- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01165255
Bupropion and Specific Cardiovascular Malformations
June 6, 2017 updated by: GlaxoSmithKline
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.
Study Overview
Status
Completed
Conditions
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.
Study Type
Observational
Enrollment (Actual)
7005
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 49 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
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.
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
|
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.
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.
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
As performed previously, medical and prescription claims data was assembled and the outcomes of infants in the first 9 months of life were evaluated
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2010
Primary Completion (Actual)
December 1, 2010
Study Completion (Actual)
December 1, 2010
Study Registration Dates
First Submitted
July 1, 2010
First Submitted That Met QC Criteria
July 15, 2010
First Posted (Estimate)
July 19, 2010
Study Record Updates
Last Update Posted (Actual)
June 7, 2017
Last Update Submitted That Met QC Criteria
June 6, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Mood Disorders
- Depressive Disorder
- Congenital Abnormalities
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Dopamine Uptake Inhibitors
- Bupropion
- Antidepressive Agents
Other Study ID Numbers
- 114592
- EPI40642 (Other Identifier: GSK)
- WEUSKOP4894 (Other Identifier: GSK)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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