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Trial registered on ANZCTR


Registration number
ACTRN12621000076875
Ethics application status
Approved
Date submitted
13/10/2020
Date registered
29/01/2021
Date last updated
21/04/2023
Date data sharing statement initially provided
29/01/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Vaporised nicotine products versus nicotine replacement therapy for tobacco smoking cessation among low-socioeconomic status smokers: A randomised controlled trial.
Scientific title
Vaporised nicotine products versus nicotine replacement therapy for tobacco smoking cessation among low-socioeconomic status smokers: A randomised controlled trial.
Secondary ID [1] 302129 0
Nil known
Universal Trial Number (UTN)
U1111-1257-3906
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco smoking 318758 0
Condition category
Condition code
Public Health 316772 316772 0 0
Health service research
Mental Health 316773 316773 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vaporised nicotine product (VNP) devices (one tank device and one pod device) for 8 weeks plus 5-week Text Message behavioural quit Support (TMS) with the option to opt-out at any stage if desired. 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 TMS program to promote engagement with the program. Each device will be charged using the provided USB charger and wall adaptor. A replacement battery and replacement coils (5 pieces per pack) will also be provided.

The VNP tank device used is the Innokin Endura T18 Personal Vaporizer, which has a refillable 2.5ml tank for the e-liquid (18mg/ml nicotine). Three e-liquid flavours will be provided: tobacco, menthol and a fruit flavour. The study will have three e-liquid suppliers to guarantee ongoing supply throughout the study: Lumo Liquid in 10ml bottles; VAPO e-liquid in 30ml bottles; and DashVapes e-liquid in 30ml bottles.

All e-liquids are 18mg/ml in strength. Lumo Liquid ingredients are as follows (w/w): tobacco flavouring (1.19%), nicotine (1.60%), vegetable glycerine (24.56%), propylene glycol (73.24%); menthol flavouring (4.83%), nicotine (1.60%), vegetable glycerine (22.99%), propylene glycol (71.18%); strawberry flavouring (0.63%), nicotine (1.60%), vegetable glycerine (33.00%), propylene glycol (71.00%). VAPO e-liquid additional flavour ingredients are as follows (w/w): tobacco flavouring (25.88%), nicotine (17.25%), vegetable glycerine (36.53%), propylene glycol (20.34); menthol flavouring (21.03%), nicotine (17.25%), vegetable glycerine (41.85%), propylene glycol (20.09%); berry flavouring (27.50%), nicotine (17.25%), vegetable glycerine (39.42%), propylene glycol (15.83%). DashVapes e-liquid additional flavour ingredients are as follows (v/v): tobacco flavouring (10.00%), nicotine (1.80%), propylene glycol (40.00%), vegetable glycerine (48.20%); menthol flavouring (10.00%), nicotine (1.80%), propylene glycol (40.00%), vegetable glycerine (48.20%); and strawberry flavouring (10.00%), nicotine (1.80%), propylene glycol (40.00%), vegetable glycerine (48.20%);

The VNP pod device is the Alt. Pod personal vaporiser. The pod device uses nicotine salt pods (4%; 40mg/mL). Alt. Pod ingredients are as follows (w/v): tobacco flavour (12%), nicotine (4%), benzoate (4%), propylene glycol (30%), vegetable glycerine (50%); menthol flavour (15%), nicotine (4%), benzoate (4%), propylene glycol (27%), vegetable glycerine (50%); mango flavour (20%), nicotine (4%), benzoate (4%), propylene glycol (17%), vegetable glycerine (55%).

Participants are asked to use the study product ad libitum throughout the day and encouraged to stop smoking completely, or reduce smoking if unable to stop completely. Participants will be provided with detailed instructions on how to use the VNP devices effectively. The e-liquid will be provided in dropper bottles with childproof caps.

Adherence will be monitored via two check-in calls in the first four weeks of the treatment period. These check in calls will also assess smoking status, treatment adherence, adverse events (AEs) or serious adverse events (SAEs), and any changes to concomitant medication at these time points.
Intervention code [1] 318425 0
Treatment: Drugs
Intervention code [2] 318426 0
Treatment: Devices
Intervention code [3] 318427 0
Behaviour
Comparator / control treatment
Oral nicotine replacement therapy (NRT) (4mg nicotine gum/lozenge) for up to 8 weeks plus 5-week text message behavioural quit support. An unbranded carry case will also be provided.
For the oral NRT, participants can choose gum or lozenge (4mg) and will be instructed to use the oral NRT when they have an urge to smoke, and to use up to 15 pieces per day. Participants will be provided with detailed instructions on how to use the NRT effectively and encouraged to stop smoking completely, or reduce smoking if unable to stop completely.
Adherence will be monitored via two check-in calls in the first four weeks of the treatment period. These check in calls will also assess smoking status, treatment adherence, adverse events (AEs) or serious adverse events (SAEs), and any changes to concomitant medication at these time points.
Control group
Active

