 24 months
Adverse-events
Time frame: 15
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2013.
- 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.
- Background: PubMed 16769748Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006 Jun 24;332(7556):1485. doi: 10.1136/bmj.38867.631551.55. Epub 2006 Jun 12.
- Background: PubMed 17287476Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, Steinkampf MP, Coutifaris C, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Giudice LC, Leppert PC, Myers ER; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007 Feb 8;356(6):551-66. doi: 10.1056/NEJMoa063971.
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 and Gynecology, University "Magna Graecia" of Catanzaro
3 sites 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, metformin, metformin plus clomiphene citrate, gonadotropins in people with Anovulatory Infertility Related to Polycystic Ovary Syndrome, run by University Magna Graecia at 3 sites 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 1 inclusion and 12 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: status not confirmed, 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 3 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Stefano Palomba, MD (+39-0961.883234, stefanopalomba@tin.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Multiple pregnancy rate (time frame: 9 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 NCT00461643, 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 9 Apr 2013.