Clinical trial NCT00501787: Metformin Administration in Infertile Anovulatory PCOS Patients
Official title: Tailored Versus Non-tailored Metformin Protocol for Ovulation Induction in Infertile Anovulatory PCOS Patients. A Randomized Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Keywords: Anovulation
metformin
PCOS
treatment
Lead sponsor: University Magna Graecia
Sponsor class: OTHER
First posted: 2007-07-16
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a recent prospective study evaluating the efficacy of 1700 mg/day metformin as first-line approach for infertile anovulatory patients with PCOS, we identified predictors for metformin efficacy. Our analysis demonstrated that body mass index (BMI) and insulin resistance were the strongest predictors for both ovulation and pregnancy. In particular, adjusting the data for insulin resistance, a trend in reduced effectiveness was observed with increasing BMI. On the other hand, adjusting the data for BMI, a trend in improved efficacy was detected for higher insulin resistance degrees.

To date, no dose-finding study is currently available in literature evaluating the best dose of metformin to administer. In addition, very few data regarding the best protocol for metformin treatment also are available. However, in order to reduce drug-related side effects incidence due to start-up syndrome, metformin is generally administrated with meals at incremental weekly doses until the maximum dosage ranging from 500 to 2550 mg daily; the doses are reduced if side effects appear. This commonly accepted protocol has not been supported by scientific evidences.

The aim of the present study will be to evaluate in a clinical setting the compliance, the safety and the effectiveness of two schedules for metformin administration in infertile anovulatory PCOS patients.

Detailed description: Infertile anovulatory PCOS eligible patients will be enrolled and randomly allocated to receive tailored (tailored group) or non-tailored metformin treatment (non-tailored group).

Tailored metformin treatment will consist of incremental doses regimen starting from a dosage of 850 mg daily (one tablet daily) with a weekly increase up to 2550 mg daily (three tablets daily). The dosage of metformin will be reduced according to the appearance of serous or affecting compliance drug-related side effects. Conversely, non-tailored metformin treatment consisted of fixed doses regimen of 850 mg twice daily. For both groups, the treatment will be of six months.

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.

Eligibility criteria: Inclusion Criteria:

* Polycystic ovary syndrome (using NIH criteria)
* Anovulatory infertility (using WHO criteria)

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
* Previous use of ovulation induction agents
* 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

Primary outcomes:
measure: Ovulation rate
Secondary outcomes:
measure: Adverse events
measure: Adherence rate
measure: Pregnancy rate
measure: Abortion rate
measure: Live-birth rate
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: Pugliese Hospital
state: Catanzaro, CZ
Study officials:
affiliation: Department of Obstetrics & Gynecology, University "Magna Graecia" of Catanzaro
name: Stefano Palomba, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Endocrinology, University "Federico II" of Naples
name: Francesco Orio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Obstetrics & Gynecology, University "Federico II" of Naples
name: Achille Tolino, MD
role: PRINCIPAL_INVESTIGATOR
References: