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Trial registered on ANZCTR


Registration number
ACTRN12619001787178
Ethics application status
Approved
Date submitted
18/11/2019
Date registered
17/12/2019
Date last updated
17/12/2019
Date data sharing statement initially provided
17/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Project NEAT: NicotinE As Treatment for tobacco smoking following discharge from residential withdrawal services.
Scientific title
Project NEAT: A randomized controlled trial to examine the efficacy of Vaporised nicotine products and telephone quit line support compared with nicotine replacement therapy and telephone quit line support when used following discharge from a residential withdrawal services.
Secondary ID [1] 298065 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Project NEAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco smoking 312564 0
Condition category
Condition code
Public Health 311081 311081 0 0
Other public health
Mental Health 311082 311082 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Condition One: Vaporised Nicotine Products and Quitline.
Participants randomised to condition one will receive the following:
1) An information pack with study resources specifically designed by the investigators for the present study that include: a one page user VNP guide and a brochure that documents benefits of quitting smoking and tips on how to use the VNP, a study wallet card with trial number and study project phone line, letter to GP about study participation, brochure about Quitline;
2) Provision of two VNP kits (Innokin T18-II device);
3) A prescription of nicophar nicotine e-liquid (12mg/10ml) for 12-weeks. One initial and two re-fill prescriptions will be provided. A total of 24 units over the 12 weeks. The e-liquid containing nicotine is manufactured to GMP standards for the trial (Nicophar brand). It will be provided to participants in 10ml dropper bottles. Each 12mg strength 10ml bottle will contain nicotine (1.2%), vegetable glycerol (84%), and water (14.8%). Participants will be instructed to only use the study provided e-liquid in the provided device. Participants will be advised to use the VNPs ad libitum i.e. as and when required;
4) A one week supply of 21mg nicotine patches (7 patches to use for 7 days) will be provided to participants of the study. Participants will be encouraged to utilise the patches for the first week following discharge from the inpatient withdrawal service while they become accustomed to utilising the device;
5) Proactive referral to Quitline counselling (call-back service) which provides one call during their inpatient withdrawal treatment and then calls post discharge at days 1, 3, 7, 14 & 28 post-discharge, with an emphasis on relapse prevention. Average Quitline call is about 10-20 minutes, however, the total number and timing of calls will be tailored to client need and smoking status, i.e. more frequent calls around relapse crises/quit attempts with an approximate 10 calls over 12 weeks.

Check-in calls scheduled during weeks 1-10 post discharge will provide an opportunity to assess adherence with the allocated study products and opportunity to provide re-fills. Self-reported use of the VNP, NRT patches, and Quitline will also be gathered during the 3-month and 9-month follow-up surveys. Participants do not need to utilise all VNP, NRT patches, or Quitline for the entire study period to be able to participate.
Intervention code [1] 314298 0
Treatment: Drugs
Intervention code [2] 314299 0
Treatment: Devices
Intervention code [3] 314300 0
Behaviour
Comparator / control treatment
An active control condition will be used as it reflects what is expected of AOD services as part of routine care (but may not be routinely delivered).

