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Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women (BIBS)

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ClinicalTrials.gov Identifier: NCT02188459
Recruitment Status : Completed
First Posted : July 11, 2014
Results First Posted : May 4, 2021
Last Update Posted : May 4, 2021
Sponsor:
Information provided by (Responsible Party):
Henry Kranzler, University of Pennsylvania

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Smoking
Nicotine Dependence
Intervention Drug: Bupropion
Enrollment 129
Recruitment Details Recruitment of pregnant smokers began on 10/30/2014. The study completed all treatment and follow-up phases on 1/20/2020. Pregnant smokers were recruited from maternal medicine sites in Philadelphia, PA and Newark, DE.
Pre-assignment Details  
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description

Bupropion 150 mg BID, PO for 10 weeks

Bupropion: A total of 360 participants will be randomly assigned to one of two treatment conditions: Bupropion 300 mg/day (n = 180) or placebo (n = 180). We will use small-block randomization by site (Penn). A PHQ-9 score of 10 or greater will be used to identify major depression and stratify the randomization on it. Study site (Penn) will be the second of the two stratification variables.

Placebo BID, PO for 10 weeks. The formulation appears identical to the bupropion capsules.

Bupropion: A total of 360 participants will be randomly assigned to one of two treatment conditions: Bupropion 300 mg/day (n = 180) or placebo (n = 180). We will use small-block randomization by site (Penn). A PHQ-9 score of 10 or greater will be used to identify major depression and stratify the randomization on it. Study site (Penn) will be the second of the two stratification variables.

Period Title: Overall Study
Started 64 65
Completed 61 58
Not Completed 3 7
Reason Not Completed
Lost to Follow-up             3             4
Early Termination             0             3
Arm/Group Title Placebo Bupropion Total
Hide Arm/Group Description Placebo BID, PO for 10 weeks. Bupropion 150 mg BID, PO for 10 weeks Total of all reporting groups
Overall Number of Baseline Participants 65 64 129
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 65 participants 64 participants 129 participants
28.1  (4.7) 29.0  (5.0) 28.5  (4.8)
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Female Number Analyzed 65 participants 64 participants 129 participants
65
 100.0%
64
 100.0%
129
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
35
  53.8%
32
  50.0%
67
  51.9%
White
30
  46.2%
32
  50.0%
62
  48.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 65 participants 64 participants 129 participants
65
 100.0%
64
 100.0%
129
 100.0%
Education (% High School Graduate or less)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
21
  32.3%
18
  28.1%
39
  30.2%
Annual Household Income (<40K)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
49
  75.4%
47
  73.4%
96
  74.4%
Marital Status (% Partnered)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
25
  38.5%
22
  34.4%
47
  36.4%
Depression (PHQ-9)   [1] 
Mean (Standard Deviation)
Unit of measure:  Total score
Number Analyzed 65 participants 64 participants 129 participants
4.9  (3.8) 5.4  (4.1) 5.1  (3.9)
[1]
Measure Description: The Patient Health Questionnaire (PHQ-9), is a validated 9-item self-report measure of depressive symptoms that yields a total score of 0-27 (Kroenke, Spitzer et al. 2001). A PHQ-9 score of 10 or greater was used to identify major depression. The higher the score the great the symptoms of depression.
Fagerstrom Test for Nicotine Dependence   [1] 
Mean (Standard Deviation)
Unit of measure:  Total score
Number Analyzed 65 participants 64 participants 129 participants
3.8  (1.9) 3.8  (1.9) 3.8  (1.9)
[1]
Measure Description:

Fagerstrom Test for Nicotine Dependence (FTND) (Fagerstrom and Schneider 1989) is a 6-item, self-report measure of nicotine dependence derived from the Fagerstrom Tolerance Questionnaire.

The range is from 1-8 with a higher score indicating a greater level of nicotine dependence.

