Extended (6-Week) Varenicline Preloading: Does it Facilitate Smoking Reduction and Cessation?

SUMMARY Rationale: Worldwide, cigarette smoking carries a high mortality. Since the available cessation programs are not effective for all smokers, new strategies are necessary for tobacco control. Primary objective: To investigate whether a 6-week varenicline preloading facilitates smoking reduction and cessation compared with the standard varenicline treatment schedule. Design: Parallel group, double-blind, randomised controlled clinical trial. Participants: Smokers of both sexes from the general population. Methods: Participants will be randomized into two groups of treatment. Subjects in Group A will receive varenicline for six weeks while those in group B will receive placebo for 5 weeks and varenicline for 1 week. During this phase, subjects in both groups will be asked to reduce cigarette smoking by 50 percent. At week 6 all participants will be instructed to stop smoking before receiving 12 weeks of varenicline treatment. Visits will be arranged at randomization, week 4, week 6 (Quit day (QD)) and at week 1, 6, 12, and 24 after QD. Measurements: These will include vital signs, smoking history, spirometry, expired CO, salivary cotinine, nicotine dependence, and withdrawal symptoms. Primary outcome is continuous abstinence at 6 months. Sample size: For an estimated difference of quit rates of 15% at 24 weeks (30% for group A vs. 15% for group B) 121 subjects per group are needed (Total = 242 subjects). Statistical analysis: T tests (rational variables) and x2 test or Fisher's exact test (nominal variables) will be used as appropriate. Expected benefits: This study might contribute to optimize the current use of varenicline.