Clinical trial NCT05311085: Cytisine and E-cigarettes With Supportive Text-messaging for Smoking Cessation (Cess@Tion)
Official title: Cytisine and E-cigarettes With Supportive Text-messaging for Smoking Cessation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smoking Cessation
Keywords: smoking cessation
e-cigarette
cytisine
vaping
pragmatic
effectiveness
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
First posted: 2022-04-05
Enrollment: 807
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research focuses on maximizing the benefits of proven smoking cessation interventions to support people who smoke to quit, as part of the strategy to help New Zealand become smoke-free. A large, pragmatic community-based clinical trial is planned which draws on 15 years of smoking cessation research undertaken by the study team. This research has shown that both cytisine and nicotine e-cigarettes are more effective than nicotine replacement therapy at helping people to quit smoking, and are more acceptable to users. New Zealand research has also shown that text-messages offering advice and support around quitting smoking are highly effective and acceptable. The planned trial will test whether using cytisine and nicotine e-cigarettes together will help more New Zealanders to quit smoking long-term, compared to using cytisine alone or nicotine e-cigarettes alone. Participants in all three groups will also receive smoking cessation text-messaging behavioral support.

Detailed description: Aim:

To evaluate the effectiveness, safety, and acceptability of combination treatment (cytisine plus nicotine e-cigarettes) compared to monotherapy (cytisine only or nicotine e-cigarettes only) on six-month smoking abstinence.

Trial design:

A single-blind, pragmatic three-arm, parallel group, pragmatic, community-based randomized trial.

Eligibility criteria:

Eligible participants must be daily smokers who live in New Zealand, are aged ≥18 years, and have no contraindications to the study treatment. Participants must be motivated to quit smoking within the next two weeks, be able to provide online consent, have daily access to a mobile telephone that can text and have access to the internet via a computer or smart phone. Participants must also be willing to use cytisine or an e-cigarette or both products to help quit smoking. Full details of inclusion and exclusion criteria are provided later in this trial registration.

Recruitment:

Participants will be recruited from throughout New Zealand using multi-media advertising, with targeted promotion to reach indigenous Māori, Pacific and low socio-economic groups given their disproportionately higher smoking prevalence. Advertisements will direct potential participants to a trial website where they can read the participant information sheet. A two step-consent process will be used. First, interested participants will be asked for on-line consent to complete an online screening questionnaire to determine their eligibility for the trial and verify their phone number. Second, eligible and interested participants will then provide online consent to enter the trial.

Baseline information:

Baseline data will then be collected via the online platform, and will include: demographic data, smoking history, cigarette dependence, motivation to quit, withdrawal symptoms and craving, cannabis use, alcohol use, self-reported comorbidities, concomitant medication, and health-related quality of life. Full details on the baseline data are provided later in this trial registration. The participant will then be asked to click the 'randomization' button, whereupon they will be immediately randomized and informed of their allocated intervention.

Randomization:

Participants will be assigned a unique registration number allocated by a central computer, following details submitted via the study website. Eligible participants will be randomized via computer (3:3:2 ratio) to one of three trial groups using stratified block randomization (block sizes of eight), and stratified by ethnicity (Māori, non-Māori). The randomization sequence will be generated by the trial statistician, and centrally managed and concealed until the point of randomization.

Blinding:

This is a single-blind trial as participants will be aware of the intervention to which they have been allocated, and data collection by the trial research assistants will include questions specific to use of participants allocated treatment. Except for the trial statistician, the trial steering committee members will remain blinded to treatment allocation until analyses are complete. The statistical analysis plan will be finalized and uploaded to the trial registry prior to the first participant being randomised.

Interventions:

Participants will be randomized to either 12 weeks of: 1) cytisine plus nicotine e-cigarette, 2) cytisine; or 3) nicotine e-cigarette. Participants allocated cytisine will be instructed to follow the manufacturer's 25-day dosing regimen. However, a maintenance dose of cytisine will be added for day 26 to week 12. Full details of the dosing regimen are provided later in this trial registration. Participants allocated a nicotine e-cigarette will be instructed to follow the manufacturer's instructions for use, with ad libitum use over 12 weeks. The e-cigarette device used in the trial will be the 'UpOX', a closed pod system with a 3% nicotine salt (30mg/mL). A tobacco flavour e-liquid will be provided as this is the usual flavour chosen by smokers when they are transitioning away from tobacco. Participants will be advised that they should try and use only the product provided, but if they are finding the nicotine strength is not sufficiently addressing their carvings (or the flavour is distasteful) they are free to try alternative nicotine strengths or flavours, but that this will be at their own cost). Participants will be asked at follow-up about any switching of products. Participants allocated both cytisine and a nicotine e-cigarette will be instructed to follow the manufacturer's instructions for use (as mentioned above). All participants will also receive a evidence-based, text-message behavioral support program. This theoretically-based text message program will provide smoking cessation advice and motivation to support individuals to quit smoking and maintain cessation. The program includes 2-way functionality to support individuals during cravings. Regular, text messages providing smoking cessation advice, tips to cope with cravings, advice on avoiding smoking triggers, and motivational support will be delivered over a six-month period (five messages a day for six weeks, then three per week until the end of the 26th week - i.e., six-month follow-up). All 12-weeks of trial products will be couriered to participants immediately after randomization, at no cost to participants. The courier company will notify the study center immediately after the courier pack has been delivered, which will trigger the scheduling of the 'quit date' (day 0) follow-up call and the start of the text message behavioural support program.

Follow-up:

Participants will be asked to begin their treatment the day after they receive their courier pack and to reduce their smoking ad libitum over the first four days of treatment so that they are not smoking at all by the fifth day ('quit date'). Participants will be called on their quit date to verify they are quitting on that day (and to collect outcome data). If a participant states that they are not quitting on the scheduled 'quit date', they will be given one chance to reset their quit date within the next seven days, with this date becoming their new 'quit date' (which will trigger the scheduling of all subsequent follow-up calls). For participants who are unable to be contacted at quit date, their 'quit date' will be set in the system as six days after they received their courier pack (which will trigger the scheduling of all subsequent follow-up calls). Participants will be advised to continue with their allocated treatment irrespective of any lapses back to smoking. Further follow-up calls will be made at one, three and six months after their quit date to collect outcome data. Approximately two thirds of participants will also be contacted 12 months after their quit date to collect outcome data.

Outcome data:

The primary outcome is six-month carbon-monoxide verified continuous abstinence from smoking (i.e. smoking ≤ five cigarettes since quit date). Outcomes collected at three, six, and 12 months post-quit date include other cessation outcomes, treatment use, acceptability, and adverse events. Full details on the outcome data are provided later in this trial registration.

Trial power:

A sample size of 800 (N=300 in the cytisine group, N=300 in the cytisine plus nicotine e-cigarette group, and N=200 in the nicotine e-cigarette group) will provide 90% power at two-sided p=0.05 to detect an absolute difference of 13% in six-month smoking abstinence rates between the combination treatment group and the cytisine group, and 16% difference between the combination treatment group and the nicotine e-cigarette group (taking account of multiple testing). The predicted difference is based on trial evidence for six month verified continuous abstinence quit rates of 9% for nicotine e-cigarettes, 12% for cytisine, and 25% for combination cessation treatment (averaged). The sample size accounts for a 28% loss-to-follow-up at six months.

Statistical analysis:

All statistical analyses will be performed using SAS version 9.4 (SAS Institute Inc. Cary NC), and R. Data analyses will be specified a priori in a statistical analysis plan prepared by the trial statistician and posted on the trial registry prior to the first participant recruitment. No interim analyses will be undertaken. All analyses will be conducted for the following comparisons, 1) cytisine plus nicotine e-cigarettes vs cytisine and 2) cytisine plus nicotine e-cigarettes vs nicotine e-cigarettes. The main analyses will be carried out on an intention-to-treat basis, with multiple imputation analysis performed to account for missing data using the fully conditional specification logistic regression method (data will be assumed to be missing at random).

Eligibility criteria: Inclusion Criteria:

* Daily smokers who live in New Zealand
* Aged ≥18 years
* Motivated to quit smoking within the next two weeks
* Able to provide consent
* Have daily access to a mobile telephone that can text
* Have access to the internet via a computer or smart phone
* Are willing to use cytisine or an e-cigarette or both products to help quit smoking

Exclusion Criteria:

* Have another person in their household currently enrolled in the study
* Are pregnant/breastfeeding, or are women trying to become pregnant in the next three months
* Are currently using smoking cessation medication (including using e-cigarettes daily for the last month)
* Are enrolled in another cessation programme/trial
* Have a known hypersensitivity to cytisine or nicotine e-cigarettes
* Self-report moderate/severe renal impairment
* Are undergoing treatment for active/latent tuberculosis
* Have experienced a myocardial infarction, stroke, or severe angina within the previous two weeks
* Have uncontrolled high blood pressure (\>150 mmHg systolic, \>100 mmHg diastolic)
* Have a history of seizures / epilepsy
* Have a strong preference to use or not to use cytisine and/or e-cigarettes in their quit attempt.
* Have a history of severe allergy and/or poorly controlled asthma.

