Colin Howe

Electronic cigarettes for smoking cessation: a randomised controlled trial

BACKGROUND Electronic cigarettes (e-cigarettes) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts. We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit. METHODS We did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (≥18 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [Māori; Pacific; or non-Māori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or ≤5 Fagerström test for nicotine dependence]) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks after quit day, with low intensity behavioural support via voluntary telephone counselling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000866000. FINDINGS 657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1·51 [95% CI -2·49 to 5·51]; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [95% CI -2·29 to 8·61]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product. INTERPRETATION E-cigarettes, with or without nicotine, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels. FUNDING Health Research Council of New Zealand.

Study protocol for a randomised controlled trial of electronic cigarettes versus nicotine patch for smoking cessation.

BackgroundElectronic cigarettes (e-cigarettes or electronic nicotine delivery systems [ENDS]) are electrically powered devices generally similar in appearance to a cigarette that deliver a propylene glycol and/or glycerol mist to the airway of users when drawing on the mouthpiece. Nicotine and other substances such as flavourings may be included in the fluid vaporised by the device. People report using e-cigarettes to help quit smoking and studies of their effects on tobacco withdrawal and craving suggest good potential as smoking cessation aids. However, to date there have been no adequately powered randomised trials investigating their cessation efficacy or safety. This paper outlines the protocol for this study.Methods/designDesign: Parallel group, 3-arm, randomised controlled trial. Participants: People aged ≥18 years resident in Auckland, New Zealand (NZ) who want to quit smoking. Intervention: Stratified blocked randomisation to allocate participants to either Elusion™ e-cigarettes with nicotine cartridges (16 mg) or with placebo cartridges (i.e. no nicotine), or to nicotine patch (21 mg) alone. Participants randomised to the e-cigarette groups will be told to use them ad libitum for one week before and 12 weeks after quit day, while participants randomised to patches will be told to use them daily for the same period. All participants will be offered behavioural support to quit from the NZ Quitline. Primary outcome: Biochemically verified (exhaled carbon monoxide) continuous abstinence at six months after quit day. Sample size: 657 people (292 in both the nicotine e-cigarette and nicotine patch groups and 73 in the placebo e-cigarettes group) will provide 80% power at p = 0.05 to detect an absolute difference of 10% in abstinence between the nicotine e-cigarette and nicotine patch groups, and 15% between the nicotine and placebo e-cigarette groups.DiscussionThis trial will inform international debate and policy on the regulation and availability of e-cigarettes. If shown to be efficacious and safe, these devices could help many smokers as an alternative smoking cessation aid to standard nicotine products.Trial registrationAustralian NZ Clinical Trials Registry (ACTRN12610000866000).

The combined effect of very low nicotine content cigarettes, used as an adjunct to usual Quitline care (nicotine replacement therapy and behavioural support), on smoking cessation: a randomized controlled trial

AIM To determine the combined effect of very low nicotine content (VLNC) cigarettes and usual Quitline care [nicotine replacement therapy (NRT) and behavioural support] on smoking abstinence, in smokers motivated to quit. DESIGN Single-blind, parallel randomized trial. SETTING New Zealand. PARTICIPANTS Smokers who called the Quitline for quitting support were randomized to either VLNC cigarettes to use whenever they had an urge to smoke for up to 6 weeks after their quit date, in combination with usual Quitline care (8 weeks of NRT patches and/or gum or lozenges, plus behavioural support) or to usual Quitline care alone. MEASUREMENTS The primary outcome was 7-day point-prevalence smoking abstinence 6 months after quit day. Secondary outcomes included continuous abstinence, cigarette consumption, withdrawal, self-efficacy, alcohol use, serious adverse events and views on the use of the VLNC cigarettes at 3 and 6 weeks and 3 and 6 months. FINDINGS A total of 1410 participants were randomized (705 in each arm), with a 24% loss to follow-up at 6 months. Participants in the intervention group were more likely to have quit smoking at 6 months compared to the usual care group [7-day point-prevalence abstinence 33 versus 28%, relative risk (RR) = 1.18, 95% confidence interval (CI): 1.01, 1.39, P = 0.037; continuous abstinence 23 versus 15%, RR = 1.50, 95% CI: 1.20, 1.87, P = 0.0003]. The median time to relapse in the intervention group was 2 months compared to 2 weeks in the usual care group (P < 0.0001). CONCLUSIONS Addition of very low nicotine content cigarettes to standard Quitline smoking cessation support may help some smokers to become abstinent.

