Eisenberg 2020.

Study characteristics
Methods	Design: 3‐arm RCT Recruitment: Community Setting: Canada Study start date: November 2016. Study end date: September 2019.
Participants	Total N: 376; Nicotine e‐cigarettes = 128; Non‐nicotine e‐cigarettes = 127; Counselling (control) = 121 47% female; mean age 52.66; mean cpd 21; mean FTND 6 (SD 2). Motivated to quit ‐ Yes Inclusion criteria: Active smoker, 10 or more cigarettes per day, on average, for the past year Age of 18 years or older Motivated to quit according to the Motivation To Stop Scale (MTSS) (level 5 or higher) Able to understand and to provide informed consent in English or French Likely to be available for follow‐up (1 year) Exclusion criteria: Medical condition with a prognosis < 1 year Current or recent cancer (less than 1 year in remission) Pregnant or lactating women Current or recent use (in the past 30 days) of any pharmacotherapy or behavioral therapy for smoking cessation (e.g. nicotine replacement Therapies, bupropion, varenicline, or counseling) Any e‐cigarette use (nicotine or non‐nicotine) in the past 60 days, or ever use of any e‐cigarette for more than 7 days consecutively History of psychosis, schizophrenia, or bipolar disorder Less than 1 month following a myocardial infarction, life‐threatening arrhythmia, severe or worsening angina pectoris, or cerebral vascular accident Use of any illegal drugs in the past year (excluding marijuana) Planned use of tobacco products other than conventional cigarettes (e.g. cigarillos, cigars, snuff, shisha, etc.) or marijuana during the study period
Interventions	EC: Cig‐a‐like Nicotine e‐cigarettes plus counseling: 12 weeks of e‐cigarettes. Rechargeable base with prefilled, disposable, tobacco‐flavored liquid cartridges (15 or 0 mg nicotine/mL), which were produced specifically for use in clinical studies (purchased from NJOY Inc, Scottsdale, Arizona). 21 cartridges at baseline with additional cartridges supplied as needed. Nicotine and nonnicotine e‐cigarettes were identical in appearance. Instructed to be used as desired. No schedule for e‐cigarette tapering, but participants were aware that they would return their e‐cigarettes after 12 weeks Participants received individual smoking cessation and relapse prevention counseling (minimum 30 minutes at baseline, 10 minutes during telephone follow‐ups, and 15 ‐ 20 minutes at clinic visits). Individualized quit plans Non‐nicotine e‐cigarettes plus counseling: As above with 0 mg nicotine/mL in liquid cartridge Counseling (control): Participants received individual smoking cessation and relapse prevention counseling (minimum 30 minutes at baseline, 10 minutes during telephone follow‐ups, and 15 ‐ 20 minutes at clinic visits). Individualized quit plans
Outcomes	Follow‐up was conducted by telephone at weeks 1, 2, 8, and 18, and at clinic visits at weeks 4, 12, 24, and 52 Self‐reported smoking (7‐day recall), adherence, and adverse events (AEs) were assessed during follow‐up contacts Biochemically‐validated 7‐day point prevalence smoking abstinence at 4, 12 and 24 weeks, defined as self‐reported abstinence in the past 7 days with exhaled carbon monoxide < 11 ppm At baseline: cpd; FTND; Glover‐Nilsson Smoking Behavioral Questionnaire (to assess behavioral dependence on smoking); and Beck Depression Inventory II (BDI‐II; to assess depressive symptoms)
Study funding	This trial was funded by the Canadian Institutes of Health Research (CIHR; funding reference No. 133727 and 155969). Both nicotine e‐cigarettes and nonnicotine e‐cigarettes were purchased from NJOY Inc (Scottsdale, Arizona)
Author declarations	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
Notes	New cessation and adverse event data for 2021 update. Previously listed as NCT02417467 (included with SAE data only)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible participants were randomized via an online central randomization system. The system used a computer‐generated randomization list containing permuted blocks of 6 and 9, stratified by center
Allocation concealment (selection bias)	Low risk	Participants, investigators, and study personnel were blinded to nicotine content in the e‐cigarette groups
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants, investigators, and study personnel were blinded to nicotine content in the e‐cigarette groups
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Participants, investigators, and study personnel were blinded to nicotine content in the e‐cigarette groups
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low numbers lost to follow‐up, treated as ITT
Selective reporting (reporting bias)	Low risk	Due to a prolonged and unforeseen delay in e‐cigarette manufacturing, enrolment was paused on 27 September 2019, and then terminated on 14 November 2019. Given reduced power, the timing of the primary endpoint was changed from 52 weeks to 12 weeks on 04 December 2019. No 12‐month follow‐up but this was for manufacturing reasons and was reported