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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02188459
Recruitment Status : Completed
First Posted : July 11, 2014
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Henry Kranzler, University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE July 9, 2014
First Posted Date  ICMJE July 11, 2014
Last Update Posted Date February 17, 2020
Actual Study Start Date  ICMJE October 30, 2014
Actual Primary Completion Date January 22, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2015)
  • Number of cigarettes smoked by medication group over 10 week treatment phase. [ Time Frame: 10 Week study period ]
    Number of cigarettes smoked for each participant during the study period. 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 and at 24 weeks post-To Quit Day and have a CO <10 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 >10 ppm.
  • Frequency of moderate or severe side effects. [ Time Frame: 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.
  • Birth outcomes obtained from clinical records. [ Time Frame: Postpartum ]
    Birth outcomes obtained from labor and delivery records (permission for which will be included in the informed consent form) will include gestational age, overall and spontaneous preterm birth (i.e., at less than 37 weeks), infant birth weight, whether small for gestational age (i.e., <10th percentile birth weight for gestational age as determined by the Alexander curve), head circumference, Apgar scores, and NICU admissions. Obstetric complications will include type of delivery and delivery and postpartum complications.
Original Primary Outcome Measures  ICMJE
 (submitted: July 10, 2014)
  • Number of cigarettes smoked by medication group over 10 week treatment phase. [ Time Frame: 10 Week study period ]
    Number of cigarettes smoked for each participant during the study period. 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 and at 24 weeks post-TQD and have a CO <10 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 >10 ppm.
  • Frequency of moderate or severe side effects. [ Time Frame: 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.
  • Birth outcomes obtained from clinical records. [ Time Frame: Postpartum ]
    Birth outcomes obtained from labor and delivery records (permission for which will be included in the informed consent form) will include gestational age, overall and spontaneous preterm birth (i.e., at less than 37 weeks), infant birth weight, whether small for gestational age (i.e., <10th percentile birth weight for gestational age as determined by the Alexander curve), head circumference, Apgar scores, and NICU admissions. Obstetric complications will include type of delivery and delivery and postpartum complications.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 10, 2014)
Smoking frequency after 10 weeks treatment phase. [ Time Frame: Post treatment days to 24 weeks post quit date ]
Secondary smoking cessation outcomes include: smoking rate after 10 weeks of treatment and at 24 weeks post-TQD for non-abstainers, prolonged abstinence to weeks 10 and 24 (defined below), continuous abstinence at weeks 10 and 24 (defined below), time to 7-day relapse (no grace period), and lapse and recovery events.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 10, 2014)
Safety Endpoint [ Time Frame: 10 week treatment phase ]
Participants with severe psychological symptoms (e.g., suicidal thoughts), experiencing a serious adverse event that the Principal Investigator believes to be related to study drug and a potential threat to the health and safety of the participant or fetus will be withdrawn from the study.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women
Official Title  ICMJE Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women
Brief Summary

Smoking during pregnancy adversely affects the health of the mother and her developing baby. Maternal smoking approximately doubles the risk of miscarriage, placental complications, preterm delivery, low birth weight and fetal and newborn death. The most common adverse effect of smoking during pregnancy is low birth weight, which sharply increases the risk of the newborn becoming ill or dying. In the US, maternal smoking is responsible for 30% of low birth weight babies, 10% of premature deliveries, and 5% of infant deaths. Fortunately, smoking cessation by pregnancy week 16, or as late as the third trimester, results in a near-normal weight infant at birth. Even reductions in smoking increase birth weight.

Despite the known risks, the majority of women who are smoking at the time of their first prenatal visit continue to smoke. Bupropion is approved by the US Food and Drug Administration (FDA) for smoking cessation in people who are not pregnant, but there are no carefully controlled studies on the use of Bupropion to help pregnant women quit smoking. Bupropion is also FDA approved to treat depression, and some pregnant women have taken it for that purpose, even though it has not been formally tested. The investigators propose to conduct a randomized, parallel-group, double-blinded, placebo-controlled, 10 week trial of Bupropion in 360 pregnant women who smoke daily and wish to quit smoking.

