Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial | BMC Public Health

Study population

People who live in NZ and smoke tobacco every day.

Eligibility criteria

Eligible participants are those aged ≥ 18 years, motivated to quit smoking within the next two weeks, 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 smartphone. Participants must also be willing to use either of the intervention products to help quit smoking.

Pregnant or breastfeeding women or women who are trying to become pregnant in the next three months will be excluded, as will be people currently using smoking cessation medication (including daily use of an e-cigarette in the last month), enrolled in another cessation programme or trial, or with known hypersensitivity to cytisine or nicotine e-cigarettes. Participants will be excluded if they have a strong preference to use or not use either product in their quit attempt or who have another member of their household already enrolled in the study. Participants will also be excluded if they 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) or have a history of seizures. These exclusion criteria are based on the product insert for cytisine and are precautionary (evidence to support these exclusions is absent or limited) [11].

Recruitment

Recruitment will be undertaken nationally using multi-media advertising, with targeted promotion to reach Māori, Pasifika and low socio-economic groups given their disproportionately higher smoking prevalence [1]. Participation in the trial will also be promoted via the national Quitline and community-based smoking cessation providers and general practitioners (GP).

Advertisements will direct potential participants to a study website where they can read the participant information sheet. A two-step-consent process will be used. First, interested participants will be asked for online consent to complete an online screening questionnaire to determine their eligibility for the trial and verify their contact details. Second, eligible and interested participants must provide online consent to enter the trial.

Baseline data will be collected via the online platform. Participants will then be asked to click the ‘randomisation’ button, whereupon they will be immediately randomised, informed of their allocated intervention, and automatically emailed a copy of the consent form and participant information sheet for their records. Their usual GP will also be automatically notified that their patient is enrolled in the trial.

Randomisation, allocation concealment and sequence generation

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

Blinding

This is a single-blind trial—participants will be aware of the intervention to which they have been allocated, and data collection by the trial research assistants includes questions specific to participants’ use of their allocated treatment. Except for the trial statistician (VP), the trial steering committee members will be blinded to treatment allocation until analyses are complete. If one or more of the study’s registered medical practitioners, or the study pharmacist, requires more details about a serious AE that requires unblinding, then they may request that the event be assessed by members of the trial’s independent Data Safety Monitoring Committee (DSMC), who will be unblinded by the project manager for the event.

Study interventions

Participants will be randomised to one of three treatments: 1) a nicotine e-cigarette, 2) cytisine, or 3) a nicotine e-cigarette plus cytisine, for 12 weeks. Trial products will be couriered to participants immediately after randomisation (signature required for receipt). The courier pack includes information on how to use the allocated product(s), a copy of the participant information sheet and consent form, a wallet card summarising how to use the allocated treatment, what participants should do if they experience any adverse health events, and contact details for key members of the study team. The courier company will automatically notify the study centre once the courier pack has been delivered, which will trigger the scheduling of the ‘quit date’ follow-up call and the start of the TBS programme.

Participants will be advised to begin their treatment the day after they receive their courier pack. They will be asked to reduce their smoking ad libitum over the first four days of treatment. The fifth day of treatment will be the participants designated ‘quit date’. Participants will be called on their quit date to verify they quit on that day and to collect outcome data. If a participant states that they have not quit on the scheduled ‘quit date’, they will be given one chance to reset their quit date (to within the next seven days), with this date becoming their new ‘quit date’ (which triggers the scheduling of all subsequent follow-up calls). For participants who cannot be contacted, their ‘quit date’ will be set in the system as six days after receiving their courier pack. Participants will be told that even if they lapse back to smoking, they should continue using the treatment they have been allocated. Throughout the trial, participants will be free to take whatever medications they wish, except for those noted under the exclusion criteria above.

Treatment group (cytisine only):

Participants allocated cytisine will be instructed to follow the manufacturer’s 25-day dosing regimen [11]:

• days 1–3: one tablet (1.5 mg) every two hours through the waking day (six tablets/day)

• days 4–12: one tablet every 2.5 h (five tablets/day)

• days 13–16: one tablet every three hours (four tablets/day)

• days 17–20: one tablet every 4–5 h (three tablets/day)

• days 21–25: one tablet every six hours (two tablets/day)

In addition, between day 26 and the end of week 12, participants will be advised to take a maintenance dose of one cytisine tablet every six hours (two tablets/day), to match the treatment duration used in a previous NZ cytisine vs varenicline non-inferiority trial [9].

Treatment group (nicotine e-cigarette only)

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 is the ‘UpOX’ closed pod system containing 3% nicotine salt (30 mg/mL). A tobacco flavour e-liquid will be provided as this is the most common flavour chosen by people who smoke when transitioning away from tobacco onto vapes. Participants will be advised that they should try and use only the product provided, but if they find that the nicotine strength is not sufficiently addressing their cravings (or the flavour is unpleasant) they may try alternative nicotine strengths or flavours—but at their own cost. The nicotine e-liquid supplied will be independently assessed by LabTech Scientific and Technical Services, Auckland, NZ, to verify the nicotine content is as labelled.

Treatment group (cytisine plus nicotine e-cigarette)

Participants allocated cytisine plus the e-cigarette will be instructed to follow the manufacturer’s instructions for use, as above.

Behavioural support (all groups)

All participants will receive the STOMP programme [24], an evidence-based text message smoking cessation advice, support, distraction and motivation programme to support individuals to quit smoking and maintain cessation. The programme includes two-way functionality to support individuals during cravings, is personally tailored, and 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). Text messages can be received even if the phone has no credit. Participants can opt-out of the service at any time by free texting back ‘STOP QUIT’.