BACKGROUND: Placebo-controlled trials indicate that cytisine, a partial agonist 
that binds the nicotinic acetylcholine receptor and is used for smoking 
cessation, almost doubles the chances of quitting at 6 months. We investigated 
whether cytisine was at least as effective as nicotine-replacement therapy in 
helping smokers to quit.
METHODS: We conducted a pragmatic, open-label, noninferiority trial in New 
Zealand in which 1310 adult daily smokers who were motivated to quit and called 
the national quitline were randomly assigned in a 1:1 ratio to receive cytisine 
for 25 days or nicotine-replacement therapy for 8 weeks. Cytisine was provided 
by mail, free of charge, and nicotine-replacement therapy was provided through 
vouchers for low-cost patches along with gum or lozenges. Low-intensity, 
telephone-delivered behavioral support was provided to both groups through the 
quitline. The primary outcome was self-reported continuous abstinence at 1 
month.
RESULTS: At 1 month, continuous abstinence from smoking was reported for 40% of 
participants receiving cytisine (264 of 655) and 31% of participants receiving 
nicotine-replacement therapy (203 of 655), for a difference of 9.3 percentage 
points (95% confidence interval, 4.2 to 14.5). The effectiveness of cytisine for 
continuous abstinence was superior to that of nicotine-replacement therapy at 1 
week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary 
outcome, cytisine was superior to nicotine-replacement therapy among women and 
noninferior among men. Self-reported adverse events over 6 months occurred more 
frequently in the cytisine group (288 events among 204 participants) than in the 
group receiving nicotine-replacement therapy (174 events among 134 
participants); adverse events were primarily nausea and vomiting and sleep 
disorders.
CONCLUSIONS: When combined with brief behavioral support, cytisine was found to 
be superior to nicotine-replacement therapy in helping smokers quit smoking, but 
it was associated with a higher frequency of self-reported adverse events. 
(Funded by the Health Research Council of New Zealand; Australian New Zealand 
Clinical Trials Registry number, ACTRN12610000590066.).