The study has three primary hypotheses. First, the investigators hypothesize that Bupropion treated subjects will decrease the frequency of smoking more than placebo-treated subjects. Second the investigators hypothesize that Bupropion treated subjects will have greater positive pregnancy and child health outcomes than placebo-treated subjects. Third the investigators hypothesize that Bupropion treated subjects will have decreased frequency of depressive symptoms and cigarette craving than placebo-treated subjects. These finding will provide information on the safety and efficacy of bupropion treat for smoking cessation in pregnant women.

Detailed Description

A. General Design: This is a phase II, prospective, placebo-controlled randomized controlled trial of the efficacy and safety of bupropion in combination with behavioral counseling for smoking cessation during pregnancy. Pregnant smokers (N=360) will receive bupropion or placebo treatment for 10 weeks, under strict double-blind conditions, with 3 post-treatment follow-up sessions: 2 and 6 weeks postpartum (with counseling to prevent relapse or encourage a repeat quit attempt) and monitoring of the persistence of treatment effects at 24 weeks post-quit date.

B. Recruitment: We will distribute IRB (Institutional Review Board)-approved brochures and posters to recruit pregnant women who smoke and wish to quit smoking through participation in the trial. At Penn Medicine sites, we will access the hospitals' EPIC computer programs to identify pregnant smokers receiving prenatal care and, working with their obstetrician, invite them to consider study participation. We will conduct a brief screening interview over the phone or in-person at the participant's obstetrics clinic to assess study eligibility criteria. Prospective participants who appear to meet eligibility criteria for the study will be scheduled for an in-person Informed Consent and Screening visit.

C. Screening Visit: Participants will read and sign the informed consent form, after all of their questions have been answered. Participants will then be asked to provide the researchers with information to determine whether they are eligible to participate in the study. On this visit, participants will be interviewed for about an hour. This interview will include questions about medical and pregnancy history, and any mood or other symptoms and determine the baby's date of delivery. We will also ask about any past or current use of alcohol, drugs, and cigarettes.

D: Baseline Visit: This in-person visit will be completed within 30 days of the screening visit and will last approximately 90 minutes. At the visit, we will measure heart rate and complete questionnaires by telephone and in person. We will take a blood sample (3 tubes, enough to fill 1.5 tablespoons) to be used to conduct genetic testing and to measure the body's ability to break down nicotine, which is contained in cigarettes.

At this visit participants will receive the first of six counseling sessions in the study. This first, "pre-quit" counseling session will last 30 minutes and will help to prepare them to quit smoking. They will be given study medication at this visit and will be instructed to begin taking it the following morning. They will be asked to identify a quit date within a week of beginning the study medication. They will start the study medication by taking one capsule (150 mg/day or placebo, a harmless, inactive substance) each morning for the first 3 days and then one capsule each morning and each evening (150 mg twice daily) for the remainder of the 10-week study treatment period. At this visit, and at every visit while taking the study medication, we will record any side effects that may have been experienced from the study medication. We will also ask participants to return all study medication that they have not taken and the study medication bottle.

The day after the Baseline Visit, the participants will begin to receive two daily text messages. The first message of the day (in the morning) will provide information on the expected development based on the baby's age, accompanied by a reminder to take the study medication. The second message of the day (in the evening) will ask the participants whether they took all of their study medication that day. They'll be asked to text back indicating that they received the message (in the morning) and whether they took the medication that day (in the evening). We will ask them which times they would like to receive the text messages each day. Although the information that they provide will help us to keep track of their participation, the inbox for our texting center is not monitored, so we will direct them to call our study staff to speak with them directly, rather than texting them if they have any study-related questions.

