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).