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

Chris Bullen 0 Jonathan Williman 2 Colin Howe 0 Murray Laugesen 1 Hayden McRobbie 3 Varsha Parag 0 Natalie Walker 0 0 National Institute for Health Innovation, School of Population Health, The University of Auckland , Private Bag 92019, Auckland 1142 , New Zealand 1 Health New Zealand Ltd , Lyttelton, Christchurch , New Zealand 2 Department of Public Health and General Practice, University of Otago , Christchurch , New Zealand 3 Queen Mary University of London, Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry , Charterhouse Square, London , UK Background: Electronic 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/design: Design: 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. Discussion: This 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 registration: Australian NZ Clinical Trials Registry (ACTRN12610000866000). - Background Most smokers want to quit and make attempts to do so but the majority of these attempts fail largely because of their dependence on nicotine and non-nicotine sensory and behavioural cues that reinforce their smoking behaviour [1]. Psychological and pharmacological smoking cessation treatments help smokers quit and are one of the most cost-effective health interventions available [2]. Indeed, nicotine replacement therapy (NRT) almost doubles quit rates irrespective of the level of additional behavioural support [3]. Nevertheless, absolute long-term quit rates with NRT are low: typically, fewer than 20% of people quitting with NRT plus behavioural support are still abstinent at 12 months [3]. Even the most rapid-acting and highest strength NRT products do not deliver nicotine in doses or at the same speed as cigarettes [4]. With the possible exception of the nicotine inhalator, neither do they replace the sensory and behavioural cues associated with cigarette use. Indeed, many smokers find available NRTs unhelpful, unpleasant or difficult to use and want more product choice [5]. Electronic nicotine delivery systems (ENDS), more commonly known as electronic cigarettes (hereafter abbreviated to 'e-cigarettes' or 'e-cigs'), are so-called because of their physical resemblance to a standard tobacco cigarette and their electronic vapourgenerating mechanism. In 2004 a Beijing-based company, Ruyan Group (Holdings) Ltd, patented and launched the first of these devices [6]. Many other manufacturers have since made similar devices. All contain a mouthpiece, a micro-electrical circuit, a vaporiser, and a rechargeable lithium ion battery. The solution in replaceable cartridges or used to fill a reservoir in some models typically contains a solution of humectants (e.g. propylene glycol and/or glycerol), and nicotine and flavourings. When a user draws air through the e-cigarette the micro-electrical circuit activates an electric coil to heat and vaporise a small amount of the nicotine solution, creating a visible cloud of mist that may be inhaled by the user [7]. It has been hypothesised that e-cigarettes could be more effective than NRT at helping people quit smoking by delivering nicotine together with mimicking the physical, sensory and behavioural aspects of cigarette use [1,8]. In international online surveys one of the key reasons people report buying e-cigarettes is to help quit smoking [9,10]. In 2008 we undertook the first study of the effect of the e-cigarettes on desire to smoke and withdrawal symptoms and found that they were as effective as the NRT inhaler on reducing withdrawal but more pleasant and acceptable to use [8]. Further research has generally supported these early findings, and none to date have found evidence of harm [6]. We also found that the speed of nicotine delivery and serum levels obtained was substantially less than tobacco cigarettes. This has been corroborated with other brands by other research groups [11,12]. A related question is the extent to which any quitting assistance provided by e-cigarettes might be attributable simply to the behavioural replacement they provide, as suggested by a study of a nicotinefree inhaler device by Capponeto et al. [13]. This is relevant to countries such as New Zealand where e-cigarettes are available for sale over the counter but without cartridges containing nicotine. E-cigarette sales are increasing rapidly: in the US alone there are an estimated 2.5 million users with sales of $300 million a year [14]. Internet search volumes have surpassed search volumes for both NRT and varenicline in the UK, US and Canada [15]. Despite this evidence of consumer demand, there are mixed views in the tobacco control community as to what role, if any, e-cigarettes might play in helping smokers to cease tobacco use. Strong concerns have been expressed over their potential to be a gateway to tobacco smoking, the safety of the inhaled vapours and ability of the devices to deliver nicotine as claimed [16-18]. Although a few studies have been conducted that show promise for the potential of e-cigarettes as cessation aids [19-21], no (...truncated)