Butoconazole use in pregnancy: population-based case-control studies on adverse pregnancy outcomes in Hungary (study protocol RGD-77425)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  BUTOCONAZOLE

  MICONAZOLE

  CLOTRIMAZOLE

  NYSTATIN

  METRONIDAZOLE

  DICLOFENAC

  IBUPROFEN

  ISOTRETINOIN

  VALPROIC ACID

  CARBAMAZEPINE
• Medical condition to be studied:
  Congenital anomaly

  Abortion spontaneous

  Stillbirth

  Live birth

  Ectopic pregnancy

  Low birth weight baby

  Pregnancy

  Maternal exposure during pregnancy

Population studied

• Short description of the study population:
  All pregnancy outcomes reported to the National Healthcare Fund (OEP) between 01 January 2005 and 31 December 2011 who were exposed to butaconazole.
• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Children (2 to < 12 years)

  Adults (18 to < 46 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  1100000

Study design details

• Main study objective:
  To confirm the results of the F. Rosa study described in (Briggs 2011), i.e. to confirm the lack of teratogenic potential of locally applied butoconazole in humans. In addition, a dedicated case-control analysis is planned on the risk of spontaneous abortion in butoconazole exposed pregnancies. Other gynecologic anti-infectives are also included in these analyses for comparison.
• Outcomes:
  The study has two co-primary objectives:- to evaluate butoconazole treatment as a potential teratogenic risk factor in a population-based case-control study in Hungary, based on the OEP database,- to evaluate butoconazole treatment as a potential risk factor of spontaneous abortion in a population-based case-control study in Hungary, based on the OEP database. - to evaluate other gynecology anti-infectives (clotrimazole, miconazole, nystatin, metronidazole) as risk factors of teratogenicity or spontaneous abortion for comparative assessment, in the same setting,- to collect epidemiologic data on pregnancy outcomes in butoconazole exposed pregnancies (in compliance with EMEA/CHMP/313666/2005).
• Data analysis plan:
  The planned analyses comprise descriptive statistics of drug exposure in pregnancies with different pregnancy outcomes, analysis of birth weight in unexposed and drug-exposed pregnancies, and case-control studies on spontaneous abortion and congenital abnormalities considering a range of confounding factors and sensitivity analyses. Crude and adjusted odds ratios will be calculated for both of the co-primary outcomes, with several sensitivity analyses and several alternative definitions of relevant drug exposure periods. Results of all these analyses will be evaluated together, to allow for robust conclusions. Any positive finding in these analyses will be interpreted in the context of similar findings with therapeutic comparators.

Documents

Study results

Final Report_20161121_signed_Vol1

Protocol Amendment2_final_clean

Study report

15_1_8

Final Report_20161121_signed_Vol2

Final Report_20161121_signed_Vol3

Study, other information

approval-for-the-clinical-trial-GYEMSZI

butoconazole-nitrate-approval-modification

Final Report_20161121_signed_Vol2.pdf

Final Report_20161121_signed_Vol3.pdf