The ESTxENDS Trial- Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cigarette) as an Aid for Smoking Cessation.

Study Overview
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Brief Summary
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Cigarette smoking is the leading cause of preventable death in Switzerland and still more than a quarter of the Swiss population smokes cigarettes. Recently, electronic nicotine delivery systems (ENDS; also called vaporizer or electronic cigarette) have become popular with smokers who want to stop smoking or reduce their exposure to inhaled chemicals since ENDS use appears to be safer than tobacco smoking. Only two rigorous randomized controlled trials (RCTs) on the efficacy of ENDS to help smokers quit have been published so far. They have promising, yet inconclusive results, as the number of included participants were small. The safety and potential adverse effects of ENDS are also largely unknown. While the aerosol the users inhale appears safe in laboratory conditions, the difference in exposure to chemicals (such as reduction in exposure to volatile organic compounds) and effects of chemicals on the body (adverse events, improved health-related outcomes and measures of oxidative stress) between smokers who quit (with or without ENDS) and those who use ENDS for a long time have not yet been assessed in an RCT. This study will therefore test the efficacy of ENDS for cigarette smoking cessation, the safety of ENDS on adverse events and the effect of ENDS on health-related outcomes and exposure to inhaled chemicals. The primary hypothesis of this trial is that providing cigarette smokers willing to quit smoking tobacco cigarettes with ENDS leads to a higher rate of smokers who quit cigarette smoking than only smoking cessation counseling with nicotine replacement therapy (NRT), which represents nowadays the standard of care. For this trial, cigarette smokers motivated to quit smoking cigarettes will be included. Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants in the control group will receive smoking cessation counseling only. Participants in both groups will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 6-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date and again at week 1, 2, 4 and 8 after the target quit date. After 6 months, participants will be asked to come to a final clinical visit.

Official Title
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Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (The ESTxENDS Trial)

Conditions
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Smoking Cessation

Intervention / Treatment
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* Other: ENDS (vaporizer/e-cig) and smoking cessation counseling
* Other: Smoking cessation counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Persons aged 18 or older Currently smoking 5 or more cigarettes a day for at least 12 months Willing to try to quit smoking within the next 3 months, Persons providing a valid phone number, a valid email address and/or a valid postal address. Exclusion Criteria: Known hypersensitivity or allergy to contents of the e-liquid Participation in another study with investigational drug within the 30 days preceding the baseline visit and during the present study where interactions are to be expected Women who are pregnant or breast feeding Intention to become pregnant during the course of the scheduled study intervention, i.e. within the first 6-months of the study Persons having used ENDS regularly in the 3 months preceding the baseline visit Persons having used nicotine replacement therapy (NRT) or other medications with demonstrated efficacy as an aid for smoking cessation such as varenicline or bupropion within the 3 months preceding the baseline visit Persons who cannot attend the 6- month follow-up visit for any reason Cannot understand instructions delivered in person or by phone, or otherwise unable to participate in study procedures