Primary outcomes:
measure: Proportion of participants with verified continuous smoking abstinence
timeFrame: Six months post-quit date
Secondary outcomes:
measure: Age
timeFrame: Assessed at baseline
measure: Gender
timeFrame: Assessed at baseline
measure: Ethnicity (self-reported)
timeFrame: Assessed at baseline
measure: Education
timeFrame: Assessed at baseline
measure: Age started smoking
timeFrame: Assessed at baseline
measure: Number of years of continuous smoking
timeFrame: Assessed at baseline
measure: Type of cigarettes smoked
timeFrame: Assessed at baseline
measure: Number of cigarettes smoked per day
timeFrame: Assessed at baseline
measure: Mean pack size (Factory-made cigarettes)
timeFrame: Assessed at baseline
measure: Median pack size (Factory-made cigarettes)
timeFrame: Assessed at baseline
measure: Mean pouch size (Roll your-own tobacco)
timeFrame: Assessed at baseline
measure: Median pouch size (Roll your-own tobacco)
timeFrame: Assessed at baseline
measure: Time taken to smoke the contents of a pack or pouch
timeFrame: Assessed at baseline
measure: Level of cigarette dependence
timeFrame: Assessed at baseline
measure: At least one quit attempt in the past 12 months
timeFrame: Assessed at baseline
measure: Time quit, for last quit attempt
timeFrame: Assessed at baseline
measure: Methods used in previous quit attempt
timeFrame: Assessed at baseline
measure: Reduction in the number of cigarettes smoked in the past 12 months
timeFrame: Assessed at baseline
measure: Motivation to quit
timeFrame: Assessed at baseline
measure: Chances of giving up smoking
timeFrame: Assessed at baseline
measure: Living with other people who smoke tobacco
timeFrame: Assessed at baseline
measure: Living with other people who use nicotine e-cigarettes (vapes)
timeFrame: Assessed at baseline
measure: Has close friends who use nicotine e-cigarettes (vapes)
timeFrame: Assessed at baseline
measure: Alcohol use
timeFrame: Assessed at baseline
measure: Cannabis use
timeFrame: Assessed at baseline
measure: Self-reported continuous smoking abstinence
timeFrame: Assessed at one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Self-reported 7-day point prevalence smoking abstinence
timeFrame: Assessed at one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in the number of cigarettes smoked per day (if smoking) by participants
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Reduction in smoking by participants
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Time to first lapse back to smoking by participants
timeFrame: Assessed at one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Time to first relapse back to smoking by participants
timeFrame: Assessed at one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Proportion of participants who use other smoking cessation methods
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Health-related quality of life (five domains)
timeFrame: Assessed at baseline, three, six and 12 months post-quit date
measure: Health-related quality of life (self-rated health)
timeFrame: Assessed at baseline, three, six and 12 months post-quit date
measure: Participant compliance with cytisine use
timeFrame: Measured at three months post quit date.
measure: Number of cytisine tablets taken by participants
timeFrame: Measured at one and three months post quit date.
measure: Daily use of the allocated treatment by participants
timeFrame: Measured at quit date (day 0), then at one month post quit date.
measure: Reasons for not using allocated treatment
timeFrame: Measured at quit date (day 0), then at one month post quit date.
measure: Frequency of use of the e-cigarette, by participants allocated e-cigarettes
timeFrame: Measured at three months post quit date.
measure: Number of nicotine pods used, by participants allocated e-cigarettes
timeFrame: Measured at one and three months post quit date.
measure: Signs and symptoms of nicotine withdrawal in participants
timeFrame: Measured at baseline and at three months (end of treatment).
measure: Urge to smoke in participants
timeFrame: Measured at baseline and at three months (end of treatment).
measure: Treatment switching (crossover from cytisine-only to e-cigarette)
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Treatment switching (crossover from cytisine-only to e-cigarette): nicotine content of e-cigarette
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Treatment switching (crossover from e-cigarette-only to cytisine)
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Treatment switching (crossover from e-cigarette-only to cytisine): source of cytisine
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change in e-cigarette use
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Dual use of treatment and tobacco by participants
timeFrame: Assessed at one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Continuation of product use by participants
timeFrame: Measured at six (in all) and 12 months (in a subsample).
measure: Acceptability of allocated product
timeFrame: Measured at three months post-quit date (end of treatment)
measure: Participants recommendations regarding the allocated product
timeFrame: Measured at three months post-quit date (end of treatment)
measure: Number of participants with self-reported adverse events
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Number of self-reported adverse events
timeFrame: Assessed at quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in body mass index
timeFrame: Asked at three and six months post-quit date
measure: Change from baseline in frequency of shortness of breath in participants
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in frequency of coughing in participants
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in asthma severity, in those participants with asthma
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in severity of chronic pain, in those participants with chronic pain.
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in severity of Chronic Obstructive Pulmonary Disease (COPD), in those participants with COPD.
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Change from baseline in severity of mental health concerns, in those participants with mental health concerns.
timeFrame: Measured at three and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Concomitant medication
timeFrame: Assessed at baseline, quit date (day 0), then one, three, and six months post-quit date (and at 12 months post-quit date in a subsample)
measure: Mean number of text-based behavioral support messages received by participants
timeFrame: Assessed at six months
measure: Median number of text-based behavioral support messages received by participants
timeFrame: Assessed at six months
measure: Marginal cost per quitter
timeFrame: Assessed at six months
Other outcomes:
Locations:
city: Auckland
country: New Zealand
facility: National Institute for Health Innovation, School of Population Health, Faculty of Medical and Health Sciences, University of Auckland
Study officials:
affiliation: University of Auckland, New Zealand
name: Natalie Walker, PhD
role: PRINCIPAL_INVESTIGATOR
References: