The effectiveness, safety and cost‐effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non‐inferiority trial

Abstract

Background and aimsSmoking cessation medications are effective, but often underutilized because of costs and side effects. Cytisine is a plant‐based smoking cessation medication with more than 50 years of use in central and eastern Europe. While cytisine has been found to be well‐tolerated and more effective than nicotine replacement therapy, direct comparisons with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost‐effectiveness of cytisine compared with varenicline.DesignTwo‐arm, parallel group, randomized, non‐inferiority trial, with allocation concealment and blinded outcome assessment.SettingAustralian population‐based study.ParticipantsAdult daily smokers (n = 1266) interested in quitting will be recruited through advertisements and Quitline telephone‐based cessation support services.Intervention and comparatorEligible participants will be randomized (1 : 1 ratio) to receive either cytisine capsules (25‐day supply) or varenicline tablets (12‐week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10–12‐minute sessions).MeasurementsAssessments will be undertaken by telephone at baseline, 4 and 7 months post‐randomization. Participants will also be contacted twice (2 and 4 weeks post‐randomization) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self‐reported 6‐month continuous abstinence from smoking, verified by carbon monoxide at 7‐month follow‐up. We will also evaluate the relative safety and cost‐effectiveness of cytisine compared with varenicline. Secondary outcomes will include self‐reported continuous and 7‐day point prevalence abstinence and cigarette consumption at each follow‐up interview.CommentsIf cytisine is as effective as varenicline, its lower cost and natural plant‐based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives world‐wide.

The efficacy and safety of varenicline alone versus in combination with nicotine lozenges for smoking cessation among hospitalised smokers (VANISH): study protocol for a randomised, placebo-controlled trial

“…Participants with a CO level <6 ppm will be considered abstinent. 16 38 Sensitivity analysis will be performed using a higher CO cut-off of <10 ppm. 39 …”

“…13 In attempts to improve smoking cessation rates, new combinations of existing smoking cessation therapies have been evaluated. [14][15][16] Current research suggests that varenicline may not fully saturate the nicotinic acetylcholine receptors in the brain. 14 This in turn leads to only a partial attenuation of nicotine cravings.…”

Current pharmacologic treatments for smoking cessation and new agents undergoing clinical trials

“…A two-arm, parallel-group, randomized, non-inferiority trial is in progress to evaluate the efficacy, safety, and cost-effectiveness of cytisine compared with varenicline for smoking cessation. 92…”

“…A two-arm, parallel-group, randomized, non-inferiority trial is in progress to evaluate the efficacy, safety, and cost-effectiveness of cytisine compared with varenicline for smoking cessation. 92 Other agents Clinical trials for other agents are summarized in Table 1. Although cigarettes represent ~90% of tobacco/nicotine use, the market for 'e-cigarettes' is growing.…”

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis

“…Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae). 12 It has been used to as a partial agonist of high-affinity acetylcholine receptors to withdraw nicotine cessation. 13 From the former research, we found that Cytisine has several pharmacological functions, such as anti-depressant like property, 14 anti-diabetes, 15 antivirus, 16 against human influenza virus A (H1N1) 16 and against cerebral ischemia-reperfusion 17 properties and so on.…”