NCT03630614

Randomized Trial of Electronic Cigarettes With or Without Nicotine in Smoking Cessation.

A Randomized, Placebo Controlled, Double Blind, Double Dummy, Multicenter Trial Comparing Electronic Cigarettes With Nicotine to Varenicline and to Electronic Cigarettes Without Nicotine.

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 650 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Background: Electronic cigarettes (EC) mainly containing nicotine (88-95 % of users) are widely and growingly used worldwide. It is estimated that there were 1.7 million daily users in France in 2016. Although the number of publications about its use is increasing exponentially, there are no evidence based, unbiased, head-to-head comparison data about its efficacy as an aid to smoking cessation. As of today, only two head-to-head randomized studies have been published, both reported negative results at the main endpoint but they used first and second generation EC delivering nicotine with low or unknown bioavailability. Recent EC deliver nicotine with largely improved bioavailability. One of the randomized studies compared EC with and without nicotine to nicotine patch and reported similar smoking cessation rate at main outcome. However, there is no published, double blind study comparing EC use with a well-studied, licensed smoking cessation medication. Superiority of EC with nicotine compared to EC without nicotine and to a reference smoking cessation medication while collecting also straightforward information about safety, would allow proposing EC with nicotine to the large population of smokers who intend to quit and situate it among the approved smoking cessation treatments. The clinical study's hypothesis: EC containing nicotine can be considered as a nicotine replacement therapy having, probably, a better bioavailability of nicotine than the marketed pharmaceutical NRTs, first line medications of smoking cessation. It is therefore of interest to compare EC containing nicotine to EC without nicotine but also to a reference medication with demonstrated efficacy in smoking cessation. We hypothesize that EC with nicotine provides a higher smoking abstinence rate than EC without nicotine and may be as good as varenicline, our reference medication.

Detailed description

This is a randomized, placebo controlled, multicenter, double dummy, parallel groups, phase III type pivotal trial. Included participants are randomly assigned to one of the 3 groups: A) Control group: Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline: placebo condition B) Experimental group: Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline: ECwN condition C) Reference group: ECwoN plus varenicline tablets: varenicline condition Ratio: A:B:C= 1:3:3 Each participant uses an EC and 2x2 tablets per day. Group allocation is stratified by age at cut off of 45 years. Enrolment is initiated by two ways: • Potential participants aware of the study register at the study's recruitment website; call in or send an email followed by a phone screen. The screening starts with the participant's information about the study's aims, constraints, benefits and risks. A maximum one week delay of reflection is allowed if the potential participant is asking for a delay to sign his/her consent form. After screening, an appointment for the inclusion visit is provided at the closest investigation center. • Referred or self-referred potential participants consulting for smoking cessation are proposed an inclusion visit. The participant is informed that in this study, the smoking cessation shall occur within 15 days following the signature of the written consent. Baseline visit = inclusion visit = V0 The Inclusion visit can immediately follow the screening visit if the participant does not need time for reflection. The investigator checks the inclusion and exclusion criteria and if the participant is conform to them, the investigator collects informed written consent from the participant and he/she is included in the trial. The randomization can immediately follow the inclusion. A target quit date (TQD) is defined together with the participant. The TQD defines the date when the randomized participant stops smoking. This is the starting date of the post-quit period. Start of treatment should occur within 7 days after the randomization visit. All treatments are launched one week before the TQD. During this period smoking conventional cigarettes is allowed. Follow-up visits : Visit 1 to Visit 6 Target quit date (TQD) should occur between 7 and 15 days after randomization. The first post-quit date visit (Visit 1)is at Week 2 after TQD i.e. 3 weeks after treatment initiation = Day 21 after treatment initiation. Visit 2 is at Week 4 after TQD i.e. 5 weeks after treatment initiation = Day 35 after treatment initiation. Visit 3 is at Week 8 after TQD i.e. 9 weeks after treatment initiation = Day 63 after treatment initiation. Visit 4 is at Week 10 after TQD i.e. 11 weeks after treatment initiation = Day 77 after treatment initiation. Visit 5 is at Week 12 after TQD i.e. 13 weeks after treatment initiation = Day 91 after treatment initiation. Visit 6 is at Week 24 after TQD i.e. 25 weeks after treatment initiation = Day 175 after treatment initiation. The visits should be realized +/- 5 days with respect to the planned date of the visits. End of study visit The end of research visit is the Visit 6, at week 24 after TQD. This visit is identical to the previous follow up visits.

Conditions

• Smoking Cessation
• Smoking, Cigarette
• Electronic Cigarette

Interventions

Type	Name	Description
DRUG	Electronic cigarette without nicotine (ECwN) plus active varenicline tablets	The ECwN group use EC liquids containing 0 mg/mL of nicotine. Because nicotine delivery can be adjusted according to the user's need, all participants are able to adjust their individual nicotine dose by varying the wattage of their EC, by varying puff frequency and puff volume similarly as they are doing (or used to do) with conventional cigarettes. EC device: Mini iStick kit (20 W) Eleaf Clearomiser :GS Air M with resistance of 1.5 ohm, the clearomiser's Pyrex window is of blue colour not allowing to distinguish an eventual coloration of the e-liquid containing nicotine. Liquids for EC use are delivered in white opaque 10 mL vials not allowing to distinguish the color of the liquid. Varenicline, Champix® 0.50 mg tablets Posology of vareniclin follows varenicline's monograph.
DRUG	Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline	The ECwoN group receives EC liquids with 0 mg/mL of nicotine on a double blind manner (in identical non-transparent refill bottles of 10 mL). Placebo of varenciline The placebo of varenicline is presented as a capsular-shaped, biconvex, white film-coated tablet. Posology of varenicline or its placebo follows varenicline's monograph.
DRUG	Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline	The ECwN group use EC liquids containing 12 mg/mL of nicotine. Placebo of varenciline The placebo of varenicline is presented as a capsular-shaped, biconvex, white film-coated tablet. Posology of varenicline or its placebo follows varenicline's monograph.

Timeline

• Start date: 2018-10-17
• Primary completion: 2029-02-01
• Completion: 2029-12-01
• First posted: 2018-08-15
• Last updated: 2025-12-29

Locations

1 site across 1 country: France