Visit C: Quit Date Visit: The scheduled quit date visit will occur approximately one week after the baseline visit and will last approximately 45 minutes. During this visit, we will measure the participants' heart rate and ask them to blow into an instrument that measures a chemical (carbon monoxide) that is in tobacco smoke. The study nurse will collect any medication not taken and the study medication bottle. The participants will receive a four-week supply of study medication and a study nurse will ask them about any study medication side effects that they may have experienced since starting the study. They will also be asked to complete some questionnaires and will receive 20 minutes of "quit-day" counseling, which will help them to identify things that could cause them to return to smoking and to develop a plan to avoid tempting situations.

Visit D: Week 3: This visit will occur by telephone and will last approximately 25 minutes, during which time the participants will be asked to complete questionnaires over the telephone. They will be asked about their cigarette use since the last visit and any medication side effects they may have experienced. They will also receive 10 minutes of counseling by phone to help them avoid smoking or, if they need to, set another quit date to try again to quit smoking.

Visit E: Week 5: This in-person visit will last approximately 30 minutes. The participants will be asked to complete some questionnaires and be interviewed about their cigarette use since the last visit. We will measure their heart rate and they will be asked to blow into an instrument that measures a chemical (carbon monoxide) that is in tobacco smoke. They will be asked to provide a blood sample (2 tubes, enough to fill 1 tablespoon) to be used to measure the concentration of study medication in the blood. The study nurse will collect any medication that the participants have left as well as the study medication bottle. They will receive a five-week supply of study medication and a study nurse will ask them about any study medication side effects that they may have experienced since starting the study. They will also receive 10 minutes of counseling to help they avoid smoking or, if needed, set another quit date to try quitting again.

Visit F: Week 7: This telephone visit will last approximately 15 minutes. The participants will be asked to complete some questionnaires. They will also be asked about their cigarette use since the last visit and any medication side effects they may have experienced.

Visit G: Endpoint visit: This in-person visit will last approximately 25 minutes. The participants will be asked to complete questionnaires and about their cigarette use since the last visit. During the visit we will measure their heart rate and they will be asked to blow into an instrument that measures a chemical (carbon monoxide) that is in tobacco smoke. The study nurse will collect any medication that they had not taken and the study medication bottle. The study nurse will ask them about any study medication side effects that they may have experienced since starting the study.

Visit H: Week 24 after the Quit Date: About six months after the participants started treatment, they will be contacted by telephone. During this phone call, a research technician will complete several questionnaires with them, similar to those they completed previously. Some participants will be asked to come back to the center following this interview to provide carbon monoxide breath samples as they did previously. Approximately two weeks prior to the phone call we may send a reminder letter that the phone visit is coming up.

Visits I and J: 2 and 6 weeks after delivery: The last two sessions will be held by telephone after the birth of the baby. The participants will be asked to complete several questionnaires, similar to those completed previously. They will also receive 10 minutes of counseling over the phone.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Smoking
  • Nicotine Dependence
Intervention  ICMJE Drug: 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.
Other Name: Wellbutrin
Study Arms  ICMJE
  • Active Comparator: Bupropion
    Bupropion 150 mg BID, PO for 10 weeks
    Intervention: Drug: Bupropion
  • Placebo Comparator: Placebo
    Placebo BID, PO for 10 weeks. The formulation appears identical to the bupropion capsules.
    Intervention: Drug: Bupropion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 13, 2020)
129
Original Estimated Enrollment  ICMJE
 (submitted: July 10, 2014)
360
Actual Study Completion Date  ICMJE January 22, 2020
Actual Primary Completion Date January 22, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Currently smoking on average 3 or more cigarettes per day for the preceding 7 days with a breath CO of at least 5 ppm and wants to quit smoking
  2. Pregnant at 13-26 weeks gestation (to maximize safety and the likelihood of receiving 10 weeks of treatment)
  3. >18 years of age
  4. Able to speak and read English at a 6th grade level or higher, using the Slosson Oral Reading Test (SORT)
  5. Committed to remaining in the geographic area for at least 3 months postpartum
  6. Able to sign written informed consent and commit to completing the procedures involved in the study.
  7. Methadone or buprenorphine-maintained women must be in methadone or buprenorphine treatment for a minimum of 2 weeks prior to entering the study. Their 2 most recent urine drug screens, consecutive and administered at least one week apart, must both be positive for methadone or buprenorphine and negative for drugs of abuse other than cannabis. Participants who screen positive for other drugs at either time point will not be enrolled in the study until they meet this criterion.

