EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study

Abstract

Background: Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a 'smoking' experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model ('Categoria'; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n = 100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n = 100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n = 100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed.

Results: Declines in cig/day use and eCO levels were observed at each study visits in all three study groups (p<0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants' perception and acceptance of the product under investigation was satisfactory.

Conclusion: In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects.

Trial registration: ClinicalTrials.gov NCT01164072 NCT01164072.

Figure 1. Flow of participants.

After screening for the study inclusion/exclusion criteria, a total of 300 regular smokers consented to participate and were included in the study. Participants were randomized into three separate study groups (A, B, and C). Participants randomized in study 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).

Figure 2. Image of the product tested in the study.

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.

Figure 3. Schematic diagram of the ECLAT study design.

Smokers not currently attempting to quit smoking or wishing to do so in the next 30 days were randomized in three study groups: 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.

Figure 4. Time-course of changes in the median number of cigarettes/day use from baseline, separately for each study group.

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.

Figure 5. Time-course of changes in the median exhaled CO levels from baseline, separately for each study group.

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.

Figure 6. 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).

Figure 7. Box plots representation of the changes in saliva cotinine levels measured at week-6 and at week-12 in those who stated they did not smoke and with an eCO≤7 ppm; no significant difference between groups A and B at both time points was found (Mann-Whitney U test).

Bars indicate (from the bottom to the top) 10^th, 25^th, 50^th (median), 75^th, and 90^th percentiles. Values below 10^th and above 90^th percentiles (outliers) are shown as circles.

Figure 8. Time-course of changes in the frequency of the five most commonly reported adverse events (AEs) from baseline, separately for each study group.

On Y-axis, the number of subjects reporting AEs is depicted. Compared to baseline, a significant reduction in frequency of cough, dry mouth, shortness of breath, and headache was observed at each study visits in all three study groups (per-protocol evaluation, p<0.001, χ² test). No difference was found in frequency distribution of AEs among study groups (χ² test).