Clomiphene Citrate in Infertile PCOS Patients

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Stefano Palomba, University Magna Graecia
ClinicalTrials.gov Identifier:
NCT00501839
First received: July 12, 2007
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

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 Intervention Phase
Polycystic Ovary Syndrome
Infertility
Drug: clomiphene citrate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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.

Resource links provided by NLM:


Further study details as provided by University Magna Graecia:

Primary Outcome Measures:
  • Cumulative pregnancy rate [ Time Frame: 12 months ]

Secondary Outcome Measures:
  • Ovulation rate Abortion rate Live-birth rate Adverse events Multiple pregnancy rate [ Time Frame: 21 months ]

Enrollment: 0
Study Start Date: August 2008
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00501839

Locations
Italy
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
  More Information

Publications:
Responsible Party: Stefano Palomba, Associate Professor, University Magna Graecia
ClinicalTrials.gov Identifier: NCT00501839     History of Changes
Other Study ID Numbers: 05/2006a
Study First Received: July 12, 2007
Last Updated: April 5, 2013
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by University Magna Graecia:
Anovulation
Clomiphene citrate
Infertility
PCOS
Treatment

Additional relevant MeSH terms:
Infertility
Polycystic Ovary Syndrome
Genital Diseases, Male
Genital Diseases, Female
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Citric Acid
Clomiphene
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on July 28, 2014