Condition Two: Current Best Practice Treatment for Tobacco Smoking (Combination Nicotine Replacement Therapy and Quitline). Participants randomised to condition two will receive the following:
1) An information pack with study resources specifically designed by the investigators for the present study that include a one page user NRT guide and a brochure that documents benefits of quitting smoking and tips on how to use NRT;
2) Provision of 12 weeks of nicotine replacement therapy – transdermal (e.g. patches) and oromucosal forms (e.g. gum, lozenge, mouth spray) of NRT to be used throughout the intervention period. For weeks 1-4 participants will receive: 4 x QuitX 21mg Patches 7s, 2 x Nicorette Inahaltor 15mg 20s, and 3 x Nicorette Quick Mist 1mg spray. For weeks 5-8 participants will receive: 4 x QuitX 21mg Patches 7s, 2 x Nicorette Inhalator 15mg 20s, 1 x Nicorette Cool Drops 4mg 80s, and 1 x quitX Gum 4mg 100s Mint. For weeks 9-12 participants will receive 1 x Nicabate 21mg Patches 28s, 2 x Nicorette Inhalator 15mg 20, 2 x Nicorette Cool Drops 4mg 80s. Participants will be advised to use the NRT ad libitum i.e. as and when required. This will be mailed to an address the participant supplies;
3) Proactive referral to Quitline counselling (call-back service) which provides one call during their inpatient withdrawal treatment and then calls post discharge at days 1, 3, 7, 14 & 28 post-discharge, with an emphasis on relapse prevention. The total number and timing of calls will be tailored to client need and smoking status, i.e. more frequent calls around relapse crises/quit attempts with an approximate 10 calls over 12 weeks. Participants will be text messaged to alert them to expect a Quitline call prior to being called as AOD clients are unlikely to pick up calls from a private number. Counsellors will monitor and encourage correct use of NRT and work with clients to address barriers to its use.

Safety and product re-fill calls will provide an opportunity to assess adherence with the allocated study products. Self-reported use of the NRT and Quitline will also be gathered during the 3-month and 9-month follow-up surveys. Participants do not need to utilise all NRT or Quitline for the entire study period to be able to participate.
Control group
Active

Outcomes
Primary outcome [1] 319865 0
Self-reported 7 months continuous abstinence from tobacco smoking
This will be measured utilising a number of items specifically created for this study. Items include: a) duration since quitting smoking; b) occasions of smoking since quitting; c) occasions of smoking for a week; d) duration to week long relapse. These items together will inform whether individuals meet self-reported 7-month continuous abstinence from tobacco smoking.
Timepoint [1] 319865 0
9 months after inpatient withdrawal unit discharge
Secondary outcome [1] 370225 0
Biochemically verified 7 month continuous abstinence from tobacco smoking
A participant reporting that they have quit smoking for the last 7 months and have smoked on five or less than 5 occasions or not at all will be asked to complete a bedfront smokelyzer breath test to measure expired carbon monoxide (CO). A participant with a CO level less than 8ppm will be considered abstinent. The bedfont smokelyzer breath test will be conducted by a trained research assistant.
Timepoint [1] 370225 0
9 months after inpatient withdrawal unit discharge
Secondary outcome [2] 370226 0
30 day point prevalence abstinence
A composite measure will be used. The first item will ask participants "Have you smoked at all, even a puff, in the last 30 days?" with response options a) yes, b) no. A second measure will ask participants "How many cigarettes have you smoked in the last 30 days?" with response options a) less than 1 or just a puff; b) 1-5; c) 6-10; d) 11-20; More than 20. Both measures will be self-reported 30 day point prevalence abstinence and refers to the 30 days preceding the follow-up period in which the question is asked.
Timepoint [2] 370226 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [3] 370227 0
7 day point prevalence abstinence
This will be measured by asking participants "Have you smoked at all, even a puff, in the last 7 days?" with response options a) yes, b) no. This will be self-reported 7 day point prevalence abstinence and refers to the 7 days preceding the follow-up period in which the question is asked.
Timepoint [3] 370227 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [4] 370230 0
Number of cigarettes smoked
Participants will be asked "currently how many cigarettes do you smoke- per day, per week, and per month?". A reduction in the number of cigarettes per day, week, or month will be assessed compared to baseline.
Timepoint [4] 370230 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [5] 377927 0
Cravings to smoke
A composite measure will be used that examines frequency of cravings and strength or cravings as recommended in the smoking cessation literature. Frequency of cravings will be measured by asking participants "How often do you get cravings to smoke tobacco?" with response options: a) hourly or more often, b) several times per day, c) at least once a day, d) less than daily, e) never. Strength of cravings will be measured by asking participants "How strong have these urges been?" with response options: a) no urge, b) slight, c) moderate, d) strong, e) very strong, f) extremely strong.
Timepoint [5] 377927 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [6] 377928 0
Withdrawal symptoms
Assessment of withdrawal and psychological distress compared to baseline will be conducted using a measure that combines the Patient Health Questionnaire (PHQ-4) and Minnesota Nicotine Withdrawal Scale.
Timepoint [6] 377928 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [7] 377929 0
Relapse episodes
Relapse to tobacco smoking will be assessed by a composite measure designed for the study. The first measure will ask participants "Have you smoked at all since you quit?" with response options a) yes on more than 5 occasions; b) yes but on 5 or less occasions; c) no. The second measure will ask participants "Since you quit smoking, have you smoked every day for a week or more (even just puffs)" with response options a) yes; b) no; c) don't know; d) refused to answer. The third measure will ask participants "We need to start counting your quit attempt from the end of the last period when you smoked for a week or more" with response options a) 1 week to 1 month; b) 1-3 months; c) 3-6 months; d) More than 6 months.
Timepoint [7] 377929 0
3 and 9 months after inpatient withdrawal unit discharge
Secondary outcome [8] 377930 0
Abstinence from all nicotine/ tobacco products
This will be measured by asking participants "Are you currently using any form of nicotine products, including vaporised nicotine products and tobacco products other than cigarettes? with response options a) no; b) yes, nicotine patches; c) yes, oral nicotine products; d) yes, nicotine vaping products; e) yes, some other form of tobacco product.
Timepoint [8] 377930 0
3 and 9 months after inpatient withdrawal unit discharge

