Bupropion & Cardio Birth Defect (Slone)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01597661
First received: February 2, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

Bupropion is a unique drug that is used both to treat depression and as an aid in smoking cessation. In 2008, the final report from the Bupropion pregnancy registry described 24 congenital malformations among the 675 women exposed to bupropion in the first trimester of pregnancy. Of these, 9 had congenital heart disease of varying severity, including a number of infants with ventricular septal defects (VSDs); of note, 2 of these 9 had coarctation of the aorta. More recently, Alwan et al, in an analysis of data from the Centers for Disease Control and Prevention's case-control National Birth Defects Prevention Study, reported an increased risk of left outflow tract heart defects, a subgroup of cardiac malformations that includes coarctation of the aorta and hypoplastic left heart syndrome.

Data from the Slone Epidemiology Center Birth Defects Study will be used to test these observations. The outcomes of primary interest will include those hypothesized to be associated with bupropion in recent studies: left outflow tract defects considered as a group. Coarctation of the aorta and hypoplastic left heart syndrome will also be examined separately. All infants with congenital heart defects are further classified into subgroups that are embryologically meaningful, including left outflow tract defects. In secondary analyses, other heart defect classes for which there are adequate numbers of cases will be evaluated.


Condition Intervention
Depressive Disorder
Drug: Exposure to any bupropion during the first trimester
Drug: Exposure to bupropion alone during the first trimester
Other: Referent group: no exposure to any anti-depressant or anti-smoking drug during pregnancy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Retrospective
Official Title: Bupropion and Cardiac Birth Defects (Slone Epidemiology Center)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Diagnosis of left outflow tract defects [ Time Frame: Within 6 months of delivery ] [ Designated as safety issue: Yes ]
  • Diagnosis of coarctation of the aorta [ Time Frame: Within 6 months of delivery ] [ Designated as safety issue: Yes ]
  • Diagnosis of hypoplastic left heart syndrome [ Time Frame: Within 6 months of delivery ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Diagnosis of other congenital heart defects [ Time Frame: Within 6 months of delivery ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: September 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Malformed and population-based sample of non-malformed infants
Infants with any of a wide range of malformations are identified at tertiary care and birth hospitals in four study centers (Boston, Philadelphia, Toronto, San Diego) using approaches that include reviewing lists of discharge diagnoses available in medical records; contacting newborn nursery and/or labor and delivery rooms; reviewing admission/discharge lists; and reviewing clinic and surgical logs. A population-based random sample of non-malformed newborns in Massachusetts is also included. Information gathered on each subject includes name, address, telephone number, diagnostic information, and date of birth.
Drug: Exposure to any bupropion during the first trimester

The primary exposure group will be: any exposure to bupropion during the time period from 28 days prior to the last menstrual period through the fourth lunar month. The use of bupropion in combination with other anti-depressants, exposure to SSRI anti-depressants, and exposure to non-SSRI anti-depressants, including tricyclic anti-depressants, during this time period will be explored.

Mothers of identified infants are contacted within 6 months of delivery and invited to participate in the study by completing a telephone interview, conducted by trained study nurses. The interview addresses demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking, alcohol, and caffeine consumption, occupational exposures, and dietary intake. Exposure information is obtained directly from the mother in response to questions that focus both on indications for medication use and on medications themselves.

Drug: Exposure to bupropion alone during the first trimester

The secondary exposure group will be: bupropion exposure alone during the time period from 28 days prior to the last menstrual period through the fourth lunar month.

Mothers of identified infants are contacted within 6 months of delivery and invited to participate in the study by completing a telephone interview, conducted by trained study nurses. The interview addresses demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking, alcohol, and caffeine consumption, occupational exposures, and dietary intake. Exposure information is obtained directly from the mother in response to questions that focus both on indications for medication use and on medications themselves.

Other: Referent group: no exposure to any anti-depressant or anti-smoking drug during pregnancy

The referent group will be defined as no exposure to any anti-depressant or anti-smoking drug at any time from 28 days prior to the last menstrual period through the end of pregnancy.

Mothers of identified infants are contacted within 6 months of delivery and invited to participate in the study by completing a telephone interview, conducted by trained study nurses. The interview addresses demographic, reproductive, and medical factors; medication and vitamin use; cigarette smoking, alcohol, and caffeine consumption, occupational exposures, and dietary intake. Exposure information is obtained directly from the mother in response to questions that focus both on indications for medication use and on medications themselves.


  Eligibility

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

The primary focus of the Slone Epidemiology Center Birth Defects Study (BDS) case-control surveillance is to identify the risks and safety of marketed drugs taken by pregnant women. Infants with any of a wide range of malformations are identified at tertiary care and birth hospitals in four study centers (Boston, Philadelphia, Toronto, San Diego) using approaches that include reviewing lists of discharge diagnoses available in medical records; contacting newborn nursery and/or labor and delivery rooms; reviewing admission/discharge lists; and reviewing clinic and surgical logs. Information gathered on each subject includes name, address, telephone number, diagnostic information, and date of birth. Beginning in 1992, the BDS also included mothers of non-malformed infants: initially these infants were identified exclusively at study hospitals, but in 1998, they expanded their normal newborn capability by obtaining a population-based random sample of newborns in Massachusetts.

Criteria

Inclusion Criteria:

  • Subjects with congenital heart defects who are born within the catchment areas of the 4 study centers
  • A sample of nonmalformed infants born at participating hospitals
  • Subjects who were interviewed in 1992 or later
  • Women who complete the study interview within 6 months of the infant's birth

Exclusion Criteria:

  • Infants with chromosomal anomalies
  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: NCT01597661

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01597661     History of Changes
Other Study ID Numbers: 115433, WEUSKOP5344, EPI40662
Study First Received: February 2, 2012
Last Updated: July 3, 2014
Health Authority: United States: No Health Authority

Keywords provided by GlaxoSmithKline:
first trimester
left outflow tract obstruction
Bupropion
cardiovascular malformation
antidepressants
pregnancy
cardiovascular defect
congenital malformation

Additional relevant MeSH terms:
Congenital Abnormalities
Depressive Disorder
Depression
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Bupropion
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antidepressive Agents, Second-Generation
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 26, 2014