Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT

Background: Relapse remains an unresolved issue in smoking cessation. Extended stop smokingmedication use can help, but uptake is low and several behavioural relapse prevention interventionshave been found to be ineffective. However, opportunistic ‘emergency’ use of fast-acting nicotinereplacement treatment or electronic cigarettes may be more attractive and effective, and an onlinebehavioural Structured Planning and Prompting Protocol has shown promise. The present trial aimedto evaluate the clinical effectiveness and cost-effectiveness of these two interventions.Design: A randomised controlled trial.Setting: English stop smoking services and Australian quitlines, Australian social media and St Vincent’sHospital Melbourne, Fitzroy, VIC.Participants: Ex-smokers abstinent for at least 4 weeks, with some participants in Australia alsorecruited from 1 week post quit date. The planned sample size was 1400, but the trial was curtailedwhen 235 participants were recruited.Interventions: Participants were randomised in permuted blocks of random sizes to (1) oral nicotinereplacement treatment/electronic cigarettes to use if at risk of relapse, plus static text messages(n = 60), (2) the Structured Planning and Prompting Protocol and interactive text messages (n = 57),(3) oral nicotine replacement treatment/electronic cigarettes plus the Structured Planning and PromptingProtocol with interactive text messages (n = 58) or (4) usual care plus static text messages (n = 59).Outcome measures: Owing to delays in study set-up and recruitment issues, the study was curtailedand the primary outcome was revised. The original objective was to determine whether or not the twointerventions, together or separately, reduced relapse rates at 12 months compared with usual care.The revised primary objective was to determine whether or not number of interventions received(i.e. none, one or two) affects relapse rate at 6 months (not biochemically validated because of studycurtailment). Relapse was defined as smoking on at least 7 consecutive days, or any smoking in thelast month at final follow-up for both the original and curtailed outcomes. Participants with missingoutcome data were included as smokers. Secondary outcomes included sustained abstinence (i.e. nomore than five cigarettes smoked over the 6 months), nicotine product preferences (e.g. electroniccigarettes or nicotine replacement treatment) and Structured Planning and Prompting Protocol copingstrategies used. Two substudies assessed reactions to interventions quantitatively and qualitatively.The trial statistician remained blinded until analysis was complete.Results: The 6-month relapse rates were 60.0%, 43.5% and 49.2% in the usual-care arm, one-interventionarm and the two-intervention arm, respectively (p = 0.11). Sustained abstinence rates were 41.7%, 54.8%and 50.9%, respectively (p = 0.17). Electronic cigarettes were chosen more frequently than nicotinereplacement treatment in Australia (71.1% vs. 29.0%; p = 0.001), but not in England (54.0% vs. 46.0%;p = 0.57). Of participants allocated to nicotine products, 23.1% were using them daily at 6 months. Theonline intervention received positive ratings from 63% of participants at 6 months, but the majority ofparticipants (72%) completed one assessment only. Coping strategies taught in the Structured Planningand Prompting Protocol were used with similar frequency in all study arms, suggesting that theseare strategies people had already acquired. Only one participant used the interactive texting, andinteractive and static messages received virtually identical ratings.Limitations: The inability to recruit sufficient p articipants resulted in a lack of power to detectclinically relevant differences. Self-reported abstinence was not biochemically validated in the curtailedtrial, and the ecological momentary assessment substudy was perceived by some as an intervention.Conclusions: Recruiting recent ex-smokers into an interventional study proved problematic. Bothinterventions were well received and safe. Combining the interventions did not surpass the effects ofeach intervention alone. There was a trend in favour of single interventions reducing relapse, but it didnot reach significance and there are reasons to interpret the trend with caution