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

NCT03630614 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: P150952J2017-003588-37
• Study Type: interventional
• Target: 650
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Smoking Cessation; Smoking, Cigarette; Electronic Cigarette

Keywords

smokers; electronic cigarette; nicotine; varenicline; randomized; double blind; double dummy

Outcome Measures

Primary Outcomes (1)

• Continuous smoking abstinence rate

  Abstinence from conventional/combustible cigarettes during the last 4 weeks (weeks 9 to 12) of the treatment period of 3 months defined at Visit 4 AND Visit 5 as self-report of no smoking during the previous 2 weeks confirmed by expired air CO ≤ 8 ppm.

  Weeks 9 to 12

Secondary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).

  From randomisation up to end of study (Week 24 after target quit date).

• Point prevalence abstinence rate: 7-day smoking abstinence at each visit.

  From randomisation up to end of study (Week 24 after target quit date).

• Time to relapse to smoking after the predefined quit day.

  From randomisation up to end of study (Week 24 after target quit date).

• Change in cigarettes/day consumption

  From randomisation up to end of study (Week 24 after target quit date).

• French Tobacco Craving Questionnaire of 12 items (FTCQ-12)

  From randomisation up to end of study (Week 24 after target quit date).

Study Arms (3)

Electronic cigarette condition

EXPERIMENTAL

Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline

Drug: Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline

Varenicline condition

ACTIVE COMPARATOR

Reference group: Electronic cigarette without nicotine (ECwoN) plus active varenicline tablets

Drug: Electronic cigarette without nicotine (ECwN) plus active varenicline tablets

Placebo condition

PLACEBO COMPARATOR

Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline

Drug: Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline

Interventions

Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline DRUG

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.

Also known as: Placebo condition

Placebo condition

Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline DRUG

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.

Also known as: Electronic cigarette condition

Electronic cigarette condition

Electronic cigarette without nicotine (ECwN) plus active varenicline tablets DRUG

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.

Also known as: Vareniclin condition

Varenicline condition

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Smokers smoking at least 10 cigarettes/day (factory made or roll-your-own) in the past year
• Aged 18 to 70 years
• Motivated to quit defined as a score \> 5 on a visual rating scale ranging from 0 (not motivated at all) to 10 (extremely motivated)
• Signed written informed consent
• Understanding and speaking French
• Women of childbearing age can be included if they use an effective contraceptive method: either hormonal contraception or an intrauterine device started at least one month before the first research visit
• Individual affiliated to a health insurance system as defined by the sponsor (except Aide Médicale d'État =AME)
• Previous failure of nicotine replacement therapy for smoking cessation

You may not qualify if:

• any unstable disease condition within the last 3 months defined by the investigator as major change in symptoms or treatments such as 1.1.recent myocardial infarction, 1.2.unstable or worsening angina 1.3.severe cardiac arrhythmia 1.4.unstable or uncontrolled arterial hypertension 1.5.recent stroke 1.6.cerebrovascular disease 1.7.obliterative peripheral arterial disease 1.8.cardiac insufficiency 1.9.diabetes 1.10.hyperthyroidism 1.11.pheochromocytoma 1.12.severe hepatic insufficiency 1.13.history of seizures 1.14.severe depression 1.15.chronic obstructive pulmonary disease (COPD)
• any life threatening condition with life-expectancy of less than 3 months
• alcohol use disorder defined as a score ≥ 10 on the AUDIT-C questionnaire
• abuse of or dependence on illegal drugs in the last 6 months revealed by the medical history
• regular use of tobacco products other than cigarettes
• current or previous (last 6 months) use of electronic cigarette
• pregnant women
• breastfeeding women
• protected adults
• current or past 3 months participation in another interventional research
• current or past (last 3 months) use of smoking cessation medication such as varenicline, bupropion, nicotine replacement therapies
• known lactose intolerance (placebo tablets contain lactose)
• hypersensitivity to the active substance or to any of the excipients
• known severe renal failure

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Groupe Hospitalier Pitié-Salpétrière

Paris, 75013, France

Location

Related Publications (1)

• Berlin I, Dautzenberg B, Lehmann B, Palmyre J, Liegey E, De Rycke Y, Tubach F. Randomised, placebo-controlled, double-blind, double-dummy, multicentre trial comparing electronic cigarettes with nicotine to varenicline and to electronic cigarettes without nicotine: the ECSMOKE trial protocol. BMJ Open. 2019 May 24;9(5):e028832. doi: 10.1136/bmjopen-2018-028832.

  PMID: 31129603 DERIVED

MeSH Terms

Conditions

Smoking Cessation; Cigarette Smoking; Vaping

Interventions

Electronic Nicotine Delivery Systems; Nicotine; Varenicline

Condition Hierarchy (Ancestors)

Health Behavior; Behavior; Tobacco Smoking; Smoking; Tobacco Use

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quinoxalines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo and reference treatment controlled, multicenter, double blind, double dummy, parallel group, pivotal, phase III trial.

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 15, 2018
• Study Start: October 17, 2018
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: December 29, 2025

Record last verified: 2025-12

Locations

FR (1)