Abrupt nicotine reduction as an endgame policy: a randomised trial

Objective To determine if smokers unmotivated to quit reduce usual cigarette consumption when cigarettes priced according to nicotine content are made available. Methods Randomised, parallel-group, trial (ACTRN12612000914864) undertaken in Wakatipu/Central Otago, New Zealand. Dependent adult daily smokers unmotivated to quit were randomly allocated to an intervention group provided with 12 weeks supply of free very low nicotine content (VLNC) cigarettes, or to a control group, who were free to purchase their usual cigarette brand over the same period. The primary outcome was change from baseline in the daily mean number of usual cigarettes smoked over the previous week, measured at 12 weeks. Secondary outcomes at 6 and 12 weeks included cigarettes smoked per week (also measured at weeks 1–6 and 9), salivary cotinine, tobacco dependence, smoking satisfaction/craving, behavioural addiction to smoking, autonomy over smoking, motivation to stop, price at which participants would purchase VLNC cigarettes, quitting and adverse events. Results Thirty-three smokers were randomised (17 intervention, 16 control). A NZ

Electronic cigarettes and smoking cessation: a quandary? – Authors' reply

15 price differential (per pack of 20) based on nicotine content led to a halving in the mean number of cigarettes smoked per day over the previous week, a reduction in tobacco dependence and an increase in quitting. Intervention participants smoked a similar total number of cigarettes (usual plus VLNC) as those in the control group, exposing them to a similar level of toxicants. Conclusions Smokers unmotivated to quit reduce their usual cigarette consumption (and thus nicotine exposure) when VLNC cigarettes are made available at a significantly reduced price.

Study protocol for a randomised trial of nicotine-free cigarettes as an adjunct to usual NRT-based cessation practice, in people who wish to stop smoking

408 www.thelancet.com Vol 383 February 1, 2014 on to outline statistically insignifi cant trends in secondary outcome measures favouring the nicotine e-cigarette group as further support for the apparent superiority of e-cigarettes. By contrast, a statistically insignificant increase in adverse events in the nicotine e-cigarettes group is glossed over as “no diff erence” to nicotine patches. In view of the evident lack of benefi t, it is concerning to note that 38% of those who stopped smoking in the nicotine e-cigarette group continued using e-cigarettes, and 29% of the ongoing smokers were potentially supplementing traditional cigarettes with e-cigarettes. This fi nding might be good news for tobacco companies developing markets, but not for global public health. In that context it is appropriate to recall that evidence shows that most (54–69%) smokers quit without pharmacological aids. In view of the costs of pharmacological aids, particularly for developing countries, we propose prioritising investment in investigating approaches which can be delivered globally.

Pre-cessation nicotine replacement therapy: pragmatic randomized trial

BackgroundCurrent smoking cessation treatments focus on addressing the pharmacological dependence of smokers on nicotine. However, new strategies are needed that address both nicotine dependence and the psychological dependence on cigarettes as the source of nicotine. Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates. This paper describes the protocol for a large randomised-controlled trial to test the effect of using nicotine-free cigarettes together with NRT on long-term quit rates.Methods/designThis single-blind, randomised trial aims to recruit 1,410 participants through the national telephone-based Quitline service in New Zealand. Participants in the treatment arm will be asked to stop smoking nicotine-containing cigarettes on their chosen Quit day and smoke ad libitum nicotine-free (Quest 3) cigarettes for six weeks. At the same time people in this group will be asked to start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Participants in the control arm will be asked to stop smoking completely on their chosen Quit day and start using NRT patches, gum and/or lozenges (as recommended by Quitline) for eight weeks. Data collection will occur at baseline, three and six weeks, and three and six months after Quit day. The primary outcome is the proportion of participants who self-report seven-day point prevalence abstinence at six months since Quit date.DiscussionSmoking prevalence in New Zealand has changed little in recent years (particularly in Māori, the indigenous people of New Zealand) and additional options for smokers who want to quit are needed. Although a variety of methods are available to help, many are expensive, have side effects, and despite their use most quit attempts still fail. This trial will test the balance of benefits and risks of a new strategy for people to overcome nicotine dependence. Since smoking is the leading cause of lost healthy life years in New Zealand, if proven effective this strategy is likely to have substantial public health benefits.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000410358