Clomiphene Citrate in Infertile PCOS Patients

Sponsor

University Magna Graecia (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00501839

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief 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 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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome Infertility	Drug: clomiphene citrate	Phase 4

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

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

How Long Should First-line Treatment be Continued in Infertile PCOS Patients Who Ovulate Under Clomiphene Citrate? A Randomized Controlled Clinical Study.

Study Start Date :

Aug 1, 2008

Actual Primary Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group A Cyclic progestogens for nine months	Drug: clomiphene citrate
Active Comparator: Group B CC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens	Drug: clomiphene citrate
Active Comparator: Group C CC administration at the same ovulating doses for nine cycles	Drug: clomiphene citrate

Arm

Intervention/Treatment

Active Comparator: Group A

Cyclic progestogens for nine months

Drug: clomiphene citrate

Active Comparator: Group B

CC treatment for further three cycles at the same ovulating doses followed by six months of cyclic progestogens

Drug: clomiphene citrate

Active Comparator: Group C

CC administration at the same ovulating doses for nine cycles

Drug: clomiphene citrate

Outcome Measures

Primary Outcome Measures

Cumulative pregnancy rate [12 months]

Secondary Outcome Measures

Ovulation rate Abortion rate Live-birth rate Adverse events Multiple pregnancy rate [21 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Polycystic ovary syndrome (using NIH criteria)
Anovulatory infertility (using WHO criteria)
Previous three CC-stimulated ovulatory cycles

Exclusion Criteria:

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
Organic pelvic diseases
Previous pelvic surgery
Suspected peritoneal factor infertility
Tubal or male factor infertility or sub-fertility

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pugliese Hospital	Catanzaro	Catanzaro, CZ, Italy	Italy	88100

Sponsors and Collaborators

University Magna Graecia

Investigators

Principal Investigator: Stefano Palomba, MD, Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro
Principal Investigator: Francesco Orio, MD, Department of Endocrinology, University "Federico II" of Naples
Principal Investigator: Achille Tolino, MD, Department of Obstetrics & Gynecology, University "Federico II" of Naples