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

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

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Other: ENDS (vaporizer/e-cig) and smoking cessation counseling; Other: Smoking cessation counseling

• Study Type: Interventional
• Enrollment (Actual): 1246
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • University Clinic for General Internal Medicine, Bern University Hospital
  • Geneva, Switzerland, 1211
    • Département de médecine interne, Hôpitaux universitaires de Genève
  • Saint-Gall, Switzerland
    • Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen
  • Zürich, Switzerland
    • Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Unisanté, Centre universitaire de médecine générale et santé publique, Université de Lausanne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control group	Other: Smoking cessation counseling; 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.
EXPERIMENTAL: Intervention group	Other: ENDS (vaporizer/e-cig) and smoking cessation counseling; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: University of Zurich; Swiss National Science Foundation; University of Lausanne; University of Geneva, Switzerland; State Hospital, St. Gallen

Publications and helpful links

General Publications

• Bullen C, Howe C, Laugesen M, McRobbie H, Parag V, Williman J, Walker N. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013 Nov 16;382(9905):1629-37. doi: 10.1016/S0140-6736(13)61842-5. Epub 2013 Sep 9.
• Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014 Apr;5(2):67-86. doi: 10.1177/2042098614524430.
• Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991 Sep;86(9):1119-27. doi: 10.1111/j.1360-0443.1991.tb01879.x.
• Caponnetto P, Campagna D, Cibella F, Morjaria JB, Caruso M, Russo C, Polosa R. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013 Jun 24;8(6):e66317. doi: 10.1371/journal.pone.0066317. Print 2013. Erratum In: PLoS One. 2014;9(1). doi:10.1371/annotation/e12c22d3-a42b-455d-9100-6c7ee45d58d0.
• Hartmann-Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2016 Sep 14;9(9):CD010216. doi: 10.1002/14651858.CD010216.pub3.
• Malas M, van der Tempel J, Schwartz R, Minichiello A, Lightfoot C, Noormohamed A, Andrews J, Zawertailo L, Ferrence R. Electronic Cigarettes for Smoking Cessation: A Systematic Review. Nicotine Tob Res. 2016 Oct;18(10):1926-1936. doi: 10.1093/ntr/ntw119. Epub 2016 Apr 25.
• Nyilas S, Bauman G, Korten I, Pusterla O, Singer F, Ith M, Groen C, Schoeni A, Heverhagen JT, Christe A, Rodondi N, Bieri O, Geiser T, Auer R, Funke-Chambour M, Ebner L. MRI Shows Lung Perfusion Changes after Vaping and Smoking. Radiology. 2022 Jul;304(1):195-204. doi: 10.1148/radiol.211327. Epub 2022 Apr 5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 16, 2018
• Primary Completion (ACTUAL): April 30, 2022
• Study Completion (ACTUAL): April 30, 2022

Study Registration Dates

• First Submitted: June 19, 2018
• First Submitted That Met QC Criteria: July 5, 2018
• First Posted (ACTUAL): July 18, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 2017-02332

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No