NCT04725656.

Study name	Concentration Impact Nicotine Salt (CINS)
Methods	Design: RCT
Participants	Estimated enrolment: 312 Inclusion criteria: Adult (≥ 18 years old) smokers (at least 5 TC per day for at least 12 months) Motivated to quit smoking as evidenced by signing the informed consent form at trial enrolment specifying that a target quit date will be set Saliva cotinine of > 50 ng/ml at screening Willing to participate in the trial even if allocated to the control group Ability to communicate well with the investigator and to understand and comply with the requirements of the study Signed informed consent form Exclusion criteria: Known hypersensitivity/allergy to a content of the e‐liquid Pregnancy or breast feeding Intention to become pregnant during the course of the study Regular use of EC or tobacco heating systems Use of NRT, varenicline, or bupropion in the month prior to the screening visit Smoke tobacco combined with marijuana and do not currently want to quit marijuana use Participation in an interventional trial within 30 days prior to the screening visit Legal incapacity or limited legal capacity at screening Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Interventions	Active Comparator: Active arm, low concentration (18 mg/mL) nicotine salt e‐liquids. Procedure: Smoking cessation counselling: Smoking cessation counselling at baseline, week 1, week 2 and week 4 Other: Open system vape device and nicotine salt e‐liquids; Ad libitum use of nicotine salt e‐liquids during 3 months Active Comparator: Active arm, high concentration (59 mg/mL) nicotine salt e‐liquids. Procedure: Smoking cessation counselling: Smoking cessation counselling at baseline, week 1, week 2 and week 4 Other: Open system vape device and nicotine salt e‐liquids; Ad libitum use of nicotine salt e‐liquids during 3 months Control group: Receive only smoking cessation counselling. Procedure: Smoking cessation counselling: Smoking cessation counselling at baseline, week 1, week 2 and week 4
Outcomes	Primary outcome: 7‐day point prevalence tobacco abstinence (in terms of non‐inferiority); Time Frame: 1 month. Defined as no smoking, i.e. "not a puff", self‐reported and confirmed by exhaled carbon monoxide (< 10 ppm) and urinary anabasine levels (< 3 ng/mL) when using low vs. high nicotine salt concentration e‐liquids Volume of e‐liquid used (in terms of superiority); Time Frame: 1 month; Volume of e‐liquid used when using low vs. high nicotine salt concentration e‐liquids Secondary outcome: 7‐day point prevalence tobacco abstinence (in terms of non‐inferiority); Time Frame: 1 month. Defined as no smoking, i.e. "not a puff", self‐reported and confirmed by exhaled carbon monoxide (< 10 ppm) and urinary anabasine levels (< 3 ng/mL) when using low vs. high nicotine salt concentration e‐liquids Volume of e‐liquid used (in terms of superiority); Time Frame: 1 month; Volume of e‐liquid used when using low vs. high nicotine salt concentration e‐liquids Liking/rating of trial product (active arms); Time Frame: 1 and 3 months. Questions regarding helpfulness in refraining from smoking, how satisfying and how good the e‐cigarette tastes compared to the tobacco cigarettes, if they would recommend the assigned trial product to another smoker, and any potential practical problems they might have with the handling Respiratory symptoms; Time Frame: Up to 12 months; Checklist with specific questions regarding shortness of breath, wheezing, cough or phlegm Adverse events; Time Frame: Up to 12 months; Checklist with specific questions regarding presence or absence of nausea, sleep disturbance, throat/mouth irritation or other Total nicotine amount vaped; Time Frame: 1 and 3 months Total volume of e‐liquid consumed; Time Frame: 1 and 3 months
Starting date	Estimated start date: 01 September 2021. Estimated primary completion date 30 December 2022. Estimated study completion date 30 June 2023
Contact information	Evangelia Liakoni, MD0041316325461 evangelia.liakoni@insel.ch
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