Eligibility
Key inclusion criteria
• Aged 18 or over
• Daily tobacco smoker (10 or more cigarettes) on entering withdrawal unit
• Accessing treatment from participating services
• Want to quit smoking in the next 30 days
• Has capacity to consent and able to understand the participant materials and follow the study instructions and procedure (e.g. sufficient English language ability and not too unwell as judged by medical staff)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Pregnant or breastfeeding
• Enrolled in another study
• Scheduled to be transferred to a long-term residential rehabilitation service following discharge from the withdrawal unit
• Used VNP (containing nicotine) in the last 30 days
• Currently engaged in Quitline’s call-back services
• No ready access to a phone

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)
While it is acknowledged that full concealment of allocation is not possible in trials where the participants are aware of treatments offered, this study will use partial blinding whereby randomisation will be performed by a biostatistician not involved with the study and follow-up assessors will be blind to allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation in permutated blocks of 4 or 6 will be conducted on a 1:1 allocation basis, stratified by service site. The randomisation module will be created in SAS, exported in the CSV file and saved in the randomisation module of the REDCap database.

Participants will be randomised to a study condition following completion of the baseline survey.
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 proposed study is a two-arm, single blinded, parallel group randomised trial with a 6-month post-intervention follow-up (or 9 months following discharge from the inpatient withdrawal unit). The trial has been designed to conform to the CONSORT statement.
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Statistical Analysis
Descriptive statistics will be used to present the baseline characteristics for intervention and control groups. All statistical tests will be two-tailed and conducted at the 5% significance level. The primary outcome of interest will be proportion of people reporting abstinence at 9 months post discharge measured using 7-months continuous abstinence measure. Differences between groups will be assessed using logistic regression. The model will include a term for treatment group while adjusting for potential confounders including service site. Odds ratios will be presented, together with 95% confidence intervals and likelihood ratio test p-values.

Secondary aims: For the secondary outcomes a logistic regression model for abstinence outcomes will be used (biochemically verified 7-month continuous abstinence, self-reported 30 day and 7 day point prevalence abstinence at 3 and 9months) unadjusted for other covariates, Number of cigarettes smoked per day will be compared at each time point using a negative binomial regression model. Craving and Withdrawal scores will be compared using ordinal logistic regression models. Change from baseline in each of the repeated measures and cigarettes smoked per day (in non-abstainers) will beanalysed using linear mixed models with a compound symmetry covariance structure.