Exclusion Criteria:

  1. During the last 90 days from screening visit, meets any criteria for a DSM-IV diagnosis of drug or alcohol dependence—excluding tobacco or cannabis dependence and, for methadone or buprenorphine maintenance patients, opioid dependence—AND either evidences ongoing use of illicit drugs other than cannabis or continues to abuse or misuse prescription drugs such as CNS stimulants.
  2. Pregnant with triplets or higher order multiple gestations
  3. Has an unstable psychiatric disorder (i.e., suicide risk moderate or severe, as reflected by a score of >9 on the MINI Section B (Suicidality) or a suicide attempt during the preceding year, psychiatric hospitalization within the last 3 months; current psychotic disorder based on the MINI)
  4. Current or past Bipolar Disorder as determined by a study psychiatrist or psychologist based on assessment with the MINI, relevant information from the medical record and, when warranted, direct clinical evaluation.
  5. Current, regular use of psychotropic medication, inhibitors of CYP2B6 (e.g., ticlopidine, clopidogrel), inducers of CYP2B6 (e.g., ritonavir, lopinavir, efavirenz), anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin), beta-blockers (e.g., metoprolol), Type 1C antiarrhythmics (e.g., propafenone and flecainide), drugs that require metabolic activation by CYP2D6 to be effective (e.g., tamoxifen), drugs that lower seizure threshold (e.g., antipsychotics, tricyclic antidepressants, theophylline, or systemic corticosteroids), levodopa or amantadine
  6. Current unstable medical problems or potential inability to tolerate study treatment [e.g., threatened abortion: current persistent hyperemesis gravidarum (HEG) requiring intravenous fluids (to be rescreened when HEG is stabilized/resolved and no electrolyte abnormalities are evident); hypertension with evidence of end organ dysfunction or on more than 2 medications at the start of the pregnancy]; arteriovenous malformation; AIDS; laboratory evidence of hepatic impairment (e.g. viral hepatitis with serum transaminase levels more than twice the upper limit of normal) ; renal impairment (e.g., elevated creatinine or creatinine clearance <75cc/hr), metabolic disorders (e.g., hypoglycemia, hyponatremia) or end organ damage from any chronic medical condition (e.g. abnormal pulmonary function tests), glaucoma, or other significant medical problems that in the opinion of a study obstetrician makes the risk of study participation unacceptable.
  7. Known major fetal congenital malformation—as determined by the study obstetrician—diagnosed prior to study randomization
  8. History of seizure disorder
  9. Current use of a smoking cessation medication in addition to the study medication, such as nicotine replacement therapy
  10. Current or history of bulimia or anorexia nervosa
  11. Current use of tobacco products other than cigarettes (e.g., E-cigarettes)
  12. Current clinically significantly abnormal laboratory evaluations that are not adequately controlled by standard of care treatment.
  13. History of severe head injury (i.e., with loss of consciousness)
  14. Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
  15. Inability to provide informed consent or judged by the Principal Investigator and/or Study Physician to be an unsuitable candidate for a clinical drug trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02188459
Other Study ID Numbers  ICMJE 820364
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Henry Kranzler, University of Pennsylvania
Study Sponsor  ICMJE Henry Kranzler
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Henry R Kranzler, M.D. University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP