A Randomized, Placebo Controlled, Double Blind, Double Dummy, Multicenter Trial Comparing Electronic Cigarettes With Nicotine to Varenicline and to Electronic Cigarettes Without Nicotine.
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 650
- 试验地点
- 1
- 主要终点
- Continuous smoking abstinence rate
研究概览
简要总结
Background:
Electronic cigarettes (EC) mainly containing nicotine (88-95 % of users) are widely and growingly used worldwide. It is estimated that there were 1.7 million daily users in France in 2016. Although the number of publications about its use is increasing exponentially, there are no evidence based, unbiased, head-to-head comparison data about its efficacy as an aid to smoking cessation. As of today, only two head-to-head randomized studies have been published, both reported negative results at the main endpoint but they used first and second generation EC delivering nicotine with low or unknown bioavailability. Recent EC deliver nicotine with largely improved bioavailability.
One of the randomized studies compared EC with and without nicotine to nicotine patch and reported similar smoking cessation rate at main outcome. However, there is no published, double blind study comparing EC use with a well-studied, licensed smoking cessation medication.
Superiority of EC with nicotine compared to EC without nicotine and to a reference smoking cessation medication while collecting also straightforward information about safety, would allow proposing EC with nicotine to the large population of smokers who intend to quit and situate it among the approved smoking cessation treatments.
The clinical study's hypothesis:
EC containing nicotine can be considered as a nicotine replacement therapy having, probably, a better bioavailability of nicotine than the marketed pharmaceutical NRTs, first line medications of smoking cessation. It is therefore of interest to compare EC containing nicotine to EC without nicotine but also to a reference medication with demonstrated efficacy in smoking cessation. We hypothesize that EC with nicotine provides a higher smoking abstinence rate than EC without nicotine and may be as good as varenicline, our reference medication.
详细描述
This is a randomized, placebo controlled, multicenter, double dummy, parallel groups, phase III type pivotal trial.
Included participants are randomly assigned to one of the 3 groups:
A) Control group: Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline: placebo condition B) Experimental group: Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline: ECwN condition C) Reference group: ECwoN plus varenicline tablets: varenicline condition Ratio: A:B:C= 1:3:3 Each participant uses an EC and 2x2 tablets per day. Group allocation is stratified by age at cut off of 45 years.
Enrolment is initiated by two ways:
• Potential participants aware of the study register at the study's recruitment website; call in or send an email followed by a phone screen. The screening starts with the participant's information about the study's aims, constraints, benefits and risks. A maximum one week delay of reflection is allowed if the potential participant is asking for a delay to sign his/her consent form.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double Blind
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Smokers smoking at least 10 cigarettes/day (factory made or roll-your-own) in the past year
- •Aged 18 to 70 years
- •Motivated to quit defined as a score > 5 on a visual rating scale ranging from 0 (not motivated at all) to 10 (extremely motivated)
- •Signed written informed consent
- •Understanding and speaking French
- •Women of childbearing age can be included if they use an effective contraceptive method: either hormonal contraception or an intrauterine device started at least one month before the first research visit
- •Individual affiliated to a health insurance system as defined by the sponsor (except Aide Médicale d'État =AME)
- •Previous failure of nicotine replacement therapy for smoking cessation
排除标准
- •any unstable disease condition within the last 3 months defined by the investigator as major change in symptoms or treatments such as 1.1.recent myocardial infarction, 1.2.unstable or worsening angina 1.3.severe cardiac arrhythmia 1.4.unstable or uncontrolled arterial hypertension 1.5.recent stroke 1.6.cerebrovascular disease 1.7.obliterative peripheral arterial disease 1.8.cardiac insufficiency 1.9.diabetes 1.10.hyperthyroidism 1.11.pheochromocytoma 1.12.severe hepatic insufficiency 1.13.history of seizures 1.14.severe depression 1.15.chronic obstructive pulmonary disease (COPD)
- •any life threatening condition with life-expectancy of less than 3 months
- •alcohol use disorder defined as a score ≥ 10 on the AUDIT-C questionnaire
- •abuse of or dependence on illegal drugs in the last 6 months revealed by the medical history
- •regular use of tobacco products other than cigarettes
- •current or previous (last 6 months) use of electronic cigarette
- •pregnant women
- •breastfeeding women
- •protected adults
- •current or past 3 months participation in another interventional research
- •current or past (last 3 months) use of smoking cessation medication such as varenicline, bupropion, nicotine replacement therapies
- •known lactose intolerance (placebo tablets contain lactose)
- •hypersensitivity to the active substance or to any of the excipients
- •known severe renal failure
研究组 & 干预措施
Electronic cigarette condition
Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline
干预措施: Electronic cigarette with nicotine (ECwN) plus placebo tablets of varenicline (Drug)
Varenicline condition
Reference group: Electronic cigarette without nicotine (ECwoN) plus active varenicline tablets
干预措施: Electronic cigarette without nicotine (ECwN) plus active varenicline tablets (Drug)
Placebo condition
Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline
干预措施: Electronic cigarette without nicotine (ECwoN) plus placebo tablets of varenicline (Drug)
结局指标
主要结局
Continuous smoking abstinence rate
时间窗: Weeks 9 to 12
Abstinence from conventional/combustible cigarettes during the last 4 weeks (weeks 9 to 12) of the treatment period of 3 months defined at Visit 4 AND Visit 5 as self-report of no smoking during the previous 2 weeks confirmed by expired air CO ≤ 8 ppm.
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]).(From randomisation up to end of study (Week 24 after target quit date).)
- Point prevalence abstinence rate: 7-day smoking abstinence at each visit.(From randomisation up to end of study (Week 24 after target quit date).)
- Time to relapse to smoking after the predefined quit day.(From randomisation up to end of study (Week 24 after target quit date).)
- Change in cigarettes/day consumption(From randomisation up to end of study (Week 24 after target quit date).)
- French Tobacco Craving Questionnaire of 12 items (FTCQ-12)(From randomisation up to end of study (Week 24 after target quit date).)
- Minnesota Nicotine Withdrawal Scale(From randomisation up to end of study (Week 24 after target quit date).)