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Trial registered on ANZCTR


Registration number
ACTRN12625000179437
Ethics application status
Approved
Date submitted
18/12/2024
Date registered
14/02/2025
Date last updated
14/02/2025
Date data sharing statement initially provided
14/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Puff vs Pill: Break the Habit Study: Effect of Nicotine Vaping Products vs Varenicline on Smoking Cessation Among People Experiencing Social Disadvantage.
Scientific title
Effect of Nicotine Vaping Product vs Varenicline on Smoking Cessation Among People Experiencing Social Disadvantage: A Randomised Controlled Trial
Secondary ID [1] 313197 0
Nil known
Universal Trial Number (UTN)
U1111-1257-3906
Trial acronym
BHS - Break the Habit Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco Smoking 335469 0
Condition category
Condition code
Public Health 332030 332030 0 0
Health service research
Mental Health 332031 332031 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nicotine vaping products (NVPs) in the form of two “pod” devices either prefilled [Alt] and refillable [Rift] with nicotine salt e-liquids containing nicotine (4%;40mg/ml) in tobacco or mint flavours for 12 weeks. For each device a USB charger will be provided, as well as a shared wall adaptor. Participants will be provided with detailed instructions on how to use the vaping products, along with a wallet card and fridge magnet with product use and safety information for quick access. Participants are advised to use the study product ad libitum throughout the day to either mitigate or satiate the urge to smoke tobacco products. They are encouraged to stop using the devices once they no longer feel the urge to smoke.

The alt. device has replaceable pre-filled 2ml pods that contain 40mg/ml nicotine salt e-liquid in either tobacco or mint flavour. The Rift device has a refillable 2ml pod, and is supplied alongside 40mg/ml nicotine salt e-liquid (provided in 30ml bottles) in tobacco and mint flavours.

NVPs will be delivered to participants in two mailed deliveries. Both deliveries will be sent by a central pharmacy directly to participants. The first delivery (“Initiation Pack”) will be provided after the baseline interview. will receive both prefilled (alt.) and refillable (Rift) devices in mint and tobacco flavours as part of the initiation packs, as well as nicotine liquid in two flavours (tobacco, and mint) for both. The second delivery (“Maintenance Pack”) will be available after the first check-in call, 2-4 weeks after baseline. Participants will have the choice of either having each device and flavour as they had in the Initiation Pack or any combination of devices and flavours, as well as replacement batteries for the devices. Participants who do not complete their first check-in call or are not using the study products at the time of the first check-in call, will receive a letter in place of the study products instructing them to call the study toll free number if they change their mind and wish to continue using the study products

The ingredients for tobacco and mint e-liquids are the same for both the alt and rift device, and include tobacco and mint flavouring respectively, as well as glycerol, propylene glycol, and nicotine (as benzoate).

Adherence will be monitored via two check-in calls, check-in call 1 and 2, occurring between 2-4 weeks and 8-10 weeks respectively.

In addition to the two packs which are provided free of charge, at check-in call 2 the participants are also offered a prescription for further three months supply of nicotine vaping products. The prescription allows participants to purchase NVPs at pharmacies that supply them, at their own cost.

Follow ups will occur with the participant at 4 months and 12 months post-baseline. The former will be an online survey and the latter a telephone interview. They will measure participant’s adherence to the treatment and the additional behavioural support.

Participants are also provided 12-week text message behavioural quit support with the option to opt-out at any stage if desired. As part of the text message support program, participants will receive a mix of quit smoking support text messages with content including information on how to use the study products, coping with nicotine withdrawal symptoms, study progress updates, and motivational ‘feel good’ messages. A mix of text, emojis, and links to resources such as videos, websites, and Graphics Interchange Format (GIF) images, will be used throughout the text program to promote engagement with the program.

The text message program has been developed based on similar programs used in two prior smoking cessation studies (Trial Id: ACTRN12621000076875, n = 1058 and (Trial Id: ACTRN12622000820707, n = 1246).

