A Randomised Controlled Trial Evaluating the Effectiveness and Tolerability of Step-up and Step-down Varenicline Therapy for Smoking Cessation: A Study Protocol

Abstract

Background: Varenicline remains the most effective medication for smoking cessation; however, discontinuation as a result of adverse events negatively impacts medication adherence, and the likelihood of a quit attempt being successful. Post-treatment cravings and withdrawal symptoms may also occur, increasing the likelihood of treatment failure, due to lapse and relapse after achieving initial abstinence. This protocol details a trial investigating changes in the effectiveness and tolerability of varenicline, when an extended step-up and step-down regimen are used.Methods: A phase four, randomised, double-blinded, placebo-controlled single-centre study with a treatment period of 16 weeks, and follow-up period of 12 weeks will be conducted. Up to 201 participants will be enrolled and allocated in a 1:1:1 ratio to a placebo-matching control group, step-up, or step-down intervention group, all receiving behavioural counselling and quitting advice. Participants will be contacted weekly during treatment and fortnightly during follow-up. Eligible participants are smokers over 18 years old, willing to quit smoking, are able to attend clinic visits, and have no uncontrolled or serious medical issues. Primary outcome measures are comparisons of biochemically confirmed continuous abstinence rates, 7-day point prevalence abstinence rates, and the frequency, severity and duration of adverse events, cravings and withdrawal symptoms. Secondary outcome measures are participant adherence to the study medication throughout treatment, and comparisons of changes in smoking satisfaction and reward. Effects of each regimen on smoking cessation will be assessed by logistic regression, with survival analyses used for a more precise estimate of when cessation occurs. Primary endpoints will then be compared using a general linear model. Australian New Zealand Clinical Trials Registry: ACTRN12616000802404p