The ESTxENDS Trial- Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation-extension of Follow-up

Smoking Cessation Clinical Trial

— ESTxENDS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04236791
• Other study ID #: 2017-02332_2
• Status: Completed
• Phase: N/A
• Start date: July 16, 2018
• Est. completion date: August 31, 2023

Study information

• Verified date: September 2023
• Source: University of Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 24-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 6,12 and 24 months, participants will be asked to come to a clinical visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1246
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

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 24-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, 12 and 24 months, participants will be asked to come to a clinical visit.
• 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 24-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, 12 and 24 months, participants will be asked to come to a clinical visit.

Locations

Country	Name	City	State
Switzerland	University Clinic for General Internal Medicine, Bern University Hospital	Bern
Switzerland	Département de médecine interne, Hôpitaux universitaires de Genève	Geneva
Switzerland	Policlinique Médicale Universitaire, Université de Lausanne	Lausanne	Vaud
Switzerland	Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen	Saint-Gall
Switzerland	Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich	Zürich

Sponsors (8)

Lead Sponsor	Collaborator
University of Bern	Federal Office of Public Health, Switzerland, Krebsforschung Schweiz, Bern, Switzerland, State Hospital, St. Gallen, Swiss National Science Foundation, University of Geneva, Switzerland, University of Lausanne, University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	12 months post quit date
Primary	Validated 7-day point prevalence abstinence (1.1)	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).	24 months post quit date
Primary	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).	12 months post quit date
Primary	Validated 7-day point prevalence abstinence (2.1)	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).	24 months post quit date
Secondary	Self-reported 7-day point prevalence abstinence	Self-report of having smoked no cigarettes in the past seven days.	12, 24 months post quit date
Secondary	Continuous smoking abstinence	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).	12, 24 months post quit date
Secondary	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).	12, 24 months post quit date
Secondary	Self-reported smoking abstinence allowing a 2-week'grace period'	Smoking abstinence allowing a 2-week'grace period' after the target quit date.	12, 24 months post quit date
Secondary	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).	12, 24 months post quit date
Secondary	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).	12, 24 months post quit date
Secondary	Self-reported smoking abstinence allowing up to 5 cigarettes	Smoking abstinence allowing up to 5 cigarettes in total after the target quit date.	12, 24 months post quit date
Secondary	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).	12, 24 months post quit date
Secondary	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).	12, 24 months post quit date
Secondary	Number of cigarettes smoked per day (CPD)	self-reported	12, 24 months post quit date
Secondary	Change in number of cigarettes smoked per day (CPD)	self-reported.Successful reduction defined as 50% reduction in CPD.	12, 24 months post quit date
Secondary	Use of any other smoking cessation products (NRT, Nicotine replacement therapy)	self-reported on whether and how often they used any NRT.	12, 24 months post quit date
Secondary	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.	12, 24 months post quit date
Secondary	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.	12, 24 months post quit date
Secondary	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.	12, 24 months post quit date
Secondary	Use of any ENDS	self-reported on whether and how often they used any ENDS	12, 24 months post quit date
Secondary	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.	12, 24 months post quit date