Bupropion and Specific Cardiovascular Malformations

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01165255
First received: July 1, 2010
Last updated: June 2, 2011
Last verified: June 2011
  Purpose

The study is an extension of earlier work based on a retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety (Clinical study ID WWE113694) (Cole JA, Oh KS, Chiang CC, Walker AM, Haight BR, Modell JG. Bupropion in pregnancy and the prevalence of congenital malformations Pharmacoepidemiology and Drug Safety, 2007; 16: 474-484). The cohorts developed for the earlier work consisted of all infants born to women exposed to bupropion during the estimated first trimester and outside the first trimester, and a random sample of infants born to women exposed to other antidepressants during the first trimester between 01 January 1995 and 30 September 2004. The objectives for this study include refining of both the original first trimester bupropion cohort and the original bupropion outside the first trimester cohort into mono-therapy and mono- or poly-therapy. Exposure to other antidepressants during the first trimester will also be refined into mono-therapy and mono- or poly-therapy. With input from pediatric cardiology expert, lists of specific cardiovascular malformations and malformation groupings will be created. The groupings will be created among the refined first trimester bupropion cohort as well as in two comparison cohorts of bupropion outside the first trimester and first trimester antidepressant use (mono-therapy and mono-or poly-therapy). The prevalence in each cohort will be calculated as the number of infants with a specific cardiovascular malformation divided by the number of live born infants. Prevalence will be reported per 1,000 infants. Confidence intervals will be calculated using Wilson's approximation to exact binomial intervals when the number of cases is five or greater and exact binomial intervals when the number of cases is fewer than five. The appropriateness of further calculations will be evaluated. Where numbers permit, adjusted odds ratios for specific cardiovascular groups/malformations will be calculated and if appropriate, stratified according to maternal dispensing of medications suspected to be teratogenic. The following comparisons, if numbers permit, will be performed: 1) bupropion first trimester mono-therapy cohort versus other antidepressant first trimester mono-therapy cohort; 2) bupropion first trimester mono- or poly-therapy cohort versus other antidepressant first trimester mono- or poly-therapy cohort; 3) bupropion first trimester mono-therapy cohort versus bupropion outside of first trimester mono-therapy cohort, and 4) bupropion first trimester mono- or poly-therapy cohort versus bupropion outside of first trimester mono- or poly-therapy cohort. Adjusted odds ratios will be calculated through a generalized estimated equations form of multivariate logistic regression to account for births associated with multiple infants. The same covariates identified in the original study will be included in this re-analysis. Covariates included: diagnoses of bipolar disorder and eclampsia within one year before delivery; dispensings of lithium, phenytoin, and fluconazole within one year before delivery through the end of the first trimester; and the number of physician visits within 10 to 12 months before delivery, maternal age, geographic region of the health plan, and infant gender. If generalized estimating equation form of the logistic regression model does not converge, adjusted odds ratios will be presented from a conventional multivariate logistic model. If the conventional multivariate logistic model does not converge, only the crude odds ratio will be presented.


Condition Intervention
Depressive Disorder
Pregnancy
Smoking Cessation
Drug: 3. Exposure to other antidepressants during the first trimester comparison cohort
Drug: 2. Exposure to bupropion outside the first trimester comparison cohort
Drug: 1. Exposure to bupropion during the first trimester

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Bupropion and Specific Cardiovascular Malformations

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Frequencies and prevalence estimates of specific cardiovascular malformations and malformation groupings among live infants born to women exposed to bupropion or antidepressants [ Time Frame: As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated ] [ Designated as safety issue: Yes ]

Enrollment: 7005
Study Start Date: June 2010
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Infants born to women who were exposed to antidepressants
Women ages 12 through 49 (as of delivery date) who were dispensed an antidepressant between 01 January 1995 and 30 September 2004 from the original Bupropion study.
Drug: 3. Exposure to other antidepressants during the first trimester comparison cohort
Exposure to other antidepressants during first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate dispensing of other antidepressants. Infants were classified according to maternal exposure to other antidepressants during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women who were exposed only to one type of an antidepressant ("other antidepressant monotherapy"), or more than one type of an antidepressant ("other antidepressant mono or polytherapy") during the first trimester. A woman was considered exposed if there is at least one dispensing of another antidepressant during the first trimester of pregnancy.
Drug: 2. Exposure to bupropion outside the first trimester comparison cohort
Exposure to bupropion outside the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. The comparison cohort ("bupropion exposure outside the first trimester") included women whose bupropion exposure occurred at least one month before the estimated date of conception and women whose bupropion exposure occurred after the first trimester, but before delivery. This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy") during the period outside the first trimester.
Drug: 1. Exposure to bupropion during the first trimester
Exposure to bupropion during the first trimester was classified in the original study using pharmacy claims submitted electronically to the Ingenix Research Database to indicate a dispensing of bupropion. Infants were classified according to maternal exposure to bupropion during the first trimester. The first trimester was estimated as the earliest probable conception date through 91 days (13 weeks) following the latest probable conception date (based on delivery diagnosis codes). This study will refine the exposure classifications into infants born to women, who were exposed only to bupropion ("bupropion monotherapy"), or bupropion and another type of an antidepressant ("bupropion mono-or polytherapy"). A woman was considered exposed in the first trimester if there was at least one dispensing of bupropion during the first trimester of pregnancy.

Detailed Description:

Patients were not recruited for nor enrolled in this study. This study is a retrospective observational study. Data from medical records or insurance claims databases are anonymised and used to develop a patient cohort. All diagnoses and treatment are recorded in the course of routine medical practice.

  Eligibility

Ages Eligible for Study:   12 Years to 49 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The study population will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety. 1,213 infants born to 1,140 women (1,142 pregnancies) were exposed to bupropion during the first trimester. The comparison groups consisted of 4,753 infants born to 4,617 women (4,649 pregnancies) exposed to other anti-depressants during the first trimester, and 1,049 infants born to 1,009 women (1,009 pregnancies) exposed to bupropion outside of the first trimester. All medical and prescription claims data along with dates of health plan enrollment for these women were included. The other antidepressant sample was frequency-matched to the bupropion cohort by year of birth, and was selected irrespective of exposure to specific antidepressants.

Criteria

Inclusion Criteria:

The inclusion criteria will be the same as that used previously in the retrospective epidemiologic study of infants born to women who were exposed to bupropion in their estimated first trimester of pregnancy using data from a large US health plan affiliated with i3 Drug Safety.

  • All deliveries occurring between 01 January 1995 and 30 September 2004 among women ages 12 to 49 who are members of UnitedHealthcare
  • Eligible for prescription benefits
  • Have one or more dispensings of an antidepressant during the study period
  • Continuously enrolled for at least eighteen months prior to delivery
  • Women were required to have one year of continuous health plan membership before their delivery date.
  • Women were also included when the associated infant remained on the insurance plan.

Exclusion Criteria:

  • Members who are employees of UnitedHealthcare are excluded from the Ingenix Research Database.
  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: NCT01165255

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

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01165255     History of Changes
Other Study ID Numbers: 114592, EPI40642, WEUSKOP4894
Study First Received: July 1, 2010
Last Updated: June 2, 2011
Health Authority: United States: No Health Authority

Keywords provided by GlaxoSmithKline:
congenital malformation
cardiovascular malformation
cardiovascular defect
antidepressants
pregnancy
first trimester
Bupropion
prevalence

Additional relevant MeSH terms:
Congenital Abnormalities
Depressive Disorder
Depression
Smoking
Mood Disorders
Mental Disorders
Behavioral Symptoms
Habits
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 24, 2014