Last updated: 11/07/2018 05:32:49

Birth defects associated with exposure to Lamotrigine in pregnancy (EUROCAT)

GSK study ID
113038
See study documents
Clinicaltrials.gov ID
NCT01055327
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Monitoring of specific birth defects associated with exposure to Lamotrigine in pregnancy through the EUROCAT network
Trial description: In 2007 a case control study was completed within the EUROCAT European network of congenital anomaly registers to test the hypothesis that first trimester lamotrigine monotherapy exposure is associated with an increased risk of isolated oral clefts. This study found no statistically significant increased risk of oral clefts compared with other defects following lamotrigine exposure in the uterus. The EUROCAT Antiepileptic Drug (AED) Database, established for the original case control study in 2007, will now be expanded to include an additional five to six years worth of data. These data will provide greater power to investigate the risk of isolated oral clefts, specific cleft types and potential associations with additional specific malformation types (e.g. neural tube defects). Data on cases of isolated oral clefts registered between 1993 and 2012 will be extracted from EUROCAT member registers meeting set inclusion criteria (ensuring completeness of outcome and exposure data). The primary comparison group will include all non oral cleft, non chromosomal malformations as the registers do not collect data on non malformed infants. This study will also be powered to include a second control group of chromosomal malformations, very unlikely to be associated with medication exposure. Data on exposure to anti-epileptic drugs (AEDs) during the first trimester of pregnancy will be extracted along with other key covariates including age of mother, history of epilepsy and gestational age of the infant. Primary analyses, using logistic regression, will compare the lamotrigine monotherapy versus no AED use across case and control groups and a secondary analysis will compare lamotrigine monotherapy versus other AED monotherapy (with and without valproate). Data will also be monitored for patterns of lamotrigine exposure across additional specific malformation groups of interest.
Primary purpose:
Not applicable
Trial design:
Not applicable
Masking:
Not applicable
Allocation:
Not applicable
Primary outcomes:

Non chromosomal, non monogenic, isolated oral clefts

Timeframe: Retrospective case control study. All isolated oral cleft malformations registered on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.

Secondary outcomes:

Non oral cleft, non chromosomal malformations

Timeframe: Retrospective case control study. All non oral cleft, non chromsomal malformations recorded on congenital malformation registers participating in EUROCAT anti-epileptic drug database extracted irrespective of diagnosis timing pre or post-natal.

All chromosomal malformations

Timeframe: This is a retrospective case control study. All chromosomal malformations recorded on congenital malformation registers participating in the EUROCAT anti-epileptic drug database will be extracted irrespective of timing of diagnosis pre- or post natally.

Interventions:
  • Drug: Lamotrigine monotherapy
  • Drug: No anti-epileptic drug exposure
  • Drug: Non lamotrigine anti-epileptic drug monotherapy
    • Enrollment:
    1
    Primary completion date:
    Not applicable
    Observational study model:
    Case-Control
    Time perspective:
    Retrospective
    Clinical publications:
    Dolk H, Wang H, Loane M, et al. Lamotrigine use in pregnancy and risk of orofacial cleft and other congenital anomalies. Neurology. 2016;May 3;86(18):1716-25.
    Medical condition
    Epilepsy
    Product
    lamotrigine
    Collaborators
    Not applicable
    Study date(s)
    May 2009 to December 2013
    Type
    Observational
    Phase
    Not applicable

    Participation criteria

    Sex
    Female & Male
    Age
    Not applicable
    Accepts healthy volunteers
    No
    • Individual population-based registers within EUROCAT are eligible to participate if:
    • Anti-epileptic drug exposure is recorded for at least 3 per 1000 malformed infants/fetuses (figures below this threshold indicate potential under reporting of medication exposure).
    • As above
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Individual population-based registers within EUROCAT are eligible to participate if: -Anti-epileptic drug exposure is recorded for at least 3 per 1000 malformed infants/fetuses (figures below this threshold indicate potential under reporting of medication exposure). -Specific drug names or complete 7 digit Anatomical Therapeutic Chemical (ATC) classification codes are available for at least 80% of AED exposed infants/fetuses.
    Exclusion criteria:
    • As above

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Refer to study documents

    Recruitment status
    Study complete
    Actual primary completion date
    Not applicable
    Actual study completion date
    2013-31-12

    Plain language summaries

    Not applicable. GSK’s transparency policy provides for Plain Language Summaries for Interventional studies.

    Additional information about the trial

    Not applicable
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