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br> | Other: ENDS (vaporizer/e-cig) and smoking cessation counseling<br>* Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 6-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6 months, participants will be asked to come to a final clinical visit.<br>|
| Active Comparator: Control group<br> | Other: Smoking cessation counseling<br>* Participants in the control group will receive smoking cessation counseling only. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 6-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6 months, participants will be asked to come to a final clinical visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous smoking abstinence (1) | Self-report of having smoked no cigarettes from quit date, validated by urinary levels of anabasine. If anabasine is missing, validation by exhaled carbon monoxide (CO). | 6 months post quit date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous smoking abstinence (2) | Self-report of having smoked no cigarettes from quit date, validated by urinary levels of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled carbon monoxide (CO). | 6 months post quit date | 
| Self-reported smoking abstinence allowing a 2-week'grace period' | Smoking abstinence allowing a 2-week'grace period' after the target quit date. | 4, 8 weeks and 6 months post quit date | 
| Validated smoking abstinence allowing a 2-week'grace period' (1) | Smoking abstinence allowing a 2-week'grace period' after the target quit date, validated by urinary levels of anabasine. If anabasine is missing validation by exhaled carbon monoxide (CO). | 6 months post quit date | 
| Validated smoking abstinence allowing a 2-week'grace period' (2) | Smoking abstinence allowing a 2-week'grace period' after the target quit date, validated by urinary levels of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled carbon monoxide (CO). | 6 months post quit date | 
| Self-reported smoking abstinence allowing up to 5 cigarettes | Smoking abstinence allowing up to 5 cigarettes in total after the target quit date. | 1, 2, 4, 8 weeks and 6 months post quit date | 
| Validated smoking abstinence allowing up to 5 cigarettes (1) | Smoking abstinence allowing up to 5 cigarettes in total after the target quit date, validated by urinary levels of anabasine. If anabasine is missing validation by exhaled carbon monoxide (CO). | 6 months post quit date | 
| Validated smoking abstinence allowing up to 5 cigarettes (2) | Smoking abstinence allowing up to 5 cigarettes in total after the target quit date, validated by urinary levels of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled carbon monoxide (CO). | 6 months post quit date | 
| Self-reported 7-day point prevalence abstinence | Self-report of having smoked no cigarettes in the past seven days. | 1, 2, 4, 8 weeks and 6 months post quit date | 
| Validated 7-day point prevalence abstinence (1) | Confirmation of having smoked no cigarettes in the past seven days, validated by urinary levels of anabasine. If anabasine is missing validation by exhaled carbon monoxide (CO). | 6 months post quit date | 
| Validated 7-day point prevalence abstinence (2) | Confirmation of having smoked no cigarettes in the past seven days, validated by urinary levels of NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol). If NNAL is missing, validation by urinary levels of anabasine or exhaled carbon monoxide (CO). | 6 months post quit date | 
| Number of cigarettes smoked per day (CPD) | self-reported | baseline, target quit date, 1, 2, 4, 8 weeks and 6 months post quit date | 
| Change in number of cigarettes smoked per day (CPD) | self-reported. Successful reduction defined as 50% reduction in CPD. | baseline, 6 months post quit date | 
| Use of any other smoking cessation products (NRT, Nicotine replacement therapy) | self-reported on whether and how often they used any NRT. | 1, 2, 4, 8 weeks and 6 months post quit date | 
| Withdrawal | The physical signs and symptoms associated with withdrawal, measured using the Minnesota Tobacco Withdrawal Scale (http://www.med.uvm.edu/behaviorandhealth/minnwsdefault). The Minnesota Tobacco Withdrawal Scale measures self-reported severity of nicotine withdrawal. The measure has 15 items, with five possible responses (0-5), thus scores on the scale range from 0 to 60. | baseline and 6 months post quit date | 
| Nicotine dependence | Nicotine dependence measured using the Fagerström Test. The Fagerström Test for Nicotine Dependence (FTND, Heatherton TF et al., 1991) is a standard instrument for assessing the intensity of physical addiction to nicotine. It contains six items that evaluate the quantity of cigarette consumption, the compulsion to use, and dependence. Two items have four possible responses (0-3) and four items have two possible responses (0-1). The nicotine dependence score ranges from 0 to 10. A score between 0 and 2 is considered as a low nicotine dependence, a score between 3 to 5 is considered as a medium nicotine dependence, a score between 6 and 7 is considered as a high nicotine dependence and a score between 8 and 10 is considered as a very high nicotine dependence. | baseline and 6 months post quit date | 
| Health-related quality of life | Measured using the Swiss EQ-5D. The EQ-5D questionnaire is a standardized measure of health status developed by the EuroQol Group (https://euroqol.org/). EQ-5D questionnaires have five dimensions: Mobility, Self-care, Usual Activities, Pain / Discomfort, Anxiety / Depression and all dimensions are described by five problem levels corresponding to participant response choices. | baseline and 6 months post quit date | 
| Use of any ENDS | self-reported on whether and how often they used any ENDS | 1, 2, 4, 8 weeks and 6 months post quit date | 
| Report on most common adverse events using ENDS | Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of ENDS, whether or not it is considered related to the product. | 1, 2, 4, 8 weeks and 6 months post quit date |