NCT03589989.

Study name	The ESTxENDS Trial‐ Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E‐cigarette) as an aid for smoking cessation. (ESTxENDS)
Methods	Randomized, parallel‐assignment, open‐label trial Setting: Switzerland Recruitment: Not specified
Participants	Estimated Enrolment: 1172 Inclusion criteria: Informed consent as documented by signature Persons aged 18 or older Currently smoking 5 or more cigarettes a day for at least 12 months Willing to try to quit smoking within the next 3 months Persons providing a valid phone number, a valid email address and/or a valid postal address. Exclusion criteria: Known hypersensitivity or allergy to contents of the e‐liquid Participation in another study with investigational drug within the 30 days preceding the baseline visit and during the present study where interactions are to be expected Women who are pregnant or breastfeeding Intention to become pregnant during the course of the scheduled study intervention, i.e. within the first 6 months of the study Persons having used ENDS regularly in the 3 months preceding the baseline visit Persons having used nicotine replacement therapy (NRT) or other medications with demonstrated efficacy as an aid for smoking cessation such as varenicline or bupropion within the 3 months preceding the baseline visit Persons who cannot attend the 6‐month follow‐up visit for any reason Cannot understand instructions delivered in person or by phone, or otherwise unable to participate in study procedures
Interventions	a) ENDS (vaporizer/e‐cig) and smoking cessation counselling will receive: ENDS and nicotine‐containing e‐liquids, which they will be allowed to use ad libitum Smoking cessation counselling: provided in person at the first clinical visit and then over the phone at the target quit date 1 week later and again at weeks 2, 4 and 8 after the target quit date. After 6 months, participants will be asked to come to a final clinical visit Participants will be allowed to additionally use nicotine replacement therapy b) Control group will receive smoking cessation counselling only as provided for a). Participants will be allowed to additionally use nicotine replacement therapy
Outcomes	Primary outcome: Continuous smoking abstinence at 6 months post‐quit date measured by: Self‐report of having smoked no cigarettes from quit date, validated by urinary levels of anabasine. If anabasine is missing, validation by exhaled carbon monoxide (CO). Seconday outcomes: Continuous smoking abstinence at 6 months post‐quit date Self‐report of having smoked no cigarettes from quit date, validated by urinary levels of NNAL (4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled carbon monoxide (CO) Self‐reported smoking abstinence allowing a 2‐week`grace period' at 4, 8 weeks and 6 months post quit date Validated smoking abstinence allowing a 2‐week`grace period at 6 months post quit date validated by urinary levels of anabasine. If anabasine is missing validation by exhaled CO validated by urinary levels of NNAL (4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled CO Self‐reported smoking abstinence allowing up to 5 cigarettes at 1, 2, 4, 8 weeks and 6 months post‐quit date Validated smoking abstinence allowing up to 5 cigarettes at 6 months post‐quit date: validated by urinary levels of anabasine. If anabasine is missing validation by exhaled CO validated by urinary levels of NNAL (4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled CO Self‐reported 7‐day PPA at 1, 2, 4, 8 weeks and 6 months post‐quit date Validated 7‐day PPA at 6 months post‐quit date Confirmation of having smoked no cigarettes in the past 7 days, validated by urinary levels of anabasine. If anabasine is missing validation by exhaled CO Confirmation of having smoked no cigarettes in the past 7 days, validated by urinary levels of NNAL (4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled CO Number of cpd at baseline, target quit date, 1, 2, 4, 8 weeks and 6 months post‐quit date, self‐reported Change in number of cpd at baseline, 6 months post‐quit date, self‐reported. Successful reduction defined as 50% reduction in cpd Use of any other smoking cessation products (NRT) at 1, 2, 4, 8 weeks and 6 months post‐quit date, self‐reported Withdrawal at baseline and 6 months Fagerström Test for Nicotine Dependence at baseline and 6 months Swiss EQ‐5D at baseline and 6 months Use of any ENDS at 1, 2, 4, 8 weeks and 6 months post‐quit date, self‐reported Most common adverse events using ENDS at 1, 2, 4, 8 weeks and 6 months post‐quit date
Starting date	16 July 2018
Contact information	Reto Auer, reto.auer@biham.unibe.ch Anna Schöni, anna.schoeni@biham.unibe.ch
Notes	Linked trials: NCT03603340; NCT03603353; NCT03612336; NCT03612375; NCT03612453; NCT03612544; NCT03632421; NCT03938298