Lamotrigine Pregnancy Registry (LAM05) - Full Text View

Purpose

Antiepileptic drugs (AEDs) are not indicated for use in pregnancy. However, women with epilepsy, and other approved indications including bipolar disorder, may require or be unintentionally exposed to AEDs during pregnancy. Prior to an AED being marketed there are few data available on drug safety in pregnancy: data from animal models may not translate directly to humans and pregnant women are routinely excluded from clinical trials. The International Lamotrigine Pregnancy Registry was established by GlaxoSmithKline (GSK) in 1992 to monitor the safety of lamotrigine during pregnancy.

Condition	Intervention
Epilepsy Bipolar Disorder	Drug: Lamotrigine monotherapy Drug: Lamotrigine polytherapy including valproate Drug: Lamotrigine polytherapy without valproate

Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	Lamotrigine Pregnancy Registry (LAM05)

Resource links provided by NLM:

Genetics Home Reference related topics: pyridoxal 5'-phosphate-dependent epilepsy

MedlinePlus related topics: Bipolar Disorder Epilepsy

Drug Information available for: Valproic acid Valproate sodium Divalproex sodium Lamotrigine

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy [ Time Frame: Although reports and diagnoses of major congenital malformations are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of live births, fetal deaths, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine monotherapy. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs.
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported following assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of live births, fetal deaths, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine polytherapy with valproate. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs.
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported following assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of live births, fetal deaths with pregnancy loss occurring >=20 weeks gestation, induced abortions, and spontaneous pregnancy losses were recorded according to the time at which women were first exposed to lamotrigine polytherapy without valproate. Due to inconsistent identification of major congenital malformations (MCMs) among spontaneous losses, no comment is made concerning the presence or absence of MCMs. Although birth defects may not have been reported, they cannot be ruled out.
Number of Infants With Major Congenital Malformations by Earliest Trimester of Exposure to Lamotrigine Monotherapy [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
Among lamotrigine monotherapy exposures: live births, fetal deaths, induced abortions with birth defects, and live births without defects. Due to the likelihood of inconsistent identification of birth defects among spontaneous losses, fetal deaths, and induced abortions without reported birth defects, these offspring were not included in analyses.
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy With Valproate [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported following assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy with valproate.
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy Without Valproate [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported following assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy without valproate.
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of infants with the reported MCM following first trimester lamotrigine monotherapy exposure were counted. Registry personnel contacted the enrolling physician to obtain information on the pregnancy outcome, lamotrigine dosing and duration of exposure, and use of concomitant antiepileptic drugs during pregnancy.
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy With Valproate According to Dose of Lamotrigine Received [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy with valproate were counted.
Number of Infants With the Indicated Major Congenital Malformations Following First Trimester of Exposure to Lamotrigine Polytherapy Without Valproate According to Dose of Lamotrigine Received [ Time Frame: Although reports and diagnoses of MCMs are accepted up to six years after the birth, the majority of malformations are reported after assessments made in the delivery room or shortly after birth ] [ Designated as safety issue: No ]
The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy without valproate were counted.

Enrollment:	3416
Study Start Date:	November 2001
Study Completion Date:	July 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Women exposed to lamotrigine during pregnancy	Drug: Lamotrigine monotherapy Lamotrigine monotherapy Drug: Lamotrigine polytherapy including valproate Lamotrigine polytherapy including valproate Drug: Lamotrigine polytherapy without valproate Lamotrigine polytherapy without valproate

Show Detailed Description

Eligibility

Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Women exposed to lamotrigine during pregnancy anywhere in the world.

Criteria

Inclusion Criteria:

Women exposed in utero to lamotrigine (as monotherapy or in a polytherapy combination) during pregnancy. Exposure can occur at any time during pregnancy, though exposure in the first trimester is of primary interest.
Pregnancies exposed to lamotrigine and reported before the outcome of the pregnancy is known (prospective reporting). Ideally exposed pregnancies are registered prior to prenatal testing, but only those pregnancies enrolled after prenatal testing has diagnosed a birth defect are excluded.
Retrospectively reported exposures (i.e. exposures registered once the pregnancy outcome is known) are included in the registry, but are considered descriptively and are not included in risk analyses.

Exclusion Criteria:

Retrospectively reported exposures (i.e. exposures registered once the pregnancy outcome is known) are included in the registry, but are reviewed separately and descriptively. These are not included in risk analyses.
Patient reported exposures and outcomes that are not verified by a healthcare provider.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064297

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

Publications:

Cunnington M, Ferber S, Quartey G; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Effect of dose on the frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study. Epilepsia. 2007 Jun;48(6):1207-10. Epub 2007 Mar 22.

Cunnington, M.C., Tennis P., and The International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Pregnancy Outcomes over 11 years of monitoring in the International Lamotrigine Pregnancy Registry. Neurology. 2005. 64: 955-60.

Cunnington MC. The International Lamotrigine pregnancy registry update for the epilepsy foundation. Epilepsia. 2004 Nov;45(11):1468. No abstract available.

Tennis P,. Eldridge R., and The International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Preliminary results on pregnancy outcomes in women using lamotrigine. Epilepsia. 2002; 43(10): 1161-7.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01064297 History of Changes
Other Study ID Numbers:	112913, 105905, EPI40048
Study First Received:	January 28, 2010
Results First Received:	June 14, 2010
Last Updated:	February 21, 2013
Health Authority:	United Kingdom: No Health Authority

Keywords provided by GlaxoSmithKline:

Pregnancy registry
Major congenital malformations
Pregnancy outcomes

Pregnancy
First trimester
Lamotrigine

Additional relevant MeSH terms:

Bipolar Disorder
Epilepsy
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses

Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Calcium Channel Blockers
Membrane Transport Modulators
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 16, 2013