E-cigarettes versus combination nicotine replacement therapy following a recent failed quit attempt: a pragmatic randomized trial through state tobacco quitlines.

Background: E-cigarettes have emerged as a potentially more effective and satisfying alternative to nicotine replacement therapy (NRT) for smokers who struggle to quit. Although quitlines are effective platforms for tobacco cessation, they have not incorporated e-cigarettes due to regulatory concerns and limited clinical evidence. We evaluated whether quitline-delivered counseling combined with e-cigarettes was more effective than counseling with NRT among adults who recently failed to quit using standard quitline services. Methods: We conducted a pragmatic, open-label, parallel-group randomised controlled trial with two U.S. state quitlines between October 2020 and January 2023. Adults [N = 350; 212 (61%) female & 248 (72%) white] who were still smoking after a recent quitline enrollment were randomised (1:1) to receive 8 weeks of either JUUL e-cigarettes or a combination of nicotine patch and lozenge, along with three counseling calls. The primary outcome was biochemically verified 7-day point prevalence smoking abstinence (7-day PPA) at 8 weeks. Analyses used an intent-to-treat approach; secondary outcomes included 12-week abstinence, prolonged abstinence, changes in smoking behavior, dependence, and adverse effects. Findings: At 8 weeks, 7-day PPA did not differ significantly between e-cigarette and NRT groups [25 (14.3%) of 175 and 17 (9.7%) of 175, respectively; OR 1.56; 95% CI 0.80-3.04; p = 0.19]. Both groups showed similar reductions in cigarette use and dependence. Adherence to counseling and assigned products was high. Adverse events were generally mild; cough and breathing difficulties were more frequently reported in the e-cigarette group and NRT participants reported more dizziness, sleeplessness, and allergies. Interpretation: Among quitline users with a recent failed quit attempt, e-cigarettes combined with quitline counseling were not more effective than combination NRT in increasing smoking abstinence after 8 weeks' follow-up. Funding: U.S. National Institute on Drug Abuse.