Outcomes
Primary outcome [1] 324892 0
Carbon monoxide (CO) verified six-month continuous abstinence at seven-month follow-up. Continuous six-month abstinence will be defined as having remained quit for six-months (having smoked no more than five cigarettes in that time), and a carbon monoxide level of less-than-or-equal-to 5 parts per million. Only participants self-reporting continuous abstinence from smoking tobacco at final follow-up will be biochemically verified. Depending on the participants indicated preference, the CO breath test will be self-administered using an using a hand-held iCO™ Smokerlyzer® (using provided instructions), or administered by a trained researcher using a hand-held iCO™ Micro+™ Smokerlyzer® with a disposable, one-use mouthpiece. Both devices are non-invasive and require the participant to blow air into the device for 15 seconds to measure their CO level. An exhaled CO level of less-than-or-equal-to 5 parts per million will be considered abstinent.
Timepoint [1] 324892 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [1] 386119 0
Self-reported continuous abstinence: defined as self-report of smoking not more than five cigarettes at final follow-up.
Timepoint [1] 386119 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [2] 386120 0
Self-reported seven-day point prevalence abstinence: defined as self-report of having smoked no cigarettes (not even a puff) in the past seven days.
Timepoint [2] 386120 0
Check-in Call 1 will occur between the 9th and 15th day; Check-in Call 2 will occur between the 22nd and 28th day; and the final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [3] 386122 0
Cigarette consumption among continuing smokers (Number of cigarettes smoked per day; mean reduction and proportion of participants that achieved greater-than-or-equal-to 50% reduction of baseline cigarette consumption) at seven-month follow-up (~35 minutes; optional audio recording; conducted via telephone by a trained interviewer) to assess maintenance use and dual use.
Timepoint [3] 386122 0
Baseline interview and the final follow-up interview which will occur 7-months after the baseline interview completion date.
Secondary outcome [4] 386123 0
Participants’ treatment adherence and compliance measured by responses about their quit-attempt and study product use/adherence; collected during the baseline interview (~25 minutes; optional audio recording), 2-week and 4-week post-randomisation check-in calls (~10 minutes; not audio recorded) and seven-month follow-up interview (~35 minutes; optional audio recording). All interviews are structured telephone interviews conducted by a trained researcher and involve a combination of validated and study-specific questionnaires including the Tobacco withdrawal symptoms using Mood and Physical Symptoms Scale.
Timepoint [4] 386123 0
Check-in Call 1 will occur between the 9th and 15th day; Check-in Call 2 will occur between the 22nd and 28th day; and the final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [5] 386124 0
Use of NRT or VNP at final follow-up. The seven-month follow-up interview is an approximate 35 minute, structured telephone interview conducted by a trained interviewer and involves a combination of validated and study-specific questionnaires. Audio recording for quality assurance and to maintain the integrity of the trial, is optional and up to participants decision at the time of the interview. The questions adopted to assess NRT or VNP use at final follow-up are study-specific questions that are not derived from validated scales as we are assessing study-specific products.
Timepoint [5] 386124 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [6] 386125 0
Change in tobacco withdrawal symptoms measured by responses about tobacco withdrawal symptoms using the Mood and Physical Symptoms Scale; collected during the baseline interview (~25 minutes; optional audio recording), 2-week and 4-week post-randomisation check-in calls (~10 minutes; not audio recorded) and seven-month follow-up interview (~35 minutes; optional audio recording). All interviews are structured telephone interviews conducted by a trained researcher and involves a combination of validated and study-specific questionnaires.
Timepoint [6] 386125 0
Baseline interview (day 1); Check-in Call 1 will occur between the 9th and 15th day; Check-in Call 2 will occur between the 22nd and 28th day; and the final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [7] 387676 0
Change in financial stress (assessed using Index of Financial Stress).
Timepoint [7] 387676 0
Baseline interview and the final follow-up interview which will occur 7-months after the baseline interview completion date.
Secondary outcome [8] 387677 0
Change in mental distress stress (assessed via DASS-21)
Timepoint [8] 387677 0
Baseline interview and the final follow-up interview which will occur 7-months after the baseline interview completion date.
Secondary outcome [9] 387678 0
Use of quit services or products (e.g., Quitlines and quit aids) measured by responses about use of study products and other non-study quit support products/services; collected during the baseline interview (~25 minutes; optional audio recording) and the seven-month follow-up interview (~35 minutes; optional audio recording). All interviews are structured telephone interviews conducted by a trained interviewer and involves a combination of validated and study-specific questionnaires. The questions adopted to assess the use of quit services or products (e.g., Quitlines and quit aids), are study-specific questions that are not derived from validated scales as we are assessing study-specific products.
Timepoint [9] 387678 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [10] 387679 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 measured by responses about use of other non-study quit support products, services or resources/support (e.g. counselling); collected during the seven-month follow-up interview (~35 minutes; optional audio recording; structured telephone interviews conducted by a trained researcher; involves combination of validated and study-specific questionnaires) and from (consented) provision of Medicare Benefits Schedule (MBS) and/or Pharmaceutical Benefits Scheme (PBS) claims information by the Department of Human Services. MBS data will provide item-by-item data on Medicare funded GP visits and other MBS services used, date of use and co-payment required. PBS data will provide item-by-item data on the prescriptions filled, the associated co-payments for each prescription and the date the prescription was filled. The questions adopted to assess 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), are study-specific questions that are not derived from validated scales as we are assessing study-specific products.
Timepoint [10] 387679 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [11] 387680 0
The proportion of self-reported SAEs (e.g., heart surgery) and AEs (e.g., flu) will be compared across the NRT and VNP groups. In this trial an adverse event will include any illness, sign, symptom, or clinically significant abnormality that has appeared or worsened during the course of the clinical trial, regardless of its causal relationship to the treatment(s) under evaluation. All AEs will be carefully evaluated and tabulated using both patients preferred terms and MedDRA (Medical Dictionary for Regulatory Activities) coding. The severity will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (grade 1 – Mild AE, grade 2 – moderate AE, grade 3 – severe AE, grade 4 – life-threatening or disabling AE and grade 5 – death related to AE). Causality will be assessed using WHO criteria for causality assessment (certain, probable/likely, possible, unlikely, conditional/unclassified and un- assessable/unclassifiable). All SAEs will be assessed and reported to the sponsor and HREC in accordance with the trial protocol and the “National Health and Medical Research Council. Guidance: Safety monitoring and reporting in clinical trials involving therapeutic goods.”.
Timepoint [11] 387680 0
Check-in Call 1 will occur between the 9th and 15th day; Check-in Call 2 will occur between the 22nd and 28th day; and the final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [12] 387681 0
Changes in respiratory symptoms measured by responses about respiratory symptoms using the Lower respiratory tract infections-Visual analogue scale and Modified Medical Research Council dyspnoea scale; collected during the baseline interview (~25 minutes; optional audio recording), 2-week and 4-week post-randomisation check-in calls (~10 minutes; not audio recorded), and seven-month follow-up interview (~35 minutes; optional audio recording). All interviews are structured telephone interviews conducted by a trained researcher and involve a combination of validated and study-specific questionnaires including the Lower respiratory tract infections-Visual analogue scale (LRTI-VAS) and the Modified Medical Research Council (MRC) dyspnoea scale.
Timepoint [12] 387681 0
Baseline interview (day 1); Check-in Call 1 will occur between the 9th and 15th day; Check-in Call 2 will occur between the 22nd and 28th day; and the final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [13] 387682 0
User experience of VNP devices and e-liquid flavours measured by responses about user experience of vaporiser devices (hand-held Alpha Tank or Alt Pod vaporiser) and nicotine e-liquid flavours used; collected during the seven-month follow-up interview (~35 minutes; optional audio recording; structured telephone interviews conducted by a trained researcher; involves combination of validated and study-specific questionnaires). The questions adopted to assess user experience of VNP devices and e-liquid flavours, are study-specific questions that are not derived from validated scales as we are assessing study-specific products.
Timepoint [13] 387682 0
The final follow-up interview will occur 7-months after the baseline interview completion date.
Secondary outcome [14] 389287 0
Continued use of nicotine products at seven-month follow-up (~35 minutes; optional audio recording; conducted via telephone by a trained interviewer) to assess maintenance use and dual use.
Timepoint [14] 389287 0
Baseline interview and the final follow-up interview which will occur 7-months after the baseline interview completion date.

