Bupropion for Smoking Cessation During Pregnancy

• Sponsor: The University of Texas Medical Branch, Galveston (Other)
• Overall Status: Completed
• CT.gov ID: NCT01390246
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH), UConn Health (Other)
• Enrollment: 65
• Location: 1
• Arms: 2
• Duration (Months): 65.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This is a prospective, double-blind placebo-controlled randomized pilot trial of the preliminary safety and efficacy of bupropion SR in combination with behavioral counseling for smoking cessation during pregnancy.

Condition or Disease	Intervention/Treatment	Phase
Pregnancy Related; Tobacco Use Disorder	Drug: Bupropion SR; Behavioral: Smoking Cessation Counseling; Drug: Placebo	Phase 4

Detailed Description

This is a prospective, double-blind placebo-controlled randomized pilot trial of the preliminary safety and efficacy of bupropion SR in combination with behavioral counseling for smoking cessation during pregnancy. A total of 150 pregnant smokers will receive medication (75) or placebo (75) for 12 weeks. Compassionate care/continuance of therapy will be available to pregnant subjects. Women who relapse to smoking postpartum will be offered an additional course of medication treatment. All subjects regardless of adherence with 12 week study drug administration period and smoking habits during pregnancy will be followed through the duration of their pregnancy, delivery, and 6-month postpartum period. Subject participation will begin between 13-30 wks of gestation and end 6 months postpartum. Participation will be ten (10) to thirteen(13) months in length.

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Bupropion for Smoking Cessation During Pregnancy
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bupropion SR + cessation counseling Bupropion SR and smoking cessation counseling Subjects received Bupropion SR 150 mg tablet orally twice daily (BID) for 12 weeks. Subjects were instructed to begin using study medication (bupropion SR 150 mg orally for 3 days, then BID for 4 days) on study visit day 1, which was approximately 1 week prior to their quit date. Thereafter, they were continued to dose Bupropion SR 150 mg tablet orally BID for a total medication treatment of 12 full weeks. Smoking cessation counseling included 35-minute counseling sessions at each of the first 2 visits and 10 minutes of smoking cessation counseling at subsequent visits, provided by the trained study nurse.	Drug: Bupropion SR; Bupropion SR 150 mg tablet; Other Names: Zyban buproban ; Behavioral: Smoking Cessation Counseling; 35-min counseling by trained research nurse; Other Names: Behavioral counseling
Placebo Comparator: Placebo + cessation counseling Placebo and smoking cessation counseling Subjects received matching Bupropion SR placebo tablet orally twice daily (BID) for 12 weeks. Subjects were instructed to begin using study medication (matched placebo tablets orally for 3 days, then BID for 4 days) on study visit day 1, which was approximately 1 week prior to their quit date. Thereafter, they were continued to dose matching Bupropion SR placebo tablet orally BID for a total medication treatment of 12 full weeks of therapy. Smoking cessation counseling included 35-minute counseling sessions at each of the first 2 visits and 10 minutes of smoking cessation counseling at subsequent visits, provided by the trained study nurse.	Behavioral: Smoking Cessation Counseling; 35-min counseling by trained research nurse; Other Names: Behavioral counseling ; Drug: Placebo; Matching Bupropion SR placebo tablet; Other Names: Control

Outcome Measures

Primary Outcome Measures

1. Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment [During treatment: Visits 2-6 (time period between 2nd and 12th week of therapy)]

   Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal.

2. Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date [Quit date, visit 2 (one week after starting the 12-week course of therapy)]

   Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal.

3. Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6) [Visit 6 (end of 12 weeks of medication therapy)]

   The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome.

4. Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7) [End of pregnancy (visit 7) is a time period between 36.0-38.6 weeks gestation]

   The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• smoking at least 10 CPD prior to pregnancy and 5 CPD for the preceding 7 days

• 13-30 weeks gestation

• ≥18 years of age

• able to speak English or Spanish

• intent to carry pregnancy to term

• stable residence

Exclusion Criteria:

• current illicit drug or alcohol abuse or dependence

• twins or other multiple gestation

• treatment for psychiatric disorder within the last 6 months

• unstable medical problems (eg, hypertension (BP>140/90), preeclampsia, threatened abortion, hyperemesis gravidarum)

• known congenital abnormality

• seizure disorder

• use of psychotropic medication

• use of medication known to lower the seizure threshold

• anorexia/bulimia

• a personal history of closed head trauma with > 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion

• use of any other smoking cessation treatment in the past 30 days

• current enrollment in methadone treatment program

• prior pregnancy with preeclampsia diagnosis

• chronic hypertension (past history or current diagnosis)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas Medical Branch at Galveston	Galveston	Texas	United States	77555

Sponsors and Collaborators

• The University of Texas Medical Branch, Galveston
• National Institute on Drug Abuse (NIDA)
• UConn Health

Investigators

• Principal Investigator: Gary DV Hankins, MD, University of Texas Medical Branch at Galveston
• Principal Investigator: Tatiana Nanovskaya, PhD, University of Texas Medical Branch at Galveston
• Principal Investigator: Cheryl Onken, MD, MPH, UConn Health
• Principal Investigator: Mahmoud Ahmed, PhD, University of Texas Medical Branch at Galveston
• Principal Investigator: Shannon Clark, MD, University of Texas Medical Branch at Galveston

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: The University of Texas Medical Branch, Galveston
• ClinicalTrials.gov Identifier: NCT01390246
• Other Study ID Numbers: 10-217; R01DA030998
• First Posted: Jul 8, 2011
• Last Update Posted: Jun 7, 2019
• Last Verified: Feb 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by The University of Texas Medical Branch, Galveston: Pregnancy; Tobacco use disorder; Smoking cessation; Bupropion SR; Zyban
• Additional relevant MeSH terms: Tobacco Use Disorder; Bupropion

Study Results

Participant Flow

Recruitment Details	Pregnant smokers were recruited through the UTMB Ob/Gyn Department clinics and Regional Maternal Child Health Program (RMCHP) clinics. The study was also advertised through printed flyers, posters, and electronic media in clinic waiting areas. UTMB OB providers were notified of the study as well to refer potential participants.
Pre-assignment Detail	Psychological screening using the PRIME MD survey was administered after enrollment at the first Study Visit. Using the score, subjects with evidence of major depression or any other severe, acute psychiatric symptom (eg, psychosis) were considered screen failures and referred back to their prenatal provider for treatment.

Arm/Group Title	Bupropion SR	Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
Period Title: Overall Study
STARTED	30	35
Visit 2: Quit Day	24	24
Visit 6: End of Treatment	15	15
Visit 7: 36-38 Weeks Gestation	10	10
COMPLETED	10	10
NOT COMPLETED	20	25

Baseline Characteristics

Arm/Group Title	Bupropion SR	Placebo	Total
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Total of all reporting groups
Overall Participants	30	35	65
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	30 100%	35 100%	65 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.5 (5.56)	27.5 (6.52)	26.2 (6.2)
Sex: Female, Male (Count of Participants)
Female	30 100%	35 100%	65 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 13.3%	5 14.3%	9 13.8%
Not Hispanic or Latino	25 83.3%	30 85.7%	55 84.6%
Unknown or Not Reported	1 3.3%	0 0%	1 1.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 10%	13 37.1%	16 24.6%
White	27 90%	22 62.9%	49 75.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	30 100%	35 100%	65 100%

Outcome Measures

1. Primary Outcome

Title	Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups During Medication Treatment
Description	Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal.
Time Frame	During treatment: Visits 2-6 (time period between 2nd and 12th week of therapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion SR	Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
Measure Participants	24	24
Craving for tobacco	1.50 (1.11)	2.07 (1.23)
Total score of withdrawal excluding craving	3.77 (4.27)	5.35 (5.14)

2. Primary Outcome

Title	Change in Cigarette Craving and Total Nicotine Withdrawal Symptoms Between Groups on the Quit Date
Description	Cigarette craving and withdrawal symptoms were assessed by the Minnesota Nicotine Withdrawal Scale (MNWS). MNWS consists of 7 objectives (e.g., irritability, anxious, depressed mood, difficulty concentrating, increased appetite, insomnia, restless). Subjects were given a score on each item on a scale of 0 (not present) to 4 (severe). Summed (total) score excluding craving represent subject's symptoms of tobacco withdrawal, ranging from 0 to 28. We calculated a craving for tobacco score and a total score of withdrawal symptoms excluding craving. The higher score represent more sever craving and withdrawal.
Time Frame	Quit date, visit 2 (one week after starting the 12-week course of therapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion SR	Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
Measure Participants	24	24
Craving for tobacco	2.04 (1.08)	2.33 (1.31)
Total score of withdrawal excluding craving	4.75 (4.87)	4.88 (4.61)

