Combination Therapy With Varenicline and Bupropion for Smoking Cessation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 506
- 试验地点
- 3
- 主要终点
- Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers.
研究概览
简要总结
This study provides an opportunity to combine varenicline and bupropion SR and capitalize on the potential additive benefit. The investigators hypothesize that this will further increase long-term (≥ 6 months) smoking abstinence rates.
详细描述
Cigarette smoking is the single most important preventable cause of morbidity, mortality and excess health care costs in the United States and accounts for 30% of U.S. cancer deaths. Varenicline and bupropion SR (sustained-release) are non nicotine pharmacotherapies FDA-indicated for the treatment of tobacco dependence in cigarette smokers. Although varenicline has proven greater efficacy than bupropion SR, both medications are associated with high end-of-treatment smoking abstinence rates. However, almost two-thirds of smokers treated with varenicline report smoking at 6 months. Because varenicline and bupropion SR have different mechanisms of action and different neuropharmacologic targets, combination pharmacotherapy with these agents may increase long-term smoking abstinence rates above what is observed with single-agent therapy. In our recent pilot study of combination therapy with varenicline and bupropion SR, we observed treatment to be well-tolerated with 7-day point prevalence smoking abstinence rates of 71% (95% CI: 54-85%) at 3 months and 58% (95% CI: 41-74%) at 6 months. Determining the efficacy of combination therapy compared to single-agent therapy has immediate and important clinical implications. In this study, we will conduct a randomized, multicenter, controlled clinical trial evaluating the efficacy of combination therapy with varenicline and bupropion SR compared to varenicline and placebo in 506 cigarette smokers at the Mayo Clinic in Rochester, MN, and the University of Minnesota in Minneapolis, MN.
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
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is at least 18 years of age;
- •Subject has provide written informed consent;
- •Subject is smoking greater than or equal to 10 cigarettes per day for at least 6 months;
- •Subject is able to complete all study visits 4) Subject is in good health as determined by the investigator 5) Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments 6) Subject is motivated to stop smoking.
排除标准
- •Female and were pregnant, lactating or likely to become pregnant during the trial and not able nor willing to use contraception or had:
- •an unstable medical condition;
- •another household member participating in the study;
- •bupropion or varenicline allergy;
- •current use (previous 30 days) of a tobacco dependence treatment and unable or unwilling to discontinue use;
- •an unstable medical condition or unstable angina, myocardial infarction, or coronary angioplasty (past 3 months) or an untreated cardiac dysrhythmia;
- •a history of renal failure or were on renal dialysis;
- •a history of seizures;
- •as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale), current non-specific suicidal thoughts or lifetime history of a suicidal attempt (defined as "potentially self-injurious act committed with at least some wish to die, as a result of act");
- •a history of closed head trauma associated with > 30 minutes of loss of consciousness, amnesia, skull fracture, subdural hematoma, or brain contusion;
- •a history or psychosis, bipolar disorder, bulimia or anorexia nervosa;
- •current moderate or severe depression as assessed by a score of ≥ 20 on the Beck Depression Inventory, Second Edition (BDI-II) 10;
- •active substance abuse other than nicotine;
- •current (past 14 days) use of an antipsychotic, monoamine oxidase inhibitors, or drugs known to interact with bupropion SR;
- •a recent dose change of their antidepressant (within last 3 months);
- •untreated hypertension or baseline systolic blood pressure > 180 or diastolic > 100;
- •current treatment with another investigational drug for tobacco dependence (previous 30 days); or
- •current use of bupropion or varenicline (previous 30 days).
研究组 & 干预措施
varenicline and buproprion SR
Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.
干预措施: Varenicline (Drug)
varenicline and buproprion SR
Everyone randomized to this arm will receive varenicline (up to 1mg bid) and bupropion SR (150 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.
干预措施: bupropion SR (Drug)
varenicline and placebo
Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.
干预措施: Varenicline (Drug)
varenicline and placebo
Everyone randomized to this arm will receive varenicline (up to 1mg bid) and placebo (0 mg bid)for 12 weeks. They will be followed up by study for an additional 9 months post end of medication - for a total of 1 year study participation. Everyone will receive behavioral counseling for the full year.
干预措施: placebo (Drug)
结局指标
主要结局
Prolonged Smoking Abstinence Rates at 12 Weeks in Cigarettes Smokers.
时间窗: 3 months
Prolonged smoking abstinence is defined as no smoking, not even a puff, in the last 7 days, and a negative response to the question "Since 2 weeks after your target quit date, have you smoked any tobacco, even a puff, for 7 consecutive days or at least once each week on 2 consecutive weeks?"
Point Prevalence Abstinence at 3 Months.
时间窗: 3 months
biochemically confirmed 7-day point prevalence abstinence defined as no smoking, not even a puff, in the previous 7 days.
次要结局
- Prolonged Smoking Abstinence Rates at 26 Weeks in Cigarettes Smokers.(6 months)
- Weight Gain From Baseline to 3 Months(3 months)
- Point Prevalence Abstinence at 6 Months.(6 months)
- Prolonged Abstinence at 12 Months(12 months)
- Point Prevalence Abstinence at 12 Months(12 months)