Eligibility
Key inclusion criteria
Participants can be included if they meet the following criteria:
• willing to allow the research team and study clinician to access their data for quality assurance and to maintain the integrity of the trial;
• 18 years of age or older;
• receiving a government pension or allowance (proxy for low-SES);
• are a current daily smoker;
• interested in quitting smoking and using the study products;
• willing to make a quit attempt in the next two weeks;
• have a mobile phone that can receive text messages;
• available for follow-up over a 7-month period;
• agree to use the allocated study product and refrain from using another quit smoking medication whilst using the study products;
• willing to receive daily quit support text messages during the treatment period (with the option to opt out during the study);
• speak English and can provide consent;
• willing to allow the research team to share the collected contact details for the purpose(s) of (i) the study doctor to make contact if required, (ii) the Social Research Centre to conduct two telephone interviews, and (iii) research staff from UNSW or a third-party contracted research organisation mailing out the study products;
• willing for the study clinician to call if they need more information about health status and to inform the UNSW research team of their decision;
• willing to complete two telephone check-in calls with the UNSW research team; and
• willing to complete baseline and follow-up telephone interviews with the SRC.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they are:
• currently participating in another quit smoking program or study;
• currently using any quit smoking medications or products (i.e. NRT, bupropion [Zyban], varenicline [Champix], clonidine, nortriptyline, cytisine, vaporised nicotine product/electronic or e-cigarettes/inhalers or other quit smoking medication or product);
• diagnosed with unstable angina (i.e. chest pain that occurs suddenly and becomes worse over time, which happens seemingly without cause, where patient may be resting or asleep);
• hospitalised for stroke, heart attack, or another heart-related condition in the last two weeks;
• women who are pregnant, breastfeeding or planning to become pregnant in the next 7 months; and
• deemed medically unfit, by the study clinician, to participate at the time of screening (see below).

