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Trial registered on ANZCTR


Registration number
ACTRN12617000905369
Ethics application status
Approved
Date submitted
9/06/2017
Date registered
20/06/2017
Date last updated
7/06/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility of Electronic Nicotine Devices for Smoking Cessation With Alcohol and Other Drug Treatment Clients
Scientific title
The QuitENDs Study: A Feasibility Pilot Study of Electronic Nicotine Devices for Smoking Cessation With Alcohol and Other Drug Treatment Clients
Secondary ID [1] 292145 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco smoking 303585 0
Alcohol and other drug use 303586 0
Condition category
Condition code
Public Health 302992 302992 0 0
Other public health
Mental Health 302993 302993 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This proposal is for a trial aimed at exploring the feasibility, acceptability and potential effectiveness of the use of electronic nicotine devices (ENDs) as smoking cessation aids when used in conjunction with one of two commonly used quit smoking strategies: 'abrupt cessation' and 'gradual cessation'. Abrupt cessation involves smoking tobacco as normal until a designated quit day, followed by total abstinence. Gradual reduction strategies also
involve the designation of a quit day, however smokers utilizing this method aim to reduce or scale their intake of tobacco cigarettes prior to the quit day, usually according to a predefined schedule (i.e. a 25% reduction in tobacco cigarette consumption by week 1).
Treatment arms
The two intervention conditions: Group 1: Electronic Nicotine Devices abrupt cessation group (ENDs + abrupt) ; Group 2: Electronic Nicotine Devices gradual (ENDs + gradual).

Group 1 - Participants in Group 1 (Abrupt Cessation) will be asked to treat that day as their quit day and to start vaping (using their ENDs + liquid nicotine). For the following 12 weeks (treatment period) Group 1 participants will be asked to try and quit smoking cigarettes and replace their cigarettes with use of either, or both of their ENDs products.
The devices (Innokin Endura T22 and T18 starter kit) and refill liquid (Nicophar) were selected based on quality assurance and compliance with relevant standards (GMP for liquid). Participants will be provided with the END and an initial 4-week supply of liquid nicotine, with further supplies of the refill liquid mailed or couriered to them in 4 weekly intervals.
All participants will receive two different models of devices and a 12-week supply of one investigational medicine to be used within the trial period. The device is to be used in conjunction with the medicine.
Device: Innokin Endura T22
The Innokin Endura T22 is a simple to use device. Participants are required to turn the device on when they wish to use it, and inhale from the mouthpiece. To activate the heating coil to generate aerosol, the user presses and holds down a button while inhaling from the mouthpiece. This process causes the liquid nicotine (stored in the 4mL tank) to be heated by the coil and turned into an aerosol. The tank can be refilled with additional liquid nicotine as required and the 2000mAh battery recharged using a USB cable as needed. Given the large tank size and long battery life, the device does not require to be refilled and recharged as often as other devices, but is larger in size to accommodate these features. A device such as this may therefore be more appealing to heavier smokers.
Device: Innokin Endura T18
The Innokin Endura T18 is a slimline, pen style vaporiser. Similar to the Innokin Endura T22, the T18 device requires participants to turn the device on when they wish to use it, and inhale from the end. The liquid nicotine in this device is stored in a smaller 2.5mL tank located directly under the drip tip and can be refilled with additional liquid nicotine as required. The device is powered by a 1000mAh battery which can be recharged using the provided micro USB cable as needed. This device’s slimline design, smaller tank size and shorter battery life may be more appealing to light to moderate smokers interested in a more discrete vaporiser.

Liquid nicotine:
The liquid nicotine will be manufactured to GMP standards for the trial (Nicophar brand). It will be provided to participants in 10ml dropper bottles. The contents of each 10ml bottle will depend on the nicotine strength: 18mg or 12mg strength. Each 12mg strength 10mL bottle will contain nicotine (1.2%), Glycerol (84%) and water (14.8%). Each 18mg strength 10mL bottle will contain nicotine (1.8%), Glycerol (84%) and water (14.2%).
Liquid nicotine is designed to be used with an Electronic Nicotine Device (END) to
reduce/avoid symptoms of withdrawal from tobacco smoking, in a similar way that
other fast acting NRT products are used. The frequency with which the device (containing the liquid nicotine) is used will depend on the user, and their level of previous tobacco use. One strength of the liquid nicotine will be used (12mg nicotine/ml) which is a concentration that is in common use. The trial will supply in 10 mL pack size (total nicotine per pack =120mg for 1.2%). The strength of the eliquid is similar to a liquid nicotine product currently listed on the Australian Register of Therapeutic Goods, which is approved for over the counter sale in general retail outlets: Nicorette QuickMist Mouthspray, which contains 13.6mg/mL nicotine and each pack contains 13.2mL (i.e total nicotine per pack = 179.5mg nicotine). The trial will supply liquid nicotine for a 12 week period.

