Trial Outcomes & Findings for Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women (NCT NCT02188459)

Last Updated: 2021-05-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

129 participants

Primary outcome timeframe

10 weeks

Results posted on

2021-05-04

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Bupropion 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 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.
Overall Study STARTED	64	65
Overall Study COMPLETED	61	58
Overall Study NOT COMPLETED	3	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Bupropion 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 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.
Overall Study Lost to Follow-up	3	4
Overall Study Early Termination	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=65 Participants Placebo BID, PO for 10 weeks.	Bupropion n=64 Participants Bupropion 150 mg BID, PO for 10 weeks	Total n=129 Participants Total of all reporting groups
Age, Continuous	28.1 years STANDARD_DEVIATION 4.7 • n=99 Participants	29.0 years STANDARD_DEVIATION 5.0 • n=107 Participants	28.5 years STANDARD_DEVIATION 4.8 • n=206 Participants
Sex/Gender, Customized Female	65 Participants n=99 Participants	64 Participants n=107 Participants	129 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	35 Participants n=99 Participants	32 Participants n=107 Participants	67 Participants n=206 Participants
Race (NIH/OMB) White	30 Participants n=99 Participants	32 Participants n=107 Participants	62 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	65 Participants n=99 Participants	64 Participants n=107 Participants	129 Participants n=206 Participants
Education (% High School Graduate or less)	21 Participants n=99 Participants	18 Participants n=107 Participants	39 Participants n=206 Participants
Annual Household Income (<40K)	49 Participants n=99 Participants	47 Participants n=107 Participants	96 Participants n=206 Participants
Marital Status (% Partnered)	25 Participants n=99 Participants	22 Participants n=107 Participants	47 Participants n=206 Participants
Depression (PHQ-9)	4.9 Total score STANDARD_DEVIATION 3.8 • n=99 Participants	5.4 Total score STANDARD_DEVIATION 4.1 • n=107 Participants	5.1 Total score STANDARD_DEVIATION 3.9 • n=206 Participants
Fagerstrom Test for Nicotine Dependence	3.8 Total score STANDARD_DEVIATION 1.9 • n=99 Participants	3.8 Total score STANDARD_DEVIATION 1.9 • n=107 Participants	3.8 Total score STANDARD_DEVIATION 1.9 • n=206 Participants
Cigarettes/Day in Past 30 Days	7.9 Cigarettes per day STANDARD_DEVIATION 4.5 • n=99 Participants	8.0 Cigarettes per day STANDARD_DEVIATION 4.2 • n=107 Participants	7.9 Cigarettes per day STANDARD_DEVIATION 4.3 • n=206 Participants
Breath CO, ppm	8.3 parts per million STANDARD_DEVIATION 5.2 • n=99 Participants	9.2 parts per million STANDARD_DEVIATION 5.7 • n=107 Participants	8.8 parts per million STANDARD_DEVIATION 5.4 • n=206 Participants
Total number of years smoking cigarettes	12.0 Totals years smoking cigarettes STANDARD_DEVIATION 5.5 • n=99 Participants	13.0 Totals years smoking cigarettes STANDARD_DEVIATION 5.1 • n=107 Participants	12.5 Totals years smoking cigarettes STANDARD_DEVIATION 5.3 • n=206 Participants
Number of Times Quit Smoking for >24 Hours	2.9 number of times quit smoking cigarettes STANDARD_DEVIATION 2.7 • n=99 Participants	3.8 number of times quit smoking cigarettes STANDARD_DEVIATION 7.0 • n=107 Participants	3.3 number of times quit smoking cigarettes STANDARD_DEVIATION 5.3 • n=206 Participants
Weeks of Gestational Age	18.5 Weeks STANDARD_DEVIATION 4.6 • n=99 Participants	18.4 Weeks STANDARD_DEVIATION 4.2 • n=107 Participants	18.4 Weeks STANDARD_DEVIATION 4.4 • n=206 Participants
Number of Pregnancies	3.5 pregnancies STANDARD_DEVIATION 1.9 • n=99 Participants	4.2 pregnancies STANDARD_DEVIATION 2.6 • n=107 Participants	3.8 pregnancies STANDARD_DEVIATION 2.3 • n=206 Participants
History of Premature Delivery	11 Participants n=99 Participants	14 Participants n=107 Participants	25 Participants n=206 Participants
History of Ectopic Pregnancy	2 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants
History of Miscarriage	21 Participants n=99 Participants	26 Participants n=107 Participants	47 Participants n=206 Participants

PRIMARY outcome

Timeframe: 10 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo Group n=65 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=64 Participants 10 mg buproprion 10 weeks
Number of Participants With Cessation Success at Week 10 After Target Quit Date	12 Participants with cessation success	7 Participants with cessation success

PRIMARY outcome

Timeframe: 10 week treatment phase

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.

Outcome measures

Outcome measures
Measure	Placebo Group n=65 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=64 Participants 10 mg buproprion 10 weeks
Number Moderate or Severe Side Effects	.7 adverse effects Standard Deviation 1.2	1.1 adverse effects Standard Deviation 1.8

PRIMARY outcome

Timeframe: Postpartum

Birth outcomes obtained from labor and delivery records gestational age, measured in weeks.

Outcome measures

Outcome measures
Measure	Placebo Group n=64 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=65 Participants 10 mg buproprion 10 weeks
Birth Outcomes for Gestational Age	37.1 weeks Standard Deviation 4.7	38.1 weeks Standard Deviation 1.7

PRIMARY outcome

Timeframe: Postpartum

Birth weight outcomes were obtained from labor and delivery clinical records. Birth weight is measure in grams.

Outcome measures

Outcome measures
Measure	Placebo Group n=64 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=65 Participants 10 mg buproprion 10 weeks
Birth Weight Outcomes	2925.9 grams Standard Deviation 680.5	2996.5 grams Standard Deviation 521.7

PRIMARY outcome

Timeframe: Postpartum

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).

Outcome measures

Outcome measures
Measure	Placebo Group n=64 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=65 Participants 10 mg buproprion 10 weeks
Birth Outcomes, Size (Percentile) for Gestational Age.	32.0 percentile Standard Deviation 28.2	32.5 percentile Standard Deviation 28.2

PRIMARY outcome

Timeframe: Postpartum

Birth outcomes obtained from labor and delivery records head circumference measured in centimeters.

Outcome measures

Outcome measures
Measure	Placebo Group n=64 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=65 Participants 10 mg buproprion 10 weeks
Birth Outcomes Head Circumference.	33.3 cm Standard Deviation 1.7	33.0 cm Standard Deviation 1.8

PRIMARY outcome

Timeframe: postpartum

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.

Outcome measures

Outcome measures
Measure	Placebo Group n=64 Participants 10 mg placebo daily 10 weeks	Bupropion Group n=65 Participants 10 mg buproprion 10 weeks
Birth Outcomes 5-minute Appearance, Pulse, Grimace, Activity, and Respiration Score	8.9 score on a scale Standard Deviation 0.3	8.6 score on a scale Standard Deviation 1.5

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 40 other events

Deaths: 0 deaths

Bupropion

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=65 participants at risk Placebo BID, PO for 10 weeks.	Bupropion n=64 participants at risk Bupropion 150 mg BID, PO for 10 weeks
Pregnancy, puerperium and perinatal conditions Spontaneous delivery with Hospitalization	1.5% 1/65 • Number of events 1 • 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.	0.00% 0/64 • 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.
Pregnancy, puerperium and perinatal conditions Vasa previa	0.00% 0/65 • 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.	1.6% 1/64 • Number of events 1 • 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.
Pregnancy, puerperium and perinatal conditions Stillbirth with Nuchal Cord	1.5% 1/65 • Number of events 1 • 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.	0.00% 0/64 • 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.
Pregnancy, puerperium and perinatal conditions Still birth	1.5% 1/65 • Number of events 1 • 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.	1.6% 1/64 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	Placebo n=65 participants at risk Placebo BID, PO for 10 weeks.	Bupropion n=64 participants at risk Bupropion 150 mg BID, PO for 10 weeks
Gastrointestinal disorders Headache	15.4% 10/65 • Number of events 13 • 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.	20.3% 13/64 • Number of events 16 • 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.
General disorders Vomiting	13.8% 9/65 • Number of events 11 • 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.	9.4% 6/64 • Number of events 7 • 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.
General disorders Constipation	12.3% 8/65 • Number of events 8 • 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.	9.4% 6/64 • Number of events 7 • 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.
Gastrointestinal disorders Dry Mouth	10.8% 7/65 • Number of events 7 • 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.	9.4% 6/64 • Number of events 10 • 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.
Gastrointestinal disorders Irritability	9.2% 6/65 • Number of events 7 • 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.	10.9% 7/64 • Number of events 11 • 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.
Gastrointestinal disorders Sleep problem	13.8% 9/65 • Number of events 9 • 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.	25.0% 16/64 • Number of events 18 • 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.
Gastrointestinal disorders Fatigue	6.2% 4/65 • Number of events 4 • 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.	6.2% 4/64 • Number of events 4 • 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.
General disorders Depressed Mood	4.6% 3/65 • Number of events 3 • 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.	6.2% 4/64 • Number of events 4 • 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.
Gastrointestinal disorders Insomnia	4.6% 3/65 • Number of events 3 • 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.	14.1% 9/64 • Number of events 9 • 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.
Gastrointestinal disorders Diarrhea	3.1% 2/65 • Number of events 2 • 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.	7.8% 5/64 • Number of events 5 • 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.
General disorders Nausea	18.5% 12/65 • Number of events 15 • 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.	17.2% 11/64 • Number of events 13 • 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.

Additional Information

Henry R. Kranzler, M.D.

University of Pennsylvania Perelman School of Medicine

Phone: 215-386-6662

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place