Effect of e-Cigarettes Plus Counseling vs Counseling Alone on Smoking Cessation: A Randomized Clinical Trial

Abstract

Importance: Electronic cigarettes (e-cigarettes) for smoking cessation remain controversial.

Objective: To evaluate e-cigarettes with individual counseling for smoking cessation.

Design, setting, and participants: A randomized clinical trial enrolled adults motivated to quit smoking from November 2016 to September 2019 at 17 Canadian sites (801 individuals screened; 274 ineligible and 151 declined). Manufacturing delays resulted in early termination (376/486 participants, 77% of target). Outcomes through 24 weeks (March 2020) are reported.

Interventions: Randomization to nicotine e-cigarettes (n = 128), nonnicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121) for 12 weeks. All groups received individual counseling.

Main outcomes and measures: The primary end point was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks, changed from 52 weeks following early termination. Participants missing data were assumed to be smoking. The 7 secondary end points, examined at multiple follow-ups, were point prevalence abstinence at other follow-ups, continuous abstinence, daily cigarette consumption change, serious adverse events, adverse events, dropouts due to adverse effects, and treatment adherence.

Results: Among 376 randomized participants (mean age, 52 years; 178 women [47%]), 299 (80%) and 278 (74%) self-reported smoking status at 12 and 24 weeks, respectively. Point prevalence abstinence was significantly greater for nicotine e-cigarettes plus counseling vs counseling alone at 12 weeks (21.9% vs 9.1%; risk difference [RD], 12.8 [95% CI, 4.0 to 21.6]) but not 24 weeks (17.2% vs 9.9%; RD, 7.3 [95% CI, -1.2 to 15.7]). Point prevalence abstinence for nonnicotine e-cigarettes plus counseling was not significantly different from counseling alone at 12 weeks (17.3% vs 9.1%; RD, 8.2 [95% CI, -0.1 to 16.6]), but was significantly greater at 24 weeks (20.5% vs 9.9%; RD, 10.6 [95% CI, 1.8 to 19.4]). Adverse events were common (nicotine e-cigarette with counseling: 120 [94%]; nonnicotine e-cigarette with counseling: 118 [93%]; counseling only: 88 [73%]), with the most common being cough (64%) and dry mouth (53%).

Conclusions and relevance: Among adults motivated to quit smoking, nicotine e-cigarettes plus counseling vs counseling alone significantly increased point prevalence abstinence at 12 weeks. However, the difference was no longer significant at 24 weeks, and trial interpretation is limited by early termination and inconsistent findings for nicotine and nonnicotine e-cigarettes, suggesting further research is needed.

Trial registration: ClinicalTrials.gov Identifier: NCT02417467.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Eisenberg reported receiving educational grants from Pfizer Inc for providing continuing medical education in cardiology. Dr Wilderman reported receiving financial compensation from Pfizer Inc for his involvement in a smoking cessation study using varenicline. Dr Filion reported receiving salary support from the Fonds de Recherche du Quebec, a William Dawson Scholar award from McGill University, and personal fees from Institut National D’excellence en Santé et Services Sociaux. No other disclosures were reported.

Figures

Figure 1.. Randomization and Follow-up of Study Participants

e-Cigarette indicates electronic cigarette. aSubgroups sum to greater than 425 because screened individuals could have more than 1 reason for exclusion. bPrecluding medical conditions included history of psychosis, schizophrenia, or bipolar disorder (n = 35; 6%); current cancer or in remission for less than 1 year (n = 22; 4%); condition with a prognosis of less than 1 year (n = 7; 1%); and less than 1 month following a major cardiac event (n = 5; 1%). cOther reasons included pregnant/lactating women (n = 3; 0.5%) and unable to provide informed consent in English or French (n = 2; 0.3%) dIncludes all participants. Participants were analyzed according to the group to which they were randomized. Participants who were lost to follow-up or withdrew were assumed to have returned to smoking at their baseline level. eFor participants who were lost to follow-up, vital status was obtained if possible from medical record review or alternate contact.

Figure 2.. Smoking Abstinence and Reduction by Treatment Group

Participants who withdrew consent or were lost to follow-up were considered to have returned to smoking at their baseline level. See Supplement 2 for results of all statistical comparisons. The primary end point was point prevalence abstinence at 12 weeks. All other reported smoking abstinence and reduction outcomes were prespecified secondary end points. A, Participants were considered abstinent if they abstained from smoking in the 7 days before the visit through a self-report of 0 cigarettes smoked/d, with an expired carbon monoxide reading less than or equal to 10 ppm at clinic visits at 4, 12, and 24 weeks. Expired carbon monoxide readings were available for 93%, 87%, and 77% of self-reported abstinent participants at 4, 12, and 24 weeks, respectively. B, Participants were considered continuously abstinent if they reported smoking 0 cigarettes in the 7 days before each follow-up since randomization, with expired carbon monoxide readings less than or equal to 10 ppm at clinic visits at 4, 12, and 24 weeks. Expired carbon monoxide readings were available for 78%, 82%, and 78% of continuously self-reported abstinent participants at 4, 12, and 24 weeks, respectively. C, Change in the mean number of self-reported cigarettes smoked per day in the past week. e-Cigarette indicates electronic cigarette.