Adherence will be monitored via safety assessment calls and follow up up surveys in weeks 1, 3, 6 (survey), 7, 10, 12 (survey). We will also track unused liquid nicotine return at the conclusion of the study.
Intervention code [1] 298302 0
Treatment: Drugs
Intervention code [2] 298303 0
Treatment: Devices
Intervention code [3] 298304 0
Behaviour
Comparator / control treatment
For the ‘gradual reduction’ condition, participants will be asked to use the provided ENDs device/s and the liquid nicotine as a way of tapering or reducing the number/amount of tobacco cigarettes smoked during the treatment period, leading up to their designated quit date. Each week for the first 4 weeks of the treatment period they should reduce the number of cigarettes they smoke by 25% by replacing them with use of either, or both of their ENDs products. Cigarette smoking and use of ENDs will be assessed at 6 and 12 weeks post enrollment.
Control group
Active

Outcomes
Primary outcome [1] 302384 0
Smoking cessation: 7-day point prevalence, assessed by self-report and verified by carbon monoxide breath test
Timepoint [1] 302384 0
At baseline, and at 6 weeks and 12 weeks post study enrollment
Primary outcome [2] 302458 0
Smoking cessation: continuous abstinence, assessed by self-report in answer to the question 'Since [date of last follow-up] did you smoke at all, even part of a cigarette?'
Timepoint [2] 302458 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [1] 335798 0
Point prevalence abstinence from all nicotine (including ENDs) verified by carbon monoxide. Defined as having not used any products containing nicotine in the previous 7 days at assessment.
Timepoint [1] 335798 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [2] 335800 0
Cigarettes smoked per day assessed by questionnaire item designed for this study asked at 6 and 12 week time points.
Timepoint [2] 335800 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [3] 335801 0
This a composite secondary outcome. Cravings and withdrawal will be assessed by a standardized scale (Minnesota Nicotine Withdrawal Scale)
Timepoint [3] 335801 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [4] 335802 0
Time to relapse assessed by questionnaire item designed for this study.
Timepoint [4] 335802 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [5] 335803 0
Treatment adherence (use of ENDs) assessed by questionnaire items designed for this study.
Timepoint [5] 335803 0
At 6 weeks and 12 weeks post study enrollment
Secondary outcome [6] 335804 0
Process measures: Intervention Fidelity: Participant 12 week surveys will assess use of any additional pharmacotherapies, visits to GP, calls to Quitline and use of print and online materials.
Timepoint [6] 335804 0
At 12 weeks post study enrollment

Eligibility
Key inclusion criteria
Individuals must meet all of the following criteria to be enrolled in this study:
* Client of participating HNELHD AOD program
* Aged 18 years (or over)
* Current daily tobacco smoker
* Interested in making a serious quit attempt in the next 30 days
* Has not used an END containing nicotine in the past month
* Has capacity to consent and able to understand the participant materials and follow the study instructions and procedures (e.g. sufficient English language ability).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Individuals meeting any of the following criteria will be excluded from the study:
* Aged <18 years
* Currently pregnant or breast-feeding women (measured by self-report)
* Insufficient capacity to provide informed consent or complete the study requirements (e.g. completing surveys in English)

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)
Participants will be randomised on a 1:1 ratio to one of the two intervention groups using computer sequenced block randomisation. At the end of the baseline survey participants will be randomized to an intervention condition via a computer sequenced block randomisation embedded in the iPad.
Allocation is not concealed from the person conducting the study enrollment/baseline data collection.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised on a 1:1 ratio to one of the two intervention groups using computer sequenced block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We expect to recruit 50 clients over a 3 month period which is achievable in across two AOD clinic sites. Approximately 80% of AOD clients are smokers. We will be assuming 50% eligibility and consent into the trial, and 40% attrition at 12 weeks based on our current AOD research and thus approaching 130 service clients over the 3-month recruitment period. A total sample of 30 participants at 12 week follow-up will provide 15 smokers per experimental group. This pilot trial has been designed to provide essential information for the development of an adequately powered larger superiority trial, including smoking prevalence, response and attrition rates.

