Schematic diagram of the ECLAT study design.

<p>Smokers not currently attempting to quit smoking or wishing to do so in the next 30 days were randomized in three study groups<b>:</b> group A (receiving 12 weeks of 7.2 mg nicotine cartridges), group B (receiving 6-weeks of 7.2 mg nicotine cartridges and a further 6 weeks with 5.4 mg nicotine cartridges), and group C (receiving 12 weeks of no-nicotine cartridges). Participants in each group were prospectively reviewed for up to 52-weeks during which smoking habits, eCO levels, adverse events, vital signs, and product preference were assessed at each study visits. Additionally, saliva samples were collected at week-6 and at week-12 (closed triangles) for cotinine measurement in those who stated they had not smoked and with an eCO ≤7 ppm.</p

Time-course (at Week-6, -12, -24, and -52) of changes in the number of reducers and quitters in the ECLAT study (intention-to-treat analysis; all three study groups combined together).

<p>Time-course (at Week-6, -12, -24, and -52) of changes in the number of reducers and quitters in the ECLAT study (intention-to-treat analysis; all three study groups combined together).</p

Flow of participants.

<p>After screening for the study inclusion/exclusion criteria, a total of 300 regular smokers consented to participate and were included in the study<b>.</b> Participants were randomized into three separate study groups (A, B, and C). Participants randomized in <b>s</b>tudy group A received 12 weeks supply of “Original” 7.2 mg nicotine cartridges; those in study group B, two 6-week supplies of cartridges, one of the “Original” 7.2 mg nicotine cartridges and a further 6 weeks with supply of “Categoria” 5.4 mg nicotine cartridges; participants in study group C received 12 weeks supply of no-nicotine cartridges (i.e. control).</p

Time-course of changes in the median exhaled CO levels from baseline, separately for each study group.

<p>A significant reduction (per-protocol evaluation, p<0.0001, Wilcoxon signed-rank test) was observed at each study visits in all three study groups. When significant, between-group differences were indicated (Kruskal-Wallis test). The upper part of the figure illustrates the number of subjects attending each study visit.</p

Details of median (interquartile range - IQR) cartridge use at different time points for the total sample and separately for smoking failures, reducers, and quitters categories.

*<p>p values are relevant to the differences in the number of used cartridges among failures, reducers, and quitters subgroups at each time point (Kruskal-Wallis test).</p

Time-course of changes in the median number of cigarettes/day use from baseline, separately for each study group.

<p>A significant reduction (per-protocol evaluation, p<0.0001, Wilcoxon signed-rank test) was observed at each study visits in all three study groups. When significant, between-group differences were indicated (Kruskal-Wallis test). The upper part of the figure illustrates the number of subjects attending each study visit.</p

Reduction and quit rates at different time points, shown separately for each study group (intention-to-treat analysis).

*<p>p values are relevant to the differences in frequency distribution in reduction and quit rates among groups at each Study Visits (χ² test).</p

Image of the product tested in the study.

<p>The “Categoria” electronic cigarette is a three-piece model consisting of a disposable inhaler/mouthpiece (the cartridge), an atomizer and a rechargeable battery (the cigarette body). Disposable cartridges used in this study looked like tobacco cigarette’s filters containing an absorbent material saturated with a liquid solution of propylene glycol and vegetable glycerin in which different concentrations of nicotine or an aroma were dissolved. The cigarette body contains a rechargeable 3.7 V-90 mAh lithium-ion battery that activates the heating element in the atomizer.</p

General characteristics of ECLAT study sample at baseline.

<p>Legend: SD – standard deviation; IQR – interquartile range; Pack/yrs – pack-years; Cig/day – Cigarettes smoked per day; eCO – exhaled carbon monoxide; FTND – Fagerstrom Test of Nicotine Dependence; GN-SBQ- Glover-Nilsson Smoking Behavioral Questionnaire; BDI – Beck Depression Inventory; BAI – Beck Anxiety Inventory.</p><p>Data are reported for the overall sample and separately for each treatment group. Differences among groups were evaluated by χ² test for categorical variables, one-way analysis of variance (ANOVA) and Fisher protected LSD for parametric variables, and Kruskal-Wallis test for non parametric variables.</p>*<p>p = 0.04 between A and C groups (ANOVA).</p

Characteristics of enrolled sample (No. = 3,200).

<p>*χ² test</p><p>**one-way-ANOVA.</p><p>In BMI classification, overweight and obese children were defined following the gender- and age-specific cut-off points by Cole et Al[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127154#pone.0127154.ref015" target="_blank">15</a>]</p><p>Data are shown separately for asymptomatic subjects (No. = 2,393) for multiple regression analysis (Tables <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127154#pone.0127154.t003" target="_blank">3</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127154#pone.0127154.t004" target="_blank">4</a>) and symptomatic individuals (No. = 807) included in the analysis presented in Tables <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127154#pone.0127154.t007" target="_blank">7</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127154#pone.0127154.t008" target="_blank">8</a>.</p><p>Characteristics of enrolled sample (No. = 3,200).</p