Nicotine Patch Plus Nicotine Mouth Spray Versus Nicotine Reduction for Vaping Cessation

This research focuses on maximizing the chances of successfully quitting vaping. A large, pragmatic community-based clinical trial is planned in New Zealand to build on existing evidence from previous vaping and smoking cessation research undertaken by the study team. The effectiveness of combination nicotine replacement therapy (NRT) compared to nicotine tapering on vaping abstinence has not yet been investigated, but both provide an opportunity to increase success with vaping cessation, especially when combined with written behavioural support to further boost quit rates.

The planned trial will test whether using combination NRT will help more New Zealanders to quit vaping long-term, compared with a vape nicotine tapering plan. Participants in both groups will also receive written vaping cessation behavioural support.

Aim:

To evaluate the effectiveness, safety and acceptability of combination NRT plus behavioural support compared with vape nicotine tapering plus behavioural support, on six-month vaping abstinence.

Trial Design:

A single-blind, two-arm, pragmatic community-based randomised trial.

Eligibility criteria:

Eligible participants must live in New Zealand, vape nicotine at least weekly, used to smoke tobacco regularly but not in the past 6-months OR have never smoked tobacco, are aged ≥16 years, and have no contraindications to the study treatment. Participants must be motivated to quit-vaping in the next eight weeks, have access to the internet, and be able to provide consent. Participants must also have no treatment preference (i.e., they are happy to use whatever treatment they are allocated). 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, low socio-economic groups, and people with disabilities, given their disproportionately higher prevalence of vaping. 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, body mass index, vaping history, vaping dependence, motivation to quit, signs and symptoms of nicotine withdrawal and urge to vape, smoking history, alcohol use, cannabis use, self-reported comorbidities, health-related quality of life, and concomitant medication. Full details on the baseline data are provided later in this trial registration. Once participants complete and submit the baseline form, they will be randomised to one of the two trial treatment groups and immediately notified of their allocated intervention.

Randomization:

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 (1:1 ratio) to one of two trial groups using stratified block randomisation (using varying block sizes), and stratified by ethnicity (Māori, non-Māori) and smoking status (never smoked, used to smoke). The randomisation sequence will be generated by the trial statistician, and centrally managed and concealed until the point of randomisation.

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 finalised and uploaded to the trial registry prior to the first participant being randomised.

Interventions:

Participants will be randomised to eight weeks of: 1) combination NRT (21mg patch plus 1mg mouth spray) or 2) a written vape nicotine tapering programme. Tapering will be based on the participants current e-juice nicotine concentration and frequency of vaping upon entry to the trial. Participants will use their own vapes and nicotine e-liquid. All participants will also receive written behavioural support which will focus on building self-efficacy and relapse prevention. All interventions 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 'end of treatment' call (i.e., eight weeks after treatment delivery).

Follow-up:

Participants will be asked to begin their treatment the day after they receive their courier pack. Participants will be advised to continue with their allocated treatment, irrespective of any lapses back to vaping (or smoking), with the aim to be vape-free by the end of eight weeks (the designated quit date and end of treatment). All follow-up calls will be anchored to end of treatment (i.e., eight weeks after treatment delivery), whether they started or completed treatment.

Outcome data:

The primary outcome is being vape-free and tobacco-free, defined as self-reported continuous abstinence from vaping at six-months post-end of treatment. Specifically, self-report of no device use (defined as not vaping more than five vaping sessions since end of treatment), and no use of any tobacco products (defined as not smoking more than five cigarettes since end of treatment and no use of any other tobacco products since end of treatment), but individuals may or may not be using NRT. The primary outcome is partially validated. There is no vaping-specific biomarker available, so verification of 'vape-free' status can't be validated. However, tobacco-free status will be verified using exhaled carbon-monoxide (CO) measurement with a Bedfont Smokerlyzer (≤5 ppm signifying abstinence). Outcomes collected at end of treatment, then one-, three-, and six-months post end of treatment include other cessation outcomes, lapse/relapse to vaping, relapse to smoking in people who used to smoke, treatment adherence and compliance, other vaping support, signs and symptoms of nicotine withdrawal and urge to vape, cross-over, acceptability, recommendation of treatment to others, continuation of treatment, cannabis and alcohol use (six months only), change in body mass index, change in health state, serious adverse events, health-related quality of life, cost outcomes, concomitant medication, and participant experience in the trial. Full details on the outcome data are provided later in this registration.

Trial power:

A total of 774 participants (387 per group) will provide 90% power at p=0.05 to detect an absolute difference of 11% in self-reported six-month continuous abstinence rates (Vape-free and tobacco-free) between the combination NRT plus behavioural support group and the vape nicotine tapering plus behavioural support group. We have assumed that the self-reported six-month continuous abstinence vaping quit rates (vape-free and tobacco-free) for those in the NRT group will be 26%, compared to 15% in the nicotine tapering group. 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 combination NRT plus behavioural support compared with the vape nicotine tapering plus behavioural support. 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:

* Live in New Zealand.
* Vape nicotine at least weekly (one or more days out of the past seven days).
* Used to smoke (i.e. they have smoked tobacco regularly but not at all in the past six months) or have never smoked (i.e., they have never been a regular user of smoked tobacco, defined as less than 100 cigarettes in their lifetime).
* Are aged ≥16 years.
* Are motivated to quit vaping in the next eight weeks.
* Are able to provide consent.
* Have access to the internet via a computer or smart phone.
* Are a registered patient at a New Zealand medical facility.

Exclusion Criteria:

* They have another person in their household currently enrolled in the study.
* They smoke tobacco currently or were a recent regular user of tobacco.
* They are enrolled in another vaping cessation programme/trial.
* They self-report having had a serious cardiovascular event, or hospitalisation for a cardiovascular complaint, in the previous four weeks (e.g. stroke, myocardial infarction, unstable angina, cardiac arrhythmia, coronary artery bypass graft and angioplasty).
* They self-report uncontrolled hypertension.
* They have a strong preference to use/not use NRT or nicotine tapering.
* They are current users of smoking cessation pharmacotherapy (e.g. NRT, varenicline, cytisine, nortriptyline \[including if it is used for a different indication\], and amitriptyline \[as it converts to nortriptyline\].
* They are currently enrolled in another vaping cessation programme/trial.