Placebo-controlled Trial of Bupropion for Smoking Cessation in Pregnant Women
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 129
- 试验地点
- 3
- 主要终点
- Birth Weight Outcomes
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Bupropion
Bupropion 150 mg BID, PO for 10 weeks
干预措施: Bupropion (Drug)
Placebo
Placebo BID, PO for 10 weeks. The formulation appears identical to the bupropion capsules.
干预措施: Bupropion (Drug)
结局指标
主要结局
Birth Weight Outcomes
时间窗: Postpartum
Birth weight outcomes were obtained from labor and delivery clinical records. Birth weight is measure in grams.
Number of Participants With Cessation Success at Week 10 After Target Quit Date
时间窗: 10 weeks
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.
Birth Outcomes Head Circumference.
时间窗: Postpartum
Birth outcomes obtained from labor and delivery records head circumference measured in centimeters.
Birth Outcomes 5-minute Appearance, Pulse, Grimace, Activity, and Respiration Score
时间窗: 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.
Number Moderate or Severe Side Effects
时间窗: 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 for Gestational Age
时间窗: Postpartum
Birth outcomes obtained from labor and delivery records gestational age, measured in weeks.
Birth Outcomes, Size (Percentile) for Gestational Age.
时间窗: 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).
次要结局
未报告次要终点
研究者
Henry Kranzler
M.D.
University of Pennsylvania