EpilepsyNCT01064297

Lamotrigine Pregnancy Registry (LAM05)

An observational study of Epilepsy and Bipolar Disorder, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Any age, women only
Conditions the study is for: Epilepsy, Bipolar Disorder
What is being tested?: Lamotrigine monotherapy, Lamotrigine polytherapy including valproate and Lamotrigine polytherapy without valproate
How many people: 3,416 participants
Where: No sites listed yet
Study dates: Nov 2001to Jul 2010
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
Women only
No healthy volunteers
Child, Adult, Older adult

Study population: Women exposed to lamotrigine during pregnancy anywhere in the world.

Who may be able to join

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.

Who cannot join

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.

About this study

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.

Read the detailed description

The International Lamotrigine Pregnancy Registry aims to assess whether there is a substantial increase in the risk of major congenital malformations (MCMs) following in utero exposure to lamotrigine. Exposure during the first trimester is of primary interest as this represents the period of organogenesis. The Registry is a primarily prospective enrolment and follow-up study. Patients exposed to lamotrigine during pregnancy are enrolled, on a voluntary basis, by their healthcare provider. Enrolment is encouraged early in pregnancy and if possible prior to any prenatal testing. The healthcare provider provides initial information concerning patient demographics; details of the pregnancy including the estimated delivery date and results of any prenatal testing; and the timing, duration and dosage of lamotrigine exposure in pregnancy. The registry accepts exposure reports from anywhere in the world. Within the United States (US) the healthcare provider can contact the registry using a toll free number. Outside of the US enrolments are made through the GlaxoSmithKline local operating company.

Close to the estimated date of delivery the healthcare provider is contacted by the Registry to provide follow up information concerning the pregnancy outcome (live or still birth, spontaneous or induced abortion), the presence or absence of a MCM, and the history of exposure to lamotrigine as well other antiepileptics and antipsychotics during pregnancy. Up to six attempts are made to contact the healthcare provider to obtain pregnancy outcome information. After six attempts, the record is closed as lost to follow up. Pregnancy outcomes are classified as outcomes with MCMs, outcomes without MCMs and spontaneous abortions. The outcomes with and without MCMs are further classified as live births, stillbirths/fetal deaths and induced abortions. Spontaneous abortions are reported separately due to potential for inconsistent identification of malformations in that situation.

It is beyond the scope of the Registry to consistently access pediatric evaluations and medical records. For this reason the main outcome is restricted to major congenital malformations that are external and recognizable in the delivery room or shortly after birth. To provide consistency, reported congenital malformations are classified as major or minor according to criteria used by the Centers for Disease Control and Prevention (CDC)'s Metropolitan Atlanta Congenital Defects Program (MACDP). All malformation reports are reviewed and classified by a paediatrician from the CDC and further information is requested as necessary.

Analyses are restricted to prospectively enrolled pregnancies (enrolment prior to knowledge of the birth outcome). Retrospectively enrolled pregnancies are reviewed for patterns of defect types, but are not included in formal analyses as retrospective reporting can be biased towards more unusual and severe outcomes and are less likely to be representative of the general population experience. The proportion of infants with MCMs among prospectively reported exposures is calculated as: the total number of outcomes with major birth defects (number of outcomes with major birth defects + the number of live births without defects).

Chromosomal malformations are reported descriptively, but are not included in the numerator as it is very unlikely that they are associated with drug exposure during pregnancy. All spontaneous pregnancy losses, as well as induced abortions and fetal deaths without reported defects, are excluded from the denominator due to the potential for inconsistent identification of malformations in those situations. The 95% confidence intervals (CIs) for risk estimates are calculated using exact methods based on the binomial distribution.

Analyses are stratified according to trimester of exposure (with the second trimester starting at week 14 and the third trimester at week 28 of gestation) and by exposure group (lamotrigine monotherapy, lamotrigine polytherapy including valproate and lamotrigine polytherapy without valproate).

The registry does not have an internal comparator group, but descriptive comparisons are made with MCM rates from general population studies in the literature and from other ongoing AED pregnancy registries. Prospective reports are also reviewed to detect any unusual patterns of malformation types that may warrant further investigation. The data from the International Lamotrigine Pregnancy Registry are reviewed, and conclusions developed, by an independent scientific advisory committee. A semi-annual interim report summarizing aggregate data is provided to disseminate information on a regular basis.

Conditions: Epilepsy, Bipolar Disorder
Being tested: Lamotrigine monotherapy, Lamotrigine polytherapy including valproate, Lamotrigine polytherapy without valproate
Keywords: Pregnancy registry, Major congenital malformations, Pregnancy outcomes, Pregnancy, First trimester, Lamotrigine
Medical subject headings: Epilepsy, Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Lamotrigine monotherapyDrug
Lamotrigine monotherapy
Lamotrigine polytherapy including valproateDrug
Lamotrigine polytherapy including valproate
Lamotrigine polytherapy without valproateDrug
Lamotrigine polytherapy without valproate

Study groups in NCT01064297
Study group	Role	What they receive
Women exposed to lamotrigine during pregnancy		Not described Receives: Drug: Lamotrigine monotherapy; Drug: Lamotrigine polytherapy including valproate; Drug: Lamotrigine polytherapy without valproate

What is being measured

The primary outcome is the main question the study is designed to answer.

Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Monotherapy
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.
Measured: 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
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy With Valproate
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.
Measured: 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
Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate
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.
Measured: 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
Number of Infants With Major Congenital Malformations by Earliest Trimester of Exposure to Lamotrigine Monotherapy
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.
Measured: 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
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy With Valproate
The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy with valproate.
Measured: 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
Number of Infants With Major Congenital Malformations (MCMs) by Earliest Trimester of Exposure to Lamotrigine Polytherapy Without Valproate
The number of infants with major congenital malformations were counted and are presented by earliest trimester of exposure to lamotrigine polytherapy without valproate.
Measured: 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
Number of Infants With the Indicated Major Congenital Malformations Following the First Trimester of Exposure to Lamotrigine Monotherapy According to Dose Received
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.
Measured: 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
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
The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy with valproate were counted.
Measured: 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
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
The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy without valproate were counted.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2001Jul 2010

First posted8 Feb 2010 (estimated)
Study startNov 2001
Primary completionJul 2010
Study completionJul 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (6)Papers the sponsor has linked to this study.
Other trials for EpilepsyStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 3,416 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01064297
Sponsor's protocol ID: 112913
Other IDs: 105905, EPI40048
Status last verified: Feb 2013
First submitted: 28 Jan 2010
Last updated: 25 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Cunnington MC, Weil JG, Messenheimer JA, Ferber S, Yerby M, Tennis P. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology. 2011 May 24;76(21):1817-23. doi: 10.1212/WNL.0b013e31821ccd18.
PubMed 21606453
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. doi: 10.1111/j.1528-1167.2007.01021.x. Epub 2007 Mar 22.
PubMed 17381445
Cunnington M, Tennis P; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Lamotrigine and the risk of malformations in pregnancy. Neurology. 2005 Mar 22;64(6):955-60. doi: 10.1212/01.WNL.0000154515.94346.89.
PubMed 15781807
Cunnington MC. The International Lamotrigine pregnancy registry update for the epilepsy foundation. Epilepsia. 2004 Nov;45(11):1468. doi: 10.1111/j.0013-9580.2004.451105.x. No abstract available.
PubMed 15509254
Lamotrigine Pregnancy Registry. Interim Report 1 September 1992 through 31 March 2010. Issued July 2010. Available at: http://pregnancyregistry.gsk.com/index.html
Tennis P, Eldridge RR; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Preliminary results on pregnancy outcomes in women using lamotrigine. Epilepsia. 2002 Oct;43(10):1161-7. doi: 10.1046/j.1528-1157.2002.45901.x.
PubMed 12366730

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Lamotrigine Pregnancy Registry (LAM05)
ClinicalTrials.gov ID: NCT01064297
Acronym / sponsor ID: 112913
Conditions: Epilepsy, Bipolar Disorder
Keywords: Pregnancy registry, Major congenital malformations, Pregnancy outcomes, Pregnancy, First trimester, Lamotrigine
Study type: Observational
Recruitment status: Completed
Enrolment: 3,416 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: Nov 2001
Primary completion: Jul 2010 (actual)
Study completion: Jul 2010 (actual)
First posted: 8 Feb 2010 (estimated)
Results: Posted 11 Oct 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Women exposed to lamotrigine during pregnancy	–	Drug: Lamotrigine monotherapy, Drug: Lamotrigine polytherapy including valproate, Drug: Lamotrigine polytherapy without valproate

Who may qualify

Sex: Female only
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
Study population: Women exposed to lamotrigine during pregnancy anywhere in the world.

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (2 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Lamotrigine monotherapyLamotrigine monotherapy	Drug	Women exposed to lamotrigine during pregnancy
Lamotrigine polytherapy including valproateLamotrigine polytherapy including valproate	Drug	Women exposed to lamotrigine during pregnancy
Lamotrigine polytherapy without valproateLamotrigine polytherapy without valproate	Drug	Women exposed to lamotrigine during pregnancy

Primary outcome

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
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
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
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
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
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
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
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
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
The number of infants with the reported MCM following first trimester exposure to lamotrigine polytherapy without valproate were counted.

