Birth Defects Associated With Exposure to Lamotrigine in Pregnancy (EUROCAT)

September 29, 2014 updated by: GlaxoSmithKline

Monitoring of Specific Birth Defects Associated With Exposure to Lamotrigine in Pregnancy Through the EUROCAT Network

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Actual)

1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All infants/fetuses with congenital malformations registered on EUROCAT anti-epileptic drug database between 1995 and 2012 (start date depends on date of lamotrigine registration in country of participating register).

EUROCAT is a European network of population-based congenital anomaly registers for surveillance. EUROCAT surveys 1.5 million births per year covering 29% of births in EU Member States.

In 2007, 19 population-based congenital malformation registers within EUROCAT participated in an initial study of the association of lamotrigine exposure in pregnancy and the risk of isolated oral clefts. These registries covered at least part of the population of Austria, Belgium, Croatia, Denmark, Finland, France, Germany, Ireland, Italy, Malta, Norway, Poland, Spain, Switzerland and Wales.

It is anticipated, that if these registers participate in the current study, the study will cover 8 million births and 200,000 congenital malformation registrations between 1995 and 2012.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Infants/foetuses w/malformations registered in EUROCAT network
Pregnancies resulting in foetus/infant with malformation registered through participating registers within the EUROCAT network
Drug: Lamotrigine monotherapy
Exposure to lamotrigine monotherapy in the first trimester of pregnancy (time period from first day of menstrual period to 12th week of gestation).
Drug: No anti-epileptic drug exposure
No exposure to anti-epileptic drugs in the first trimester of pregnancy (time period from first day of menstrual period to 12th week of gestation).
Drug: Non lamotrigine anti-epileptic drug monotherapy
Exposure to non lamotrigine monotherapy (with or without valproate) during the first trimester of pregnancy (time period from the first day of the menstrual period to the 12th week of gestation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Non chromosomal, non monogenic, isolated oral clefts
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Time Frame
Non oral cleft, non chromosomal malformations
Time Frame: 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.
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
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

January 21, 2010

First Submitted That Met QC Criteria

January 21, 2010

First Posted (Estimate)

January 25, 2010

Study Record Updates

Last Update Posted (Estimate)

October 1, 2014

Last Update Submitted That Met QC Criteria

September 29, 2014

Last Verified

September 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 113038

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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