Effectiveness and safety of nicotine patches combined with e-cigarettes (with and without nicotine) for smoking cessation: study protocol for a randomised controlled trial

INTRODUCTION: Evidence indicates e-cigarettes can help people quit smoking; however, more confirmatory trials are needed. To date, no trials have evaluated the effectiveness and safety of combining nicotine patches with e-cigarettes (with and without nicotine) for smoking cessation. METHODS AND ANALYSIS: This study is a pragmatic, three-arm, community-based, single-blind, randomised trial undertaken in New Zealand. Eligible participants are daily/non-daily smokers, aged ≥18 years, naive e-cigarette users and motivated to quit smoking in the next 2 weeks. Participants (n=1809), recruited using multi-media advertising, are randomised to 14 weeks of (1) 21 mg nicotine patches (n=201); (2) 21 mg nicotine patches+18 mg/mL nicotine e-cigarette (n=804); or (3) 21 mg nicotine patches+nicotine free e-cigarette (n=804). Participants receive weekly withdrawal-oriented behavioural support calls for 6 weeks post-randomisation. The primary outcome is self-reported biochemically verified continuous abstinence (CA) at 6 months post quit-date. The primary comparison is nicotine patch + nicotine e-cigarette versus nicotine patch + nicotine free e-cigarette, and the secondary comparison is nicotine patch versus nicotine patch +nicotine e-cigarette (90% power, p=0.05, to detect an absolute difference in 6 month CA rates of 8% and 15% respectively). Secondary outcomes, collected by phone interview at quit date, then 1, 3, 6 and 12 months post-quit date, include self-reported CA, 7 day point prevalence abstinence, cigarettes per day (if smoking, or when smoking for non-daily smokers), time to relapse (if returned to smoking), belief in ability to quit, use of other cessation support, side effects/serious adverse events, treatment compliance, seeking additional support around e-cigarette use, daily use of both e-cigarettes and cigarettes, use of treatment past 14 weeks, views on treatment and recommendation to others, weight and cost-per-quitter. ETHICS AND DISSEMINATION: The Northern A Health and Disability Ethics Committee approved the trial. Findings will be disseminated through publication, conference/meeting presentations, and media. TRIAL REGISTRATION NUMBER: NCT02521662; Pre-results.