Lamotrigine Pregnancy Registry (LAM05)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01064297
First received: January 28, 2010
Last updated: February 21, 2013
Last verified: February 2013
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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.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.
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
Affective Disorders, Psychotic
Mental Disorders
Mood Disorders
Anticonvulsants
Lamotrigine
Valproic Acid
Antimanic Agents
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sodium Channel Blockers
Therapeutic Uses
Tranquilizing Agents
Voltage-Gated Sodium Channel Blockers

ClinicalTrials.gov processed this record on October 29, 2014