Efficacy and Safety of E-cigarettes for Smoking Cessation in Middle-aged Heavy Smokers

Study Overview
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Brief Summary
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Abstract Rationale. Electronic cigarette use is increasing at an exponential rate in Finland and internationally. The health consequences of vaporised aerosols in electronic cigarettes are largely unknown especially in a long run. Still, very few studies are available on quitting attempts with e-cigarettes as a smoking cessation tool compared to evidence based cessation pharmacotherapy in adult smokers who want to quit. Research Objective: To investigate effectiveness and safety of e-cigarettes for smoking cessation in middle-aged smokers, and to compare the effectiveness of them to varenicline. Our study provides new information of success in smoking cessation among heavy adult smokers for clinicians. Design: A double-blind, randomised, placebo-controlled clinical trial with the intervention phase of 12 weeks and the observational phase up to 52 weeks. This is an investigator initiated study. Setting: Volunteer middle-aged daily smokers, who were recruited through newspaper announcements. Some of the cohort subjects were re-recruited from our previous follow-up study as many of them continued daily smoking during the whole follow-up period. Participants: Targeted sample size of 450 adult heavy smokers, who want to quit smoking and are willing to participate up to 52 weeks´ follow-up. Intervention and procedures: Standardized self-reported questionnaires with detailed smoking history with assessment of motivation to quit smoking, parameters of nicotine dependence, symptoms will be included. Smoking status will be repeatedly reassessed during the study visits, and self-reported smoking abstinence is verified with exhaled-carbon monoxide (CO) assessment. All adverse side effects either of drugs or of e-cigarettes, and symptoms related to the drugs or to withdrawal from smoking will be carefully reported.

Detailed Description
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This is a study with three arms. Each arm has 12 weeks intervention and observation up to 12 months: A.Nicotine containing e-cigarettes + placebo-pills + Motivational Interview (MI) Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml /month refill containing 18mg/ml nicotine with cigarette taste for 12 weeks. Participants are allowed to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day during the 2nd follow-up week Placebo -pills: starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on days 4.-5.Continuing weeks: 1mg twice daily up to 12 weeks B.Nicotine-free e-cigarettes + varenicline + MI Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml /month refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are allowed to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day during the 2nd follow-up week Varenicline (Chantix®) Starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on days 4.-5. Continuing weeks: 1mg twice daily up to 12 weeks C.Placebo-varenicline + nicotine -free e-cigarettes + MI Placebo -pills : starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on days 4.-5.Continuing weeks: 1mg twice daily up to 12 weeks Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ 6x 10ml /month refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are allowed to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day during the 2nd follow-up week

Official Title
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Efficacy and Safety of E-cigarettes for Smoking Cessation in Middle-aged Heavy Smokers

Conditions
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Smoking Cessation, Electronic Cigarette

Intervention / Treatment
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* Drug: Nicotine
* Drug: Varenicline Tartrate
* Behavioral: Motivational Interview


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 25 to under 75 years Has smoked over 10 years on a daily basis and being a current smoker with at least 10 cig/day for at least past 5 years Good general health Intent to quit smoking Exhaled carbon monoxide level at least 15ppm at the baseline visit Strong nicotine dependence defined by Fagerström Test for Nicotine Dependence (FTND) ≥ 5 and by Heaviness of Smoking Index (HSI) ≥3 intent to quit smoking prepared to follow the trial protocol and able to provide written consent. Exclusion Criteria: Pregnancy or gestation or intend to get pregnant during the study follow-up Use of smoking cessation pharmacotherapy or ECs during the past year Attempt of smoking cessation by using of e-cigarettes during the past year Any cancer (at least five healthy follow-up years after stopping the cancer therapy) Instable (ischemic) vascular or heart disease Recent myocardial infarction in the past three months High blood pressure (systolic BP> 140mmHg or diastolic 90mmHg at rest) History of major psychiatric depression or other psychiatric conditions and daily use of any psychiatric medicine Current addiction of alcohol or misuse of substance Inability to express himself/herself Known allergy to any of the study medications Severe allergy or poorly controlled asthma or other pulmonary disease Epilepsy

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotine containing e-cigarettes<br>Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI) | Drug: Nicotine<br>* Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI)<br>* Other names: Innokin Endura T20S;|
| Active Comparator: Nicotine-free e-cigarettes<br>Nicotine-free e-cigarettes + varenicline tartrate+ MI | Drug: Varenicline Tartrate<br>* Varenicline + Innokin Endura T20S electronic inhaler but without any nicotine content + MI<br>* Other names: Champix;|
| Placebo Comparator: Motivational Interview (MI)<br>Placebo-varenicline + nicotine -free e-cigarettes + MI | Behavioral: Motivational Interview<br>* Placebo-varenicline + Innokin ENdura T20S electronic inhaler but without any nicotine content +MI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking cessation during the follow-up visit at week 26 | 7-day point prevalence verified by exhaled-CO<10ppm | 24 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Smoking cessation at any other study visit | 7-day point prevalence verified by exhaled-CO < 10pp | Baseline,1, 12 and 52 week | 
| Reduce smoking at any study visit | Prevalence of those who succeeded to decrease the number of daily cigarettes during the study | Baseline, 1,4 ,12,16, 26, 36 and 52 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking Cessation, Electronic cigarette, Adults