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.
1. at least 18 years of age;
2. smoking greater than or equal to 10 cigarettes per day for at least 6 months;
3. motivated to stop smoking.
1. an unstable medical condition;
2. unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia;
3. a personal history of seizures;
4. a history of closed head trauma with any loss of consciousness or amnesia in the last 5 years;
5. a history of closed head trauma with greater than or equal to 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion;
6. a history or psychosis, bipolar disorder, bulimia or anorexia nervosa);
7. current depression as assessed by Center for Epidemiologic Studies Depression (CES-D);
8. active substance abuse other than nicotine;
9. used an investigational drug within the last 30 days;
10. current use of using a behavioral or pharmacologic tobacco treatment and unwilling or unable to discontinue use;
11. current use of bupropion or varenicline in the previous 30 days;
12. current (past 14 days) use of antipsychotic or antidepressant;
13. an allergy to bupropion or varenicline;
14. untreated hypertension or baseline systolic blood pressure greater than or equal to 180 or diastolic greater than or equal to 100;
15. another member of their household already participating in this study.
16. All female subjects of childbearing potential who have a positive pregnancy test or refuse to use contraception during participation in the study.
This study includes a screening period in which you will be informed of the study; if you decide to participate you will be asked to sign this study informed consent form. Afterwards you will be asked to undergo a series of screening tests to see if you are eligible to participate in this study. The tests will include questions concerning your medical and smoking history, a brief physical exam, diagnostic tests to determine your nicotine dependence, as well as a pregnancy test using a urine sample. After that you will be randomized (as in the flip of a coin) to one of two groups: vareincline (1 mg by mouth twice a day) AND bupropion (150 mg by mouth twice a day) OR varenicline (1-mg by mouth twice a day) and bupropion placebo (inactive drug) twice a day. You will stay on your assigned dose for 12 weeks with biweekly clinic visits (phone call at week 1 and clinic visits at weeks 2, 4, 6, 8, 10 and 12).
When you complete your 12 weeks of study drug; you will be called at week 13, returnfor a clinic visit at week 14, be called for a visit at week 16 and return for visit at week 26 and then for a final study visit (week 52).
Everyone in study will also receive nicotine dependence counseling.
Last updated: 04/16/2013