Methods:

This was a randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in seven centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses. Participants were randomized to either nicotine or placebo patch treatment, which began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13. Tobacco abstinence was confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary endpoint was the 4-week exhaled carbon monoxide–confirmed continuous abstinence rate for weeks 9-12 of treatment, i.e., the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary endpoints included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9-24, and adverse events.