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

NCT02188459 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 820364
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 3

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.

Conditions

Smoking; Nicotine Dependence

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Cessation Success at Week 10 After Target Quit Date

  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.

  10 weeks

• Number Moderate or Severe Side Effects

  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.

  10 week treatment phase

• Birth Outcomes for Gestational Age

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

  Postpartum

• Birth Weight Outcomes

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

  Postpartum

• Birth Outcomes, Size (Percentile) for Gestational Age.

  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).

  Postpartum

• Birth Outcomes Head Circumference.

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

  Postpartum

• Birth Outcomes 5-minute Appearance, Pulse, Grimace, Activity, and Respiration Score

  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.

  postpartum

Study Arms (2)

Bupropion

ACTIVE COMPARATOR

Bupropion 150 mg BID, PO for 10 weeks

Drug: Bupropion

Placebo

PLACEBO COMPARATOR

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

Drug: Bupropion

Interventions

Bupropion DRUG

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.

Also known as: Wellbutrin

Bupropion; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Pregnant at 13-26 weeks gestation (to maximize safety and the likelihood of receiving 10 weeks of treatment)
• \>18 years of age
• Able to speak and read English at a 6th grade level or higher, using the Slosson Oral Reading Test (SORT)
• Committed to remaining in the geographic area for at least 3 months postpartum
• Able to sign written informed consent and commit to completing the procedures involved in the study.
• 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.

You may not qualify if:

• 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.
• Pregnant with triplets or higher order multiple gestations
• 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)
• 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.
• 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
• 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.
• Known major fetal congenital malformation-as determined by the study obstetrician-diagnosed prior to study randomization
• History of seizure disorder
• Current use of a smoking cessation medication in addition to the study medication, such as nicotine replacement therapy
• Current or history of bulimia or anorexia nervosa
• Current use of tobacco products other than cigarettes (e.g., E-cigarettes)
• Current clinically significantly abnormal laboratory evaluations that are not adequately controlled by standard of care treatment.
• History of severe head injury (i.e., with loss of consciousness)
• Any medical condition or concomitant medication that could compromise subject safety or treatment, as determined by the Principal Investigator and/or Study Physician.
• 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.

Sponsors & Collaborators

• Henry Kranzler: lead

Study Sites (3)

Christiana Care Health System

Newark, Delaware, 19713, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Kranzler HR, Washio Y, Zindel LR, Wileyto EP, Srinivas S, Hand DJ, Hoffman M, Oncken C, Schnoll RA. Placebo-controlled trial of bupropion for smoking cessation in pregnant women. Am J Obstet Gynecol MFM. 2021 Nov;3(6):100315. doi: 10.1016/j.ajogmf.2021.100315. Epub 2021 Jan 22.

  PMID: 33493703 DERIVED

MeSH Terms

Conditions

Smoking; Tobacco Use Disorder

Interventions

Bupropion

Condition Hierarchy (Ancestors)

Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Results Point of Contact

• Title: Henry R. Kranzler, M.D.
• Organization: University of Pennsylvania Perelman School of Medicine

kranzler@pennmedicine.upenn.edu

215-386-6662

Study Officials

• Henry R Kranzler, M.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: July 9, 2014
• First Posted: July 11, 2014
• Study Start: October 30, 2014
• Primary Completion: January 22, 2020
• Study Completion: January 22, 2020
• Last Updated: May 4, 2021
• Results First Posted: May 4, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)