Trial document




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  DRKS00007621

Trial Description

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Title

Pregnancy outcome after first-trimester exposure to metformin: the experience of the Berlin institute for clinical teratology and drug risk assessment in pregnancy

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

Metformin is primarily used as an antidiabetic drug. In addition, benefits in the treatment of fertility problems, which were caused by a polycystic ovary syndrome (PCOS), have been described. Although various studies on the use of metformin during pregnancy have already been performed, data regarding safety of use in the first trimester are still insufficient. The proposed study will contribute significantly to the safety assessment of the use of metformin in early pregnancy and offer new treatment strategies.
Patients with metformin therapy in the first trimester of pregnancy are compared with patients without metformin therapy.

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Brief Summary in Scientific Language

Metformin is a biguanide and is primarily used as medication of choice for the treatment of type 2 diabetes, in particular in overweight and obese patients. Metformin mainly decreases hepatic glucose production by interacting with different pathways but the complete mechanism of action remains unclear. In recent years, the use of metformin during pregnancy increased. Though it is not licensed for use during pregnancy, certain advantages over insulin therapy are discussed for the treatment of gestational diabetes and preexisting type 2 diabetes. For women affected by a polycystic ovary syndrome (PCOS), metformin is used to treat reduced fertility and prevent further problems associated with PCOS during pregnancy. Possible clinical benefits are the improvement of insulin resistance, the prevention of preterm delivery and a decrease in the rate of spontaneous abortions, respectively. Although it is generally believed that metformin does not increase the risk of congenital malformations, robust data to confirm the safety are still lacking. Only a minority of the studies conducted to date specifically addressed the malformation risk after metformin exposure. To identify drug-specific effects on pregnancy outcome an appropriate control group is of particular importance. A large number of patients treated with metformin are obese with a higher risk for adverse pregnancy outcome. Based on these specific conditions, body mass index (BMI) and additional risk factors should be considered when calculating the teratogenic risk. Improved knowledge of its safety during pregnancy is an important precondition for recommending metformin as a treatment option for women with endocrine disorders.

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Organizational Data

  •   DRKS00007621
  •   2015/08/27
  •   [---]*
  •   yes
  •   Approved
  •   EA4/081/14, Ethik-Kommission der Charité -Universitätsmedizin Berlin-
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Secondary IDs

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Health Condition or Problem studied

  •   congenital malformations/spontaneous abortions after intrauterine metformin exposure
  •   Q89.9 -  Congenital malformation, unspecified
  •   O03 -  Spontaneous abortion
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Interventions/Observational Groups

  •   Prospectively ascertained pregnancies with metformin exposure in the first trimester; existing data from the archive of the isntitute are analyzed for this study
  •   Control group: Prospectively ascertained pregnancies without any metformin therapy; the control group will be frequency-matched to the study group according to BMI and year of ascertainment; existing data from the archive of the institute are analyzed for this study
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Characteristics

  •   Non-interventional
  •   Observational study
  •   Non-randomized controlled trial
  •   Open (masking not used)
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  •   Other
  •   Prognosis
  •   Parallel
  •   N/A
  •   Yes
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Primary Outcome

Rate of major congenital malformations (detection up to 8 weeks after birth) and of spontaneous fetal loss

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Secondary Outcome

premature birth, birth weight, and pregnancy complications

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
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Recruitment

  •   Planned
  •   2015/09/15
  •   1500
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Female
  •   no minimum age
  •   no maximum age
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Additional Inclusion Criteria

Both cohorts: prospectively ascertained pregnancies, i.e. outcome of pregnancy is unknown at the time of contact to the study centre; study cohort: metformin exposure during the first trimester of pregnancy; control cohort: control group without metformin therapy

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Exclusion Criteria

malignancies, exposure to established teratogens (lenalidomide, carbamazepine, methotrexate, mycophenolate, phenobarbital, phenprocoumon, phenytoin, retinoids (acitretin, adapalen, isotretinoin, tazaroten, tretinoin), thalidomide, topiramate, warfarin) or fetotoxicants (angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II receptor antagonists) after the first trimester; valproaic acid-exposed pregnancies will be evaluated separately (patients may be prone to PCOS)

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Addresses

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    • Pharmakovigilanz- und Beratungszentrum für EmbryonaltoxikologieCharité - Universitätsmedizin Berlin
    • Mr.  Prof. Dr.  Christof  Schaefer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanz- und Beratungszentrum für EmbryonaltoxikologieCharité - Universitätsmedizin Berlin
    • Mr.  Prof. Dr. med.  Christof  Schaefer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    • Pharmakovigilanz- und Beratungszentrum für EmbryonaltoxikologieCharité - Universitätsmedizin Berlin
    • Mr.  Prof. Dr. med.  Christof  Schaefer 
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Charité - Universitätsmedizin Berlin
    • Augustenburger Platz 1
    • 13353  Berlin
    • Germany
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    •   [---]*
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    • Deutsche Diabetes Gesellschaft
    • Reinhardtstr. 31
    • 10117  Berlin
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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