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)
Allocation will be completed by an external contract research organisation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Immediately after baseline data collection, all eligible participants will be randomised (block randomisation with unequal block sizes of 12 and 16) to either of the treatment arms in 1:1 ratio.
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
The trial will be single-blinded. The person collecting outcome data and the trial statistician will be blinded until database is locked and the primary analysis completed.

The participants and the administrative staff who perform day to day activities cannot be blinded due to the nature of the study and dissimilarities between treatment arms (i.e. treatment type and dosage form).
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will be pre-specified. Baseline characteristics of the NRT and VNP 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 NRT and VNP group separately and one million random draws from each posterior distribution will be taken. Superiority of VNP over NRT will be established if the posterior probability of quitting in the VNP arm is greater than corresponding posterior probability in the NRT 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 previously published results for NRT and VNP. 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.

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
Completed
Date of first participant enrolment
Anticipated
26/03/2021
Actual
30/03/2021
Date of last participant enrolment
Anticipated
8/04/2022
Actual
28/03/2022
Date of last data collection
Anticipated
30/11/2022
Actual
8/12/2022
Sample size
Target
1058
Accrual to date
Final
1058
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 306554 0
Government body
Name [1] 306554 0
National Health and Medical Research Council
Country [1] 306554 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
UNSW Sydney, NSW 2052
Australia
Country
Australia
Secondary sponsor category [1] 307080 0
None
Name [1] 307080 0
NA
Address [1] 307080 0
NA
Country [1] 307080 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306744 0
UNSW HREC
Ethics committee address [1] 306744 0
Ethics committee country [1] 306744 0
Australia
Date submitted for ethics approval [1] 306744 0
18/11/2019
Approval date [1] 306744 0
17/04/2020
Ethics approval number [1] 306744 0
HC191025

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

Contacts
Principal investigator
Name 104874 0
Dr Ryan Courtney
Address 104874 0
National Drug and Alcohol Research Centre
The University of New South Wales
Sydney NSW 2052 Australia
Country 104874 0
Australia
Phone 104874 0
+612 9065 7655
Fax 104874 0
Email 104874 0
r.courtney@unsw.edu.au
Contact person for public queries
Name 104875 0
Ryan Courtney
Address 104875 0
National Drug and Alcohol Research Centre
The University of New South Wales
Sydney NSW 2052 Australia
Country 104875 0
Australia
Phone 104875 0
+612 9065 7655
Fax 104875 0
Email 104875 0
r.courtney@unsw.edu.au
Contact person for scientific queries
Name 104876 0
Ryan Courtney
Address 104876 0
National Drug and Alcohol Research Centre
The University of New South Wales
Sydney NSW 2052 Australia
Country 104876 0
Australia
Phone 104876 0
+612 9065 7655
Fax 104876 0
Email 104876 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
8942Study protocol    The Study Protocol will be submitted to a peer rev... [More Details]
8943Statistical analysis plan  r.courtney@unsw.edu.au Access to the Statistical Analyses Plan is subject... [More Details]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseEffectiveness, safety and cost-effectiveness of vaporized nicotine products versus nicotine replacement therapy for tobacco smoking cessation in a low-socioeconomic status Australian population: a study protocol for a randomized controlled trial.2022https://dx.doi.org/10.1186/s13063-022-06644-8
N.B. These documents automatically identified may not have been verified by the study sponsor.