BACKGROUND: Smokers need effective support to maximise the chances of successful 
quit attempts. Current smoking cessation medications, such as nicotine 
replacement therapy (NRT), bupropion, nortriptyline or varenicline, have been 
shown to be effective in clinical trials but are underused by smokers attempting 
to quit due to adverse effects, contraindications, low acceptability and/or high 
cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a 
smoking cessation aid in Eastern Europe for 50 years. A systematic review of 
trial evidence suggests that cytisine has a positive impact on both short- and 
long-term abstinence rates compared to placebo. However, the quality of the 
evidence is poor and insufficient for licensing purposes in many Western 
countries. A large, well-conducted placebo-controlled trial (n = 740) of 
cytisine for smoking cessation has recently been published and confirms the 
findings of earlier studies, with 12-month continuous abstinence rates of 8.4% 
in the cytisine group compared to 2.4% in the placebo group (Relative risk = 
3.4, 95% confidence intervals 1.7-7.1). No research has yet been undertaken to 
determine the effectiveness of cytisine relative to that of NRT.
METHODS/DESIGN: A single-blind, randomised controlled, non-inferiority trial has 
been designed to determine whether cytisine is at least as effective as NRT in 
assisting smokers to remain abstinent for at least one month. Participants (n = 
1,310) will be recruited through the national telephone-based Quitline service 
in New Zealand and randomised to receive a standard 25-day course of cytisine 
tablets (Tabex®) or usual care (eight weeks of NRT patch and/or gum or lozenge). 
Participants in both study arms will also receive a behavioural support 
programme comprising an average of three follow-up telephone calls delivered 
over an eight-week period by Quitline. The primary outcome is continuous 
abstinence from smoking at one month, defined as not smoking more than five 
cigarettes since quit date. Outcome data will also be collected at one week, two 
months and six months post-quit date.
DISCUSSION: Cytisine appears to be effective compared with placebo, and given 
its (current) relative low cost may be an acceptable smoking cessation treatment 
for smokers, particularly those in low- and middle-income countries. Cytisine's 
'natural' product status may also increase its acceptability and use among 
certain groups of smokers, such as indigenous people, smokers in countries where 
the use of natural medicines is widespread (e.g. China, India), and in those 
people who do not want to use NRT or anti-depressants to help them quit smoking. 
However it is important to ascertain the effectiveness of cytisine compared with 
that of existing cessation treatments.
TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 
(ACTRN12610000590066).