Clinical trial NCT02417467: Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation (E3) Trial
Official title: Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation (E3) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smoking Cessation
Keywords: Electronic cigarette
E-cigarette
Smoking cessation
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: Sir Mortimer B. Davis - Jewish General Hospital
First posted: 2015-04-15
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Smoking-related diseases contribute to the death of more than 37,000 Canadians annually. Of that number, almost one-third die of cardiovascular-related causes. Smoking cessation can decrease the additional risk of heart disease by 50% after 1 year. However, even using smoking cessation therapies, only 10-20% of smokers will be able to successfully quit smoking long-term. Therefore, new and alternative treatments are needed.

The e-cigarette is a battery-powered device approximately the size and shape of a cigarette that creates a smoke-free vapour which is inhaled by the user. Since it feels like smoking a cigarette, using the e-cigarette may help some smokers quit. Some e-cigarettes also contain nicotine, which can reduce withdrawal symptoms from quitting smoking. However, e-cigarettes have not been approved for use for smoking cessation by Health Canada or the FDA. Despite this, these devices are rising in popularity. A recent US Centers for Disease Control survey found that of smokers who were motivated to quit within the next 6 months, 48.5% had tried e-cigarettes.

The Evaluating the Efficacy of E-Cigarette Use for Smoking Cessation (E3) Trial will be the first large trial to address the important issue of e-cigarettes for smoking cessation in Canada. The trial will randomly assign participants to receive nicotine e-cigarettes and minimal counseling, non-nicotine e-cigarettes and minimal counseling, or only minimal counseling for 12 weeks. Participants will then be followed for one year to see which (if any) group is more likely to have quit or reduced their smoking. Information about potential side effects and safety will also be collected. The E3 Trial will provide law-makers and the public with important information about the use of e-cigarettes for smoking cessation.

Detailed description: I. OVERALL STUDY OBJECTIVE The Evaluating the Efficacy of E-Cigarette use for Smoking Cessation (E3) Trial is a 5-year, multi-centre, randomized controlled trial (RCT) that seeks to assess the efficacy, safety, and tolerability of nicotine and non-nicotine electronic cigarettes (e-cigarettes) for smoking cessation in the general population.

II. SPECIFIC OBJECTIVES

1. To compare the efficacy of nicotine and non-nicotine e-cigarettes used with individual counselling for smoking cessation, to that of individual counselling alone, in terms of biochemically-validated 7-day point prevalence smoking abstinence at 52 weeks.
2. To examine the effect of nicotine and non-nicotine e-cigarettes on other measures of smoking reduction and cessation, including continuous abstinence and daily cigarette consumption at 4, 12, 24, and 52 weeks.
3. To describe the safety and tolerability of nicotine and non-nicotine e-cigarettes in terms of serious adverse events (SAEs), adverse events (AEs), drop-out rates due to side effects, and therapy adherence over the 12 week treatment period.

I. RATIONALE Smoking-related diseases contribute to the death of more than 37,000 Canadians annually. Of that number, almost one-third die of cardiovascular-related causes. Smoking cessation can decrease the additional risk of heart disease by 50% after one year of abstinence. However, even using traditional smoking cessation therapies, only 10-20% of smokers will be able to successfully quit smoking long-term. Therefore, new and alternative treatments are needed. The e-cigarette is a battery-powered device approximately the size and shape of a cigarette that creates a smoke-free vapour that is inhaled by the user, and is available in nicotine and non-nicotine varieties. Its mimicry of the act of smoking gives it the potential to target the habit-forming mechanism of smoking, and to mitigate withdrawal symptoms with nicotine replacement (in the case of nicotine e-cigarettes). However, e-cigarettes have not been approved for use for smoking cessation by Health Canada or the US Food and Drug Administration. Despite this, these devices are rising in popularity. A recent survey found that of smokers motivated to within 6 months, 48.5% had tried e-cigarettes. The E3 Trial will be the first conducted in the general population of Canadian smokers motivated to quit. It will also provide the longest-term (52 weeks) follow-up data on smoking reduction and cessation in smokers motivated to quit with the e-cigarette.