The development of the original program (Trial Id: ACTRN12621000076875) was informed by the World Health Organization’s (WHO) Be He@lthy, Be Mobile handbook (World Health Organization, 2015). This handbook outlines key considerations for implementing large-scale tobacco cessation messaging programs and guided the development of the text message support framework. An expert advisory group (clinical trialists, smoking cessation specialists and text messaging specialists) further refined the program and ensured both general quit support provision and also dedicated content was provided which was treatment-specific (i.e. text message support regarding use of allocated treatment group e.g. either nicotine replacement therapy of nicotine vaping products), The text program also provided support regarding strategies for managing nicotine withdrawal and side effects, study progress updates, goal setting, relapse prevention, and motivational messages.

This original program was then adapted for a subsequent trial of a more tailored and longer text message program intervention (Trial Id: ACTRN12622000820707) and the current study. In the current study, the program was adjusted to include varenicline-specific messages for this treatment arm, as well as adjusted program length/text frequency. These amendments were made through consultation with the Trial Steering Committee and a Community and Consumer Advisory Committee (CCAC) (comprising current/ex-smokers from previous studies). The Trial Steering Committee reviewed the messaging to maintain consistency across treatment groups and enhance participant comprehension. The Community and Consumer Advisory Committee provided valuable insights and feedback that helped refine language, optimize message timing, and ensure messages were practical and supportive. Final content was endorsed by all CCAC members.

In summary, the current text message program is the result of iterative development, empirical testing, and extensive stakeholder consultation across multiple studies and advisory committees.
Intervention code [1] 329773 0
Treatment: Devices
Intervention code [2] 329774 0
Behaviour
Comparator / control treatment
Participants allocated to the varenicline group will be provided with varenicline tablets for up to 12 weeks. Dosage will be in accordance with the product information. For the first week the dosing schedule comprises the following:
• Days 1-3: one white 0.5mg tablet once a day
• Days 4-7: one white 0.5mg tablet twice daily (morning and night)
• Day 8 – end of treatment: one blue 1mg tablet twice a day (morning and night)

Treatments will be mailed to participants by a central pharmacy. The study products will be posted to participants on two occasions akin to the intervention schedule. The first delivery (Initiation Pack) will be mailed after the baseline interview and the second delivery (Continuation Pack) will be sent after the first check-in call has been completed (2 to 4 weeks post-baseline interview ).

The Initiation Pack will include 11 x 0.5 mg tablets that will be sufficient supply for 7 days, and 42 x 1mg tablets (total of 53 tablets) which is sufficient for a further 21 days. The Continuation Pack will consist of 112 x 1 mg tablets (sufficient for 56 days). In addition to the two packs which are provided free of charge, at check-in call 2, the participants are also offered a prescription for further three months supply of varenicline. The prescription allows participants to purchase varenicline at pharmacies that supply them, at their own cost.

Check-in calls, interviews, and surveys, as well as the 12-week text message program will be identical to the intervention group (except in that questions, information, and help will be regarding varenicline as opposed to NVPs)
Control group
Active

Outcomes
Primary outcome [1] 340186 0
Carbon monoxide (CO) verified 6-month continuous abstinence at 12-month follow-up. Continuous 6- month abstinence will be defined as having remained quit for 6 months with the additional criterion of no slip-ups (not even a puff), and a CO level of less-than-or-equal-to 5 parts per million (ppm) in expired breath.
Timepoint [1] 340186 0
The breath test will take place shortly after the final follow up interview (if the participant meets the criterion of continuous abstinence) that will occur at 12 months after the baseline interview completion date.
Secondary outcome [1] 443217 0
Self-reported continuous abstinence for 6 months: defined as self-report of not smoking (not even a puff) for at least six months preceding final follow up at 12 months.
Timepoint [1] 443217 0
The final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [2] 443218 0
Self-reported 7-day point prevalence abstinence: defined as self-report of having smoked no cigarettes (not even a puff) in the past 7 days.
Timepoint [2] 443218 0
4 timepoints: Check-in call 1 (2-4 weeks); check-in call 2 (8-10 weeks); 4-month follow-up survey and the final 12-month follow-up interview.
Secondary outcome [3] 443219 0
Change in number of cigarettes smoked from baseline to final follow up at 12 months.
Timepoint [3] 443219 0
The final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [4] 443220 0
Use of varenicline or NVP at final follow up
Timepoint [4] 443220 0
The final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [5] 443221 0
Other health resource use: including hospital in- and out-patient visits, GP visits, pharmaceutical co- payments, home and continuing care (if any), and over the counter (OTC) medication use.
Timepoint [5] 443221 0
The questions on the access to different services are collected during the baseline interview and the PBS and MBS data will be provided to the study team by Services Australia.
Secondary outcome [6] 443223 0
The proportion of self-reported AEs and SAEs will be compared across the varenicline and NVP groups.
Timepoint [6] 443223 0
3 timepoints: Check-in call 1 will occur between 2-4 weeks; check-in call 2 will occur between 8-10 weeks; and the final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [7] 443224 0
Change in self-reported respiratory symptoms.
Timepoint [7] 443224 0
4 timepoints: Check-in call 1 will occur between 2-4 weeks; check-in call 2 will occur between 8-10 weeks; 4 month follow-up; and the final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [8] 443225 0
Participants’ treatment adherence and compliance measured by responses about their quit-attempt and study product use/adherence.
Timepoint [8] 443225 0
4 timepoints: Check-in call 1 will occur between 2-4 weeks; check-in call 2 will occur between 8-10 weeks; 4 month follow-up; and the final follow-up interview will occur 12 months after the baseline interview completion date.
Secondary outcome [9] 444683 0
Change in self-reported respiratory symptoms.
Timepoint [9] 444683 0
4 timepoints: Check-in call 1 will occur between 2-4 weeks; check-in call 2 will occur between 8-10 weeks; 4 month follow-up; and the final follow-up interview will occur 12 months after the baseline interview completion date.

Eligibility
Key inclusion criteria
Participants can be included if they meet the following criteria:
• Aged 18 years or older;
• Receiving a government pension, support, or allowance (proxy for low-SES)*;
• Person who currently smokes tobacco daily** and wanting to quit tobacco smoking;
• Willing to use varenicline or NVPs in next quit attempt;
• Willing to make a quit attempt on designated quit day (~8-14 days post-randomisation);
• Own a mobile phone that can receive and send text messages;
• Agree to receive text message behavioural quit support;
• Willing to complete telephone interviews for baseline, check-in calls and 12-month follow-up and a 4- month online survey;
• Available for follow-up over a 12-month period;
• Willing to allow research team to share the collected contact details for the purpose of:
-The Study Physician to make contact if required and if they need more information about health status and to inform the UNSW
research team of their decision;
-Research staff from UNSW or central pharmacy (Chemist Warehouse, Virginia, QLD) mailing out the study
products;
• Able to understand and communicate in English;
• Able to provide informed consent.
*Low-SES is a diverse construct, and receipt of a pension or allowance will be used as a proxy for low-SES and marker for social disadvantage in this trial, as recipients must satisfy a government’s means-test which considers both an individual's and their partner's income and assets, where approval is only granted if both are below a specified threshold.

**Use of any combustible tobacco-containing product on a daily basis at time of screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnant, breast-feeding, or planning pregnancy in the next 12 months;
• Current participation in another quit smoking program or study, or previously enrolled in this study;
• Current use*** of any quit smoking medications or products (i.e., NRT, bupropion [Zyban], varenicline [Varenapix], cytisine, NVPs/ e-cigarettes containing nicotine, nicotine inhalers or any other quit smoking medications or products)***;
• Allergies or hypersensitivity to either varenicline or nicotine-containing e-liquids, or any excipients;
• End stage or severe renal diseased;****
• Deemed medically unfit, by the Study Physician, to participate at the time of screening.
***Current use will be defined as use of product on the same day as screening.
****Exclusion criterion specific to varenicline.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The database system (REDCap) will assign participants treatment groups using a computer pre-generated randomisation list embedded in the system. To conceal the allocation list from those at the TCC, an independent statistician will have access to the pre-generated randomisation list and will upload this to REDCap.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Following baseline CATI completion, REDCap will randomly assign each participant to one of the treatment groups in a 1:1 ratio. The permuted block randomisation will use unequal block sizes of 4 and 8.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will be pre-specified. Baseline characteristics of the varenicline and NVP groups will be presented using frequency and percentages for categorical variables and means/standard deviations or medians/interquartile ranges for continuous measures. A Bayesian beta-binomial posterior distribution for the quit proportions will be constructed for the varenicline and NVP groups separately and one million random draws from each posterior distribution will be taken. Superiority of NVPs over varenicline will be established if the posterior probability of quitting in the NVP arm is greater than corresponding posterior probability in the varenicline arm in 97.5% of random draws. A non-informative beta prior will be used for the primary analysis, but sensitivity analyses will use informative beta priors based on the most recently published Cochrane review data for varenicline and NVPs. A similar Bayesian analysis will be conducted for the proportions of SAEs and AEs in each study arm. 95% credible intervals (CrIs) will be reported for abstinence rates in each arm and for the difference in quit proportions.

