Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an aid for smoking cessation: The ESTxENS multicentre randomized controlled trial
Description: This study is registered on the Swiss National Clinical Trials Portal (SNCTP) under the number SNCTP000002857 and on ClinicalTrials.gov with the identifier NCT03589989More information on the study can be found on the trial website: https://www.estxends.ch/Recruitment has been completed in June 2021 with 1243 randomized out of 1173 planned. Six-months follow-up completed in Spring 2023. Publication of results scheduled in Winter 2022-2023.Background: Cigarette smoking is the leading cause of preventable death in Switzerland. Recently, electronic nicotine delivery systems (ENDS or e-cigarettes) have become popular with smokers who want to switch from tobacco cigarettes to ENDS to reduce their exposure to toxic compounds or to stop smoking. Only two rigorous RCTs have been published so far. They have promising, yet inconclusive results, as they were based on small samples. 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 toxins (such as measures exposure to organic compounds) and effect of toxins on the body (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. Objectives: Test ENDS on: 1) the efficacy for cigarette smoking cessation and reducing the number of cigarettes smoked over 6 months of follow-up; 2) the safety of ENDS on adverse events; 3) the effect of ENDS on reducing exposure to inhaled toxic compounds; 4) the effect of ENDS on health-related outcomes (clinical outcomes: respiratory symptoms; surrogate outcomes: oxidative stress, risk factors for heart disease).Hypotheses: ENDS are a safe alternative to cigarette smoking. They help smokers quit smoking, reduce their exposure to toxic compounds released by tobacco cigarettes, and improve markers of oxidative stress and risk factors for heart disease and respiratory symptoms.Methods: We plan to include 1172 smokers in a pragmatic RCT that will add ENDS to smoking cessation counselling (SCC), and compare ENDS to SCC alone. Our main outcome will be continuous smoking cessation after target quit date at 6-month follow-up, with blinded assessment and biochemical verification by exhaled carbon monoxide (CO) and urinary anabasine levels. In intention to treat analyses, assuming a 5% lost to follow-up, we will have 90% power at two sided a of 5% of detecting a 7% absolute increase in smoking cessation rate (from 12% to 19%, RR 1.6, assuming ENDS are as efficacious as nicotine replacement therapy (NRTs) plus SSC. Participants in the intervention arm will receive free ENDS, nicotine-containing e-liquids ad libitum, and technical support for using ENDS. Participants in both arms will receive SCC in four sessions over two months over the phone, and be allowed to use NRTs and other smoking cessation help. In order to minimize attrition in the control group, we will provide members with the intervention after the 6-month follow-up visit. At baseline and 6-month follow-up, we will distribute questionnaires and perform a battery of clinical tests, including tests for cardiovascular risk factors (blood pressure, lipids, and glucose; body mass index), determine urinary biomarkers for tobacco-specific nitrosamines (TSNAs), nicotine metabolites (nicotine, cotinine, anabasine), NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol), metabolites of polycyclic aromatic hydrocarbons (PAHs) (1-hydroxypyrene, 1-and 2-naphthol) and oxidative stress markers in urine (8-hydroxy-2'-deoxyguanosine and 8-iso-prostaglandin F22a).Working group: This is a collaboration between clinicians expert both in conducting RCTs in smoking cessation and treating smokers in the community and experts in measuring pollutants and their effects in humans. Significance: Despite the wide use of ENDS, efficacy for smoking cessation and safety is uncertain and no published RCTs have evaluated the toxicity of ENDS. For objectivity, these outcomes should be assessed independently from the tobacco and ENDS industry. We will provide users, health care providers, and policy makers with evidence to support smoking cessation counselling, and shape ENDS regulation on the national and international level.
Amount: CHF 1,897,000
Funding type: research
Funder scheme: Investigator Initiated Clinical Trials (IICT)
Start date: 2017-06-01
End date: 2021-12-31
Investigator: Auer, Reto
Institution: University of Berne – BE
Funded outputs count: 18
Funder award ID: 173552
OpenAlex ID: G7578075670