II. METHODS The investigators will conduct a multi-centre RCT with a treatment period of 12 weeks and follow-up of 52 weeks. A total of 486 participants will be randomized to one of three treatment arms: (1) nicotine e-cigarettes with individual counselling, (2) non-nicotine e-cigarettes with individual counselling, or (3) individual counselling alone. Eligible participants will be recruited from the general population, be at least 18 years of age, will self-identify as regular smokers (≥10 cigarettes per day for at least one year), and be motivated to quit. Participants will complete telephone follow-ups at weeks 1, 2, and 8. The participants will also return for clinic visits at weeks 4, 12, 24, and 52. Biochemically-validated smoking abstinence will be measured at all clinic visits using exhaled carbon monoxide. At follow-up calls and visits, the investigators will collect information about self-reported smoking, e-cigarette use, withdrawal symptoms, and side effects. The primary analysis will compare point-prevalence abstinence at 52 weeks between participants randomized to nicotine e-cigarettes versus individual counselling alone. Similar analyses will be conducted to compare abstinence across other trial arms. In secondary analyses, the investigators will examine point-prevalence abstinence at other follow-ups, as well as the effect of treatment group on continuous abstinence, daily cigarette consumption, and the occurrence of clinical events and side effects. A sample size of 486 was identified through power calculation, based on a 52-week point prevalence abstinence rate of 10% among participants randomized to counselling, with \>80% power to detect a ≥12% absolute difference in the prevalence of smoking abstinence at 52 weeks (e.g., a prevalence of abstinence in the nicotine e-cigarette group of 22%) with a two-tailed α of 0.05.

III. SIGNIFICANCE E-cigarettes are popular devices that may have the potential to facilitate smoking cessation. The E3 Trial will provide regulators, health care professionals, and smokers with important information about the efficacy and safety of e-cigarettes for smoking cessation.

IV. ADDENDUM The primary endpoint was changed from 52 weeks to 12 weeks following the early termination of enrollment (77% of target enrollment) due to a delay in product manufacturing.

Eligibility criteria: 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 females;
* Current or recent use (in the past 30 days) of any pharmacotherapy or behavioural 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 one 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.

Primary outcomes:
measure: Number of participants with 7-day point prevalence smoking abstinence
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of participants with 7-day point prevalence smoking abstinence
timeFrame: 4, 12, and 24 weeks
measure: Number of participants with continuous abstinence from smoking
timeFrame: 4, 12, 24, and 52 weeks
measure: Change in daily cigarette consumption
timeFrame: 1, 2, 4, 8, 12, 18, 24, and 52 weeks
measure: The frequency of serious adverse events
timeFrame: 12 weeks
measure: The frequency of adverse events
timeFrame: 12 weeks
measure: The frequency of drop-outs
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: Allen Greenspoon Medicine Profesionnal Corporation
state: Ontario
city: Kingston
country: Canada
facility: Baran Medicine Professional Corporation
state: Ontario
city: Ottawa
country: Canada
facility: Institut de recherche de l'Hôpital Montfort
state: Ontario
city: Ottawa
country: Canada
facility: The Bridge Engagement Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Thornhill
country: Canada
facility: Canadian Centre for Clinical Trials
state: Ontario
city: Toronto
country: Canada
facility: Michael Garron Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Laval
country: Canada
facility: Hôpital Cité-de-la-Santé
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Institut de cardiologie et de pneumologie de Québec (IUCPQ)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de recherche sur le vieillissement
state: Quebec
Study officials:
affiliation: McGill University, Jewish General Hospital
name: Mark J Eisenberg, MD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartmann-Boyce J, Theodoulou A, Farley A, Hajek P, Lycett D, Jones LL, Kudlek L, Heath L, Hajizadeh A, Schenkels M, Aveyard P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2021 Oct 6;10(10):CD006219. doi: 10.1002/14651858.CD006219.pub4.
citation: Eisenberg MJ, Hebert-Losier A, Windle SB, Greenspoon T, Brandys T, Fulop T, Nguyen T, Elkouri S, Montigny M, Wilderman I, Bertrand OF, Bostwick JA, Abrahamson J, Lacasse Y, Pakhale S, Cabaussel J, Filion KB; E3 Investigators. Effect of e-Cigarettes Plus Counseling vs Counseling Alone on Smoking Cessation: A Randomized Clinical Trial. JAMA. 2020 Nov 10;324(18):1844-1854. doi: 10.1001/jama.2020.18889.