Cigarettes/Day in Past 30 Days   [1] 
Mean (Standard Deviation)
Unit of measure:  Cigarettes per day
Number Analyzed 65 participants 64 participants 129 participants
7.9  (4.5) 8.0  (4.2) 7.9  (4.3)
[1]
Measure Description: Number of cigarettes smoke each day over the past 30 days was collected using the Timeline Follow-back method, combined with the exhaled carbon monoxide (CO) concentrations. Abstinence was self-reported and confirmed by a CO concentration <8 parts per million (ppm). A CO of 8 ppm or greater indicates cigarettes smoked where smoked with higher CO ppm concentration indicates that a greater number of cigarettes were smoked. Participants were assumed to be smoking if they did not provide self-report data or a breath sample at the time of measurement.
Breath CO, ppm   [1] 
Mean (Standard Deviation)
Unit of measure:  Parts per million
Number Analyzed 65 participants 64 participants 129 participants
8.3  (5.2) 9.2  (5.7) 8.8  (5.4)
[1]
Measure Description: Breath Carbon Monoxide (CO) is measured in parts per million (ppm) using a hand held breath CO analyzing device. The device measures CO in a range from 0 ppm to 25 ppm, 25 ppm being the greatest concentration of CO the device can measure. Self reported abstinence was confirmed by a breath CO concentration <8 ppm.
Total number of years smoking cigarettes   [1] 
Mean (Standard Deviation)
Unit of measure:  Totals years smoking cigarettes
Number Analyzed 65 participants 64 participants 129 participants
12.0  (5.5) 13.0  (5.1) 12.5  (5.3)
[1]
Measure Description: Participants responded to a questionnaire that queried the total number of years that they had been smoking cigarettes. More years of smoking is associated with greater severity of nicotine dependence and greater difficulty in quitting smoking.
Number of Times Quit Smoking for >24 Hours   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of times quit smoking cigarettes
Number Analyzed 65 participants 64 participants 129 participants
2.9  (2.7) 3.8  (7.0) 3.3  (5.3)
[1]
Measure Description: Participants responded to a question regarding the total number of times that they quit smoking cigarettes for a period greater than 24 hours.
Weeks of Gestational Age   [1] 
Median (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 65 participants 64 participants 129 participants
18.5  (4.6) 18.4  (4.2) 18.4  (4.4)
[1]
Measure Description: Gestational Age is measured in weeks. Only pregnant smokers who had a gestational age between 13 and 26 weeks were included in the study. Gestational age was assessed usin a method developed by the NICHD-sponsored Maternal-Fetal Medicine Units Network. The gestational age was based on the projected estimated date of delivery (EDD), as determined by ultrasound (U/S) and the last menstrual period (LMP).
Number of Pregnancies   [1] 
Mean (Standard Deviation)
Unit of measure:  Pregnancies
Number Analyzed 65 participants 64 participants 129 participants
3.5  (1.9) 4.2  (2.6) 3.8  (2.3)
[1]
Measure Description: Number of pregnancies was reported by the patient in response to a query and confirmed with medical record review when available.
History of Premature Delivery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
11
  16.9%
14
  21.9%
25
  19.4%
History of Ectopic Pregnancy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
2 4 6
History of Miscarriage  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 65 participants 64 participants 129 participants
21
  32.3%
26
  40.6%
47
  36.4%
1.Primary Outcome
Title Number of Participants With Cessation Success at Week 10 After Target Quit Date
Hide Description Participants will be considered to be abstinent if they self-report abstinence (not even a puff of a cigarette) for >7 days prior to the assessment after 10 weeks of treatment post-To Quit Day and have a CO <8 ppm at that time. As per convention, participants are assumed to be smoking if they self-report to be smoking at the time point, cannot be reached to provide data at the time point, fail to provide a breath sample at the time point, or provide a breath sample at the time point that has a CO concentration >8 ppm.
Time Frame 10 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
We tested treatment group differences as a binary abstinence outcome using a repeated measure generalized estimating equations (GEE) model with a logit link. Point prevalence quit rates at the end of week 10 of treatment post-TQD were the primary outcome variables.
Arm/Group Title Placebo Group Bupropion Group
Hide Arm/Group Description:
10 mg placebo daily 10 weeks
10 mg buproprion 10 weeks
Overall Number of Participants Analyzed 65 64
Measure Type: Number
Unit of Measure: Participants with cessation success
12 7
2.Primary Outcome
Title Number Moderate or Severe Side Effects
Hide Description For adverse effects, our primary outcome will be the frequency of moderate or severe side effects from a checklist of bupropion-related side effects (derived from completed bupropion studies), as well as those elicited with open-ended questions, through regular obstetrics visits, and assessments triggered by any pregnancy-related complication. Adverse effects will be systematically assessed by study personnel at 5 time points over the course of the 10-week study and can trigger dose reductions or suspension of medication.
Time Frame 10 week treatment phase
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Bupropion
Hide Arm/Group Description:
Placebo BID, PO for 10 weeks.
Bupropion 150 mg BID, PO for 10 weeks
Overall Number of Participants Analyzed 65 64
Mean (Standard Deviation)
Unit of Measure: adverse effects
.7  (1.2) 1.1  (1.8)
3.Primary Outcome
Title Birth Outcomes for Gestational Age
Hide Description Birth outcomes obtained from labor and delivery records gestational age, measured in weeks.
Time Frame Postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description:
Bupropion 150 mg BID, PO for 10 weeks
Placebo BID, PO for 10 weeks.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: weeks
37.1  (4.7) 38.1  (1.7)
4.Primary Outcome
Title Birth Weight Outcomes
Hide Description Birth weight outcomes were obtained from labor and delivery clinical records. Birth weight is measure in grams.
Time Frame Postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description:
Bupropion 150 mg BID, PO for 10 weeks
Placebo BID, PO for 10 weeks.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: grams
2925.9  (680.5) 2996.5  (521.7)
5.Primary Outcome
Title Birth Outcomes, Size (Percentile) for Gestational Age.
Hide Description Birth outcomes obtained from labor and delivery records infant size for gestational age, whether small for gestational age (i.e., <10th percentile birth weight for gestational age as determined by the Alexander curve).
Time Frame Postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description:
Bupropion 150 mg BID, PO for 10 weeks
Placebo BID, PO for 10 weeks.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: percentile
32.0  (28.2) 32.5  (28.2)
6.Primary Outcome
Title Birth Outcomes Head Circumference.
Hide Description Birth outcomes obtained from labor and delivery records head circumference measured in centimeters.
Time Frame Postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description:
Bupropion 150 mg BID, PO for 10 weeks
Placebo BID, PO for 10 weeks.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: cm
33.3  (1.7) 33.0  (1.8)
7.Primary Outcome
Title Birth Outcomes 5-minute Appearance, Pulse, Grimace, Activity, and Respiration Score
Hide Description Birth outcomes obtained from labor and delivery records 5-minute Appearance, Pulse, Grimace, Activity, and Respiration score (APGAR). The Apgar score has a range from 0 to 10. A 5-minute Apgar score of 7-10 as reassuring, a score of 4-6 as moderately abnormal, and a score of 0-3 as low in the term infant and late-preterm infant 6.
Time Frame postpartum
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Bupropion Placebo
Hide Arm/Group Description:
Bupropion 150 mg BID, PO for 10 weeks
Placebo BID, PO for 10 weeks.
Overall Number of Participants Analyzed 64 65
Mean (Standard Deviation)
Unit of Measure: score on a scale
8.9  (0.3) 8.6  (1.5)
Time Frame Adverse event data were collected from the time subjects received their first dose of study medication until the end of the 10-week treatment period or, if the adverse event was present at 10 weeks, until it resolved, up to 20 weeks.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Bupropion
Hide Arm/Group Description Placebo BID, PO for 10 weeks. Bupropion 150 mg BID, PO for 10 weeks
All-Cause Mortality
Placebo Bupropion
Affected / at Risk (%) Affected / at Risk (%)
Total   0/65 (0.00%)      0/64 (0.00%)    
Hide Serious Adverse Events
Placebo Bupropion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/65 (4.62%)      2/64 (3.13%)    
Pregnancy, puerperium and perinatal conditions     
Spontaneous delivery with Hospitalization   1/65 (1.54%)  1 0/64 (0.00%)  0
Vasa previa   0/65 (0.00%)  0 1/64 (1.56%)  1
Stillbirth with Nuchal Cord   1/65 (1.54%)  1 0/64 (0.00%)  0
Still birth   1/65 (1.54%)  1 1/64 (1.56%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Bupropion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/65 (61.54%)      41/64 (64.06%)    
Gastrointestinal disorders     
Headache *  10/65 (15.38%)  13 13/64 (20.31%)  16
Dry Mouth *  7/65 (10.77%)  7 6/64 (9.38%)  10
Irritability *  6/65 (9.23%)  7 7/64 (10.94%)  11
Sleep problem *  9/65 (13.85%)  9 16/64 (25.00%)  18
Fatigue *  4/65 (6.15%)  4 4/64 (6.25%)  4
Insomnia *  3/65 (4.62%)  3 9/64 (14.06%)  9
Diarrhea *  2/65 (3.08%)  2 5/64 (7.81%)  5
General disorders     
Nausea *  12/65 (18.46%)  15 11/64 (17.19%)  13
Vomiting *  9/65 (13.85%)  11 6/64 (9.38%)  7
Constipation *  8/65 (12.31%)  8 6/64 (9.38%)  7
Depressed Mood *  3/65 (4.62%)  3 4/64 (6.25%)  4
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Henry R. Kranzler, M.D.
Organization: University of Pennsylvania Perelman School of Medicine
Phone: 215-386-6662
EMail: kranzler@pennmedicine.upenn.edu
Layout table for additonal information
Responsible Party: Henry Kranzler, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02188459    
Other Study ID Numbers: 820364
First Submitted: July 9, 2014
First Posted: July 11, 2014
Results First Submitted: January 15, 2021
Results First Posted: May 4, 2021
Last Update Posted: May 4, 2021