The primary effectiveness outcome for this study will use the Russell Standard criteria. Primary analysis will be conducted considering individuals with missing smoking status at follow-up as treatment failures. Sensitivity analyses will involve: (1) using multiple imputation to account for missing data; (2) excluding participants with missing data; and (3) excluding participants with protocol deviations. Secondary cessation outcomes of all time points will be modelled using generalized linear mixed models, which include time as a fixed effect and a random intercept to adjust for correlation of observations among individuals over time. Further details of all statistical analyses will be included in the statistical analysis plan (SAP).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2025
Actual
Date of last participant enrolment
Anticipated
1/04/2026
Actual
Date of last data collection
Anticipated
1/04/2027
Actual
Sample size
Target
872
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317632 0
Government body
Name [1] 317632 0
NHMRC Clinical Trials and Cohort Studies
Country [1] 317632 0
Australia
Primary sponsor type
University
Name
UNSW
Address
Country
Australia
Secondary sponsor category [1] 319943 0
None
Name [1] 319943 0
Address [1] 319943 0
Country [1] 319943 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316331 0
The University of New South Wales Research Ethics Committee A
Ethics committee address [1] 316331 0
Ethics committee country [1] 316331 0
Australia
Date submitted for ethics approval [1] 316331 0
22/12/2023
Approval date [1] 316331 0
11/04/2024
Ethics approval number [1] 316331 0
iRECS4324
Ethics committee name [2] 317014 0
Aboriginal Health & Medical Research Council Ethics Committee
Ethics committee address [2] 317014 0
Ethics committee country [2] 317014 0
Australia
Date submitted for ethics approval [2] 317014 0
17/09/2024
Approval date [2] 317014 0
19/12/2024
Ethics approval number [2] 317014 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137550 0
A/Prof Ryan Courtney
Address 137550 0
National Drug and Alcohol Research Centre, The University of New South Wales, Sydney NSW 2052
Country 137550 0
Australia
Phone 137550 0
+61 02 9065 7655
Fax 137550 0
Email 137550 0
r.courtney@unsw.edu.au
Contact person for public queries
Name 137551 0
Ryan Courtney
Address 137551 0
National Drug and Alcohol Research Centre, The University of New South Wales, Sydney NSW 2052
Country 137551 0
Australia
Phone 137551 0
+61 02 9065 7655
Fax 137551 0
Email 137551 0
r.courtney@unsw.edu.au
Contact person for scientific queries
Name 137552 0
Ryan Courtney
Address 137552 0
National Drug and Alcohol Research Centre, The University of New South Wales, Sydney NSW 2052
Country 137552 0
Australia
Phone 137552 0
+61 02 9065 7655
Fax 137552 0
Email 137552 0
r.courtney@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
We plan to share fully anonymised individual participant data (IPD). All de-identified data of primary and secondary outcomes will be shared, excluding identifiable personal information (i.e., address details, contact information/details) and any relevant SAE/AE information.
When will data be available (start and end dates)?
Following publication, no end date
Available to whom?
Only bona fide research groups will be eligible to access data. Data access requests will be made via an application form detailing the specific requirements and the proposed research and publication plan. Data access requests will be reviewed against specific eligibility criteria by data custodians. Participants will consent for their anonymised data to be used in this way.
Available for what types of analyses?
Each application will be reviewed based on scientific quality and robustness of the proposed statistical analysis plan. Data request will be appraised by the Principal Investigator and wider Trial Steering Committee on a case-by-case basis with oversight of the Study Statistician.
How or where can data be obtained?
Access subject to approvals by Principal Investigator (r.courtney@unsw.edu.au) and following approval will be sent via secure file transfer.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24410Study protocol    The Study Protocol will be submitted to a peer rev... [More Details]



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