3. Primary Outcome

Title	Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Medication Treatment (Visit 6)
Description	The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome.
Time Frame	Visit 6 (end of 12 weeks of medication therapy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion SR	Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
Measure Participants	30	35
Count of Participants [Participants]	5 16.7%	1 2.9%

4. Primary Outcome

Title	Number of Participants With 7-day Point Prevalence Smoking Abstinence at the End of Pregnancy (Visit 7)
Description	The accuracy of self-reported smoking abstinence during study visits was confirmed by an exhaled carbon monoxide (CO) levels and by urinary cotinine levels. 7-day point prevalence abstinence was defined as no cigarettes (not even a puff) in the last 7 days, levels of (CO) in exhaled air < 4 ppm, and concentrations of cotinine in urine < 50 ng/mL. At every visit, a research nurse monitored the smoking status of all subjects (amount of cigarettes per day, exhaled CO). Exhaled CO was measured using a Vitalograph carbon monoxide monitor (Lenexa, KS) according to the manufacturer's recommendations. A urine sample was collected at each visit and cotinine in urine was quantified using the validated liquid chromatography-mass spectrometry (LC/MS) method. We calculated the total number of abstinent subjects. The higher the number the better outcome.
Time Frame	End of pregnancy (visit 7) is a time period between 36.0-38.6 weeks gestation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupropion SR	Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.	Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
Measure Participants	30	35
Count of Participants [Participants]	3 10%	1 2.9%

Adverse Events

Time Frame	For each pregnant woman, adverse events were assessed from enrollment through completion (or six months post partum). Neonatal adverse events were assessed at delivery and through infant discharge.
Adverse Event Reporting Description	We monitored for maternal AEs that could be related to bupropion, such as seizures, consistent BP >140/90 mm Hg, headache, insomnia, rhinitis, dry mouth, and anxiety. We defined a priori which AEs would be considered fetal and neonatal SAEs: intrauterine fetal demise, preterm delivery <34 weeks, clinically suspected fetal growth restriction, congenital malformations, cardiovascular anomalies, low birthweight (<10%), Apgar scores <7 at 5 minutes, and neonatal length of hospital stay >3 days.
Arm/Group Title	Bupropion SR		Placebo
Arm/Group Description	Subjects received 150 mg tablet bupropion SR orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.		Subjects received matched bupropion SR placebo tablet orally once daily for three days followed by twice daily for a total medication treatment of 12 weeks. Subjects also received behavioral interventions, which included 35-minute counseling sessions at each of the first 2 visits (enrollment and on the quit day) and 10 minutes of smoking cessation counseling at subsequent visits.
All Cause Mortality
	Bupropion SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/35 (0%)
Serious Adverse Events
	Bupropion SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)		5/35 (14.3%)
Pregnancy, puerperium and perinatal conditions
Infant stay in NICU >3 days due to premature delivery	0/30 (0%)		4/35 (11.4%)
Preeclampsia	1/30 (3.3%)		0/35 (0%)
Cord blood pH <7.01	1/30 (3.3%)		0/35 (0%)
Gestational Diabetes	0/30 (0%)		1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	Bupropion SR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/30 (46.7%)		8/35 (22.9%)
Gastrointestinal disorders
Dry mouth	13/30 (43.3%)		7/35 (20%)
Nervous system disorders
Headache	12/30 (40%)		6/35 (17.1%)
Difficulty sleeping	10/30 (33.3%)		7/35 (20%)
Psychiatric disorders
Anxiety	14/30 (46.7%)		6/35 (17.1%)
Respiratory, thoracic and mediastinal disorders
Rhinorhea- Runny Nose	10/30 (33.3%)		8/35 (22.9%)

Limitations/Caveats

Factors affecting enrollment included social stigma of prenatal smoking and use of medications; high rate of early withdrawal/lost to follow since longitudinal

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.