Statistical Analysis Plan
Data will be collected on recruitment and retention rates which will aid the design of future large trials. Primary cessation outcome analyses will be carried out on an intention to treat basis. Chi squared tests, relative risks and 95% CIs and 2-sided p-values for all binary variables, followed by adjusted multiple logistic regression analyses. Continuous outcomes (with 95% CIs) will be analysed using generalised linear mixed methods regression for the main aims, with adjustments for covariates where necessary.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 16394 0
2302 - Newcastle West

Funding & Sponsors
Funding source category [1] 296679 0
University
Name [1] 296679 0
University of Newcastle
Address [1] 296679 0
University Dr
Callaghan NSW 2308
Country [1] 296679 0
Australia
Funding source category [2] 296701 0
Charities/Societies/Foundations
Name [2] 296701 0
Hunter Medical Research Institute
Address [2] 296701 0
1/1 kookaburra circuit, New Lambton Heights NSW 2305
Country [2] 296701 0
Australia
Primary sponsor type
University
Name
The University of Newcastle
Address
University Drive
Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 295639 0
None
Name [1] 295639 0
Address [1] 295639 0
Country [1] 295639 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297907 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 297907 0
Hunter New England Local Health District
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 297907 0
Australia
Date submitted for ethics approval [1] 297907 0
07/12/2016
Approval date [1] 297907 0
16/02/2017
Ethics approval number [1] 297907 0
HREC/16/HNE/583

Summary
Brief summary
Smoking prevalence amongst people with alcohol and other drug (AOD) problems is extremely high. In Australia, up to 95% of people entering AOD treatment smoke tobacco, which is five times greater than for the general adult population. Although number of quit attempts are high, sustaining cessation is challenging for people with AOD dependence: many factors related to addiction, lack of cessation support and the high levels of smoking in their social network contribute to high relapse rates in this population. Nicotine Replacement Therapy (NRT) can reduce withdrawal symptoms and cravings and aid cessation, however our research with AOD users indicate they are hesitant to use traditional forms of NRT. Electronic Nicotine Devices (ENDs) hold significant potential as both cessation aids and harm reduction support. Unlike combustible tobacco cigarettes, ENDs deliver nicotine in an
inhalable form without the tobacco, hence removing many of the health harms associated with smoking.

This proposal is for a trial aimed at exploring the feasibility, acceptability and potential effectiveness of the use of electronic nicotine devices (ENDs) as smoking cessation aids when used in conjunction with one of two commonly used quit smoking strategies: 'abrupt cessation' and 'gradual cessation'. Abrupt cessation involves smoking tobacco as normal until a designated quit day, followed by total abstinence. Gradual reduction strategies also
involve the designation of a quit day, however smokers utilizing this method aim to reduce or scale their intake of tobacco cigarettes prior to the quit day, usually according to a predefined schedule (i.e. a 25% reduction in tobacco cigarette consumption by week 1).

Specifically, this study will aim to determine how the use of ENDs and liquid nicotine in conjunction with a 'gradual reduction' or 'abrupt cessation' quit strategy impacts smoking cessation or smoking reduction outcomes. It will determine whether the provision of ENDs assists smokers with AOD addiction to quit or reduce their tobacco consumption and whether using these devices reduces cigarette cravings and withdrawal symptoms. Finally, this study will evaluate whether AOD clients find ENDs devices acceptable as a quit smoking aid.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75426 0
Prof Billie Bonevski
Address 75426 0
School of Medicine & Public Health
Faculty of Health & Medicine
The University of Newcastle
University Drive
Callaghan NSW 2308
Country 75426 0
Australia
Phone 75426 0
+61 2 4033 5710
Fax 75426 0
+61 2 4033 5692
Email 75426 0
billie.bonevski@newcastle.edu.au
Contact person for public queries
Name 75427 0
Dr Olivia Wynne
Address 75427 0
School of Medicine & Public Health
Faculty of Health & Medicine
The University of Newcastle
University Drive
Callaghan NSW 2308
Country 75427 0
Australia
Phone 75427 0
+61 2 4033 5718
Fax 75427 0
+61 2 4033 5692
Email 75427 0
olivia.wynne@newcastle.edu.au
Contact person for scientific queries
Name 75428 0
Prof Billie Bonevski
Address 75428 0
School of Medicine & Public Health
Faculty of Health & Medicine
The University of Newcastle
University Drive
Callaghan NSW 2308
Country 75428 0
Australia
Phone 75428 0
+61 2 4033 5710
Fax 75428 0
+61 2 4033 5692
Email 75428 0
billie.bonevski@newcastle.edu.au

No data has been provided for results reporting
Summary results
Not applicable