Qualitative Analysis
The trial coordinators will analyse the qualitative data using an inductive thematic analysis approach with verification procedures. Data from clients, research assistants, service providers and Quitline staff will be analysed separately but all will be considered in interpretation of data.

Recruitment
Recruitment status
Not yet 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,QLD,VIC
Recruitment hospital [1] 13719 0
Belmont Hospital - Belmont
Recruitment hospital [2] 13720 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [3] 13721 0
Turning Point Drug and Alcohol Centre - Richmond
Recruitment hospital [4] 13722 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 26462 0
2280 - Belmont
Recruitment postcode(s) [2] 26463 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 26464 0
3121 - Richmond
Recruitment postcode(s) [4] 26465 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 302599 0
Government body
Name [1] 302599 0
National Health and Medical Research Council (grant number: G1800272)
Address [1] 302599 0
GPO Box 1421
Canberra ACT 2601
Country [1] 302599 0
Australia
Primary sponsor type
University
Name
The University of Newcastle
Address
Dr Paula Jones (Director- Research Services)
University Dr, Callaghan NSW 2308
Country
Australia
Secondary sponsor category [1] 302662 0
None
Name [1] 302662 0
Address [1] 302662 0
Country [1] 302662 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303234 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 303234 0
Location:
Research Ethics and Governance Office
The Lodge, Rankin Park Campus
Lookout Road,
New Lambton NSW 2305
Australia
Ethics committee country [1] 303234 0
Australia
Date submitted for ethics approval [1] 303234 0
01/05/2019
Approval date [1] 303234 0
05/09/2019
Ethics approval number [1] 303234 0
2019/ETH1055
Ethics committee name [2] 304033 0
The University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 304033 0
Research & Innovation Services Research Integrity Unit, The University of Newcastle
NIER, Block C
University Drive
Callaghan NSW 2308
Australia

Ethics committee country [2] 304033 0
Australia
Date submitted for ethics approval [2] 304033 0
14/08/2019
Approval date [2] 304033 0
Ethics approval number [2] 304033 0

Summary
Brief summary
Vaporised nicotine products (VNPs or electronic cigarettes) hold significant potential as both cessation aids and harm reduction support for people who smoke tobacco. It is important to determine the efficacy of novel strategies compared to current best practice treatment, Nicotine Replacement Therapy (NRT) and telephone Quitline. The aim of this world-first trial is to test the effectiveness of VNPs in conjunction with telephone Quitline at increasing smoking cessation amongst individuals receiving treatment at alcohol and other drug (AOD) residential withdrawal services compared to current best practice treatment (NRT and Quitline). Service users from six residential and inpatient withdrawal AOD services across three states (NSW, Victoria and Queensland) will be recruited and randomised. The intervention will be provided for 3-months post-discharge. Surveys will be conducted at 3 and 9-months post discharge and examine smoking cessation related variables.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 92946 0
Prof Billie Bonevski
Address 92946 0
School of Medicine and Public Health
Faculty of Health and Medicine
The University of Newcastle
1 University Drive
Callaghan NSW 2308
Country 92946 0
Australia
Phone 92946 0
+61 2 40335710
Fax 92946 0
+61 2 40335692
Email 92946 0
Billie.Bonevski@newcastle.edu.au
Contact person for public queries
Name 92947 0
Dr Eliza Skelton
Address 92947 0
School of Medicine and Public Health
Faculty of Health and Medicine
The University of Newcastle
1 University Drive
Callaghan NSW 2308
Country 92947 0
Australia
Phone 92947 0
+61 2 40335040
Fax 92947 0
+61 2 40335692
Email 92947 0
Eliza.Skelton@newcastle.edu.au
Contact person for scientific queries
Name 92948 0
Prof Billie Bonevski
Address 92948 0
School of Medicine and Public Health
Faculty of Health and Medicine
The University of Newcastle
1 University Drive
Callaghan NSW 2308
Country 92948 0
Australia
Phone 92948 0
+61 2 40335710
Fax 92948 0
+61 2 40335692
Email 92948 0
Billie.Bonevski@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results