Results and safety

Results posted to the registry on 11 Oct 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lamotrigine Monotherapy Pregnancy Exposures	2,567	1,776
Lamotrigine Polytherapy With Valproate Pregnancy Exposures	219	171
Lamotrigine Polytherapy Without Valproate Pregnancy Exposures	630	497

Primary outcome: 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. Number. Unit: infants

Measure	First Exposure During First Trimester n = 1699	First Exposure During Second Trimester n = 95	First Exposure During Third Trimester n = 18	Unspecified Trimester of Exposure n = 5
Live Birth (Birth Defects Reported)	31	4	1	0
Fetal Death (Birth Defects Reported)	1	0	0	0
Induced Abortion (Birth Defects Reported)	3	0	0	0
Live Birth (No Birth Defects Reported)	1523	91	17	5
Fetal Death (No Birth Defects Reported)	10	0	0	0
Induced Abortion (No Birth Defects Reported)	33	0	0	0
Spontaneous Pregnancy Loss	98	0	0	0

Population analysed: Prospectively enrolled pregnancies exposed to lamotrigine monotherapy.

Primary outcome: 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. Number. Unit: infants

Measure	First Exposure During First Trimester n = 161	First Exposure During Second Trimester n = 8	First Exposure During Third Trimester n = 3	Unspecified Trimester of Exposure n = 1
Live Birth (Birth Defects Reported)	14	1	0	0
Fetal Death (Birth Defects Reported)	0	0	0	0
Induced Abortion (Birth Defects Reported)	2	0	0	0
Live Birth (No Birth Defects Reported)	134	6	3	1
Fetal Death (No Birth Defects Reported)	1	1	0	0
Induced Abortion (No Birth Defects Reported)	4	0	0	0
Spontaneous Pregnancy Loss	6	0	0	0

Population analysed: Prospectively enrolled pregnancies exposed to lamotrigine polytherapy with valproate.

Primary outcome: Birth Outcomes by Earliest Pregnancy Trimester of Exposure to Lamotrigine Polytherapy Without Valproate

Measure	First Exposure During First Trimester n = 474	First Exposure During Second Trimester n = 25	First Exposure During Third Trimester n = 3	Unspecified Trimester of Exposure n = 0
Live Birth (Birth Defects Reported)	11	0	1	–
Fetal Death (Birth Defects Reported)	0	0	0	–
Induced Abortion (Birth Defects Reported)	1	0	0	–
Live Birth (No Birth Defects Reported)	418	25	2	–
Fetal Death (No Birth Defects Reported)	3	0	0	–
Induced Abortion (No Birth Defects Reported)	19	0	0	–
Spontaneous Pregnancy Loss	22	0	0	–

Population analysed: Prospectively enrolled pregnancies exposed to the lamotrigine polytherapy without valproate

Primary outcome: 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. Number. Unit: infants

Measure	First Exposure During First Trimester n = 1558	First Exposure During Second Trimester n = 95	First Exposure During Third Trimester n = 18	Unspecified Trimester of Exposure n = 5	All Trimesters n = 1676
Value	35	4	1	0	40

First Exposure During First Trimester: Wilson Score with Continuity Correction: 2.2 (95% CI 1.6 to 3.1)
First Exposure During Second Trimester: Wilson Score with Continuity Correction: 4.2 (95% CI 1.4 to 11.0)
All Trimesters: Wilson Score with Continuity Correction: 2.4 (95% CI 1.7 to 3.3)

Population analysed: 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.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lamotrigine Monotherapy Pregnancy Exposures	35 of 1,776 (2%)	0 of 0	Not reported
Lamotrigine Polytherapy With Valproate Pregnancy Exposures	16 of 171 (9.4%)	0 of 0	Not reported
Lamotrigine Polytherapy Without Valproate Pregnancy Exposures	12 of 497 (2.4%)	0 of 0	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 21606453Cunnington MC, Weil JG, Messenheimer JA, Ferber S, Yerby M, Tennis P. Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology. 2011 May 24;76(21):1817-23. doi: 10.1212/WNL.0b013e31821ccd18.
Background: PubMed 17381445Cunnington 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. doi: 10.1111/j.1528-1167.2007.01021.x. Epub 2007 Mar 22.
Background: PubMed 15781807Cunnington M, Tennis P; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Lamotrigine and the risk of malformations in pregnancy. Neurology. 2005 Mar 22;64(6):955-60. doi: 10.1212/01.WNL.0000154515.94346.89.
Background: PubMed 15509254Cunnington MC. The International Lamotrigine pregnancy registry update for the epilepsy foundation. Epilepsia. 2004 Nov;45(11):1468. doi: 10.1111/j.0013-9580.2004.451105.x. No abstract available.
BackgroundLamotrigine Pregnancy Registry. Interim Report 1 September 1992 through 31 March 2010. Issued July 2010. Available at: http://pregnancyregistry.gsk.com/index.html
Background: PubMed 12366730Tennis P, Eldridge RR; International Lamotrigine Pregnancy Registry Scientific Advisory Committee. Preliminary results on pregnancy outcomes in women using lamotrigine. Epilepsia. 2002 Oct;43(10):1161-7. doi: 10.1046/j.1528-1157.2002.45901.x.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

An observational study of Epilepsy and Bipolar Disorder, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Oct 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01064297, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2013.