Clinical trial NCT01165255: Bupropion and Specific Cardiovascular Malformations
Official title: Bupropion and Specific Cardiovascular Malformations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depressive Disorder
Pregnancy
Smoking Cessation
Keywords: congenital malformation
cardiovascular malformation
cardiovascular defect
antidepressants
pregnancy
first trimester
Bupropion
prevalence
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-07-19
Enrollment: 7005
Sex: FEMALE
Minimum age (years): 12
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

Brief summary: 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.

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 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.

Primary outcomes:
measure: Frequencies and prevalence estimates of specific cardiovascular malformations and malformation groupings among live infants born to women exposed to bupropion or antidepressants
timeFrame: As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: