We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621000148875
Ethics application status
Approved
Date submitted
12/10/2020
Date registered
12/02/2021
Date last updated
12/02/2021
Date data sharing statement initially provided
12/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
HARMONY: Harm reduction for Opiates, Nicotine and You.

Scientific title
A trial of the effectiveness of vaporised nicotine products for tobacco smoking cessation amongst NSW opiate agonist treatment clients
Secondary ID [1] 302258 0
None
Universal Trial Number (UTN)
U1111-1245-6575
Trial acronym
HARMONY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco smoking 318983 0
Condition category
Condition code
Public Health 316955 316955 0 0
Health service research
Mental Health 317005 317005 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
HARMONY:
This is a randomised single blinded parallel group trial comparing a 12-week course of liquid nicotine delivered via Vaporised Nicotine Product (VNP) to best practice Nicotine Replacement Therapy (NRT) in a 1:1 ratio.
Condition 1: VNP
Participants randomised to Condition 1 shall be supplied with a VNP (Innokin Endura T18-II starter kit) and 12 weeks of prescribed liquid nicotine (Nicophar).
A one-week supply of (NRT) transdermal patches shall also be provided to participants randomised to Condition 1 for use whilst they are learning how to use the VNP effectively. Participants can use the VNP at their discretion, as they would smoke a cigarette. In addition to the VNP, liquid nicotine and NRT patches, participants will be shown the New Zealand website https://vapingfacts.health.nz/ and encouraged to visit the site as an online resource throughout the trial. Participants will also receive training in the forms of brief videos, information pamphlets, user manuals and interactive discussions with research staff.
Condition 1: VNP
• Device loaded with one bottle of 12mg/ml e-liquid
• An additional seven (7) bottles of 12mg/ml e-liquid
• A brief information session on how to use the VNP
• A VNP information pack including safe storage of e-liquid nicotine and disposal
• 1-week supply of nicotine patches
• Training on the use of NRT patches.
• Where possible, ensure that participant uses the VNP before leaving and leaves wearing an NRT patch.

Adherence will be measured via questionnaires.
Intervention code [1] 318547 0
Treatment: Drugs
Intervention code [2] 318548 0
Treatment: Devices
Intervention code [3] 318549 0
Behaviour
Comparator / control treatment
Condition 2: NRT
Participants randomised to Condition 2 shall be supplied with a combination of NRT transdermal patches and oral forms (inhalators, gum, lozenges, mouth spray) to use throughout the 12-week intervention period. In addition to the NRT, participants will be shown the New Zealand website https://vapingfacts.health.nz/ and encouraged to visit the site as an online resource throughout the trial.
Condition 2: NRT
• 28 x patches 21mg
• 2 x 20 pack of Inhalator 15mg
• 3 x canisters oral spray 13mg
• Training on the use of the NRT
• An NRT information pack including safe storage and disposal of used NRT products
• Where possible, ensure the participant leaves wearing an NRT patch and with an oral dose ready to use.
Control group
Active

Outcomes
Primary outcome [1] 325057 0
Self-reported 7day point prevalence abstinence from tobacco smoking assessed the following dichotomous question “In the last 7 days, have you smoked a cigarette, even a puff?

Timepoint [1] 325057 0
Week 12
Secondary outcome [1] 386702 0
Biochemically verified point prevalence abstinence

This will be measured via a CO monitor breath test for participants who self-report 7 day point prevalence abstinence at end of treatment
Timepoint [1] 386702 0
Week 12
Secondary outcome [2] 386919 0
Adverse Event (including Adverse Device Events)

Adverse events will be reported by participants with severity, expectedness and relatedness assessed by the Site Investigator or Study Doctor using information contained in the investigator’s brochure. Information collected concerning adverse events would also include onset date, resolution date, action taken (if any) and the outcome of the event.

Possible adverse events from electronic cigarettes include cough, dry mouth, throat irritation, mouth Irritation, headache and phlegm. Less common events may include indigestion, gas, and diarrhea, shortness of breath, irregular heartbeat, hiccups, dizziness, taste disturbance, dysgeusia (loss of taste), abdominal discomfort, nausea and vomiting. Nicotine withdrawal symptoms will not be recorded as adverse events.




Timepoint [2] 386919 0
Week 12
Secondary outcome [3] 386920 0
Self-reported 30-day continuous abstinence from tobacco smoking using a study-specific question "How many cigarettes have you smoked in the last 30 days?"
Response Options:
Less than 1 or just a puff
1-5
6-10
11-20
More than 20
Timepoint [3] 386920 0
Week 24
Secondary outcome [4] 386921 0
Self-reported 30-day continuous abstinence from all nicotine using a study specific question "Are you currently using any form of nicotine products, including vaporised nicotine products and tobacco products other than cigarettes?"
Response Options:
No
Yes, nicotine patches
Yes, oral nicotine products (gum, lozenges, inhalator, spray, strip)
Yes, nicotine vaping products
Yes, some other form of tobacco product (specify)
Timepoint [4] 386921 0
Week 24
Secondary outcome [5] 386922 0
Self-reported number of tobacco cigarettes smoked per day using a study specific question "Currently how many cigarettes do you smoke per day?"
Timepoint [5] 386922 0
Baseline, week 12 and week 24
Secondary outcome [6] 386923 0
Changes in nicotine craving and withdrawal symptoms

These will be assessed using Minnesota Nicotine Withdrawal Scale & Craving one item question “Currently, how often do you get strong cravings to smoke tobacco?”
1) Hourly or more often
2) Several times per day
3) At least once a day
4) Less than daily
Timepoint [6] 386923 0
Baseline, week 12 and week 24
Secondary outcome [7] 386924 0
Number and duration of relapse episodes

This will be measured using the Latency to Needing a Cigarette scale.
Timepoint [7] 386924 0
Week 12 and week 24
Secondary outcome [8] 386925 0
Treatment adherence

This is assessed using a study-specific questionnaire capturing nicotine product use and frequency.
Timepoint [8] 386925 0
Week 12 and week 24
Secondary outcome [9] 386926 0
Other substance use

This will be assessed using Australian Treatment Outcome Profile (ATOP)
Timepoint [9] 386926 0
Week 12 and week 24
Secondary outcome [10] 386927 0
Study retention

Retention is determined by number of completed research questionnaires
Timepoint [10] 386927 0
Week 12 and 24
Secondary outcome [11] 386928 0
A cost consequence study setting out a detailed comparative costs of treatments - from the perspective of health care provider and; primary and secondary outcomes of the VNP and NRT.

Costing items include public sources, wage awards, the Medical Benefits Schedule (MBS) and the Pharmaceutical Benefits Scheme (PBS); and research records such as costs of VNP products, inhalators, nicotine patches and gum, batteries and quitting aid materials. Where appropriate, consequences will be monetised and when inappropriate to monetise, they will be reported in their natural units.

Timepoint [11] 386928 0
Week 12
Secondary outcome [12] 389263 0
Nicotine withdrawal symptoms

These will be assessed using the Minnesota Nicotine Withdrawal Scale.
Timepoint [12] 389263 0
Week 12

Eligibility
Key inclusion criteria
Inclusion Criteria
• Provide written, informed consent to participate in the study.
• Aged 18 to 65 years
• Be accessing opioid agonist treatment from a participating service
• Current daily tobacco smokers on self-report
• Want to quit or cut down their tobacco smoking
• Be willing and able to comply with requirements of study (including having access to a phone)
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Currently breastfeeding or pregnant, or of childbearing potential and planning/trying to fall pregnant during the study period
• Current, severe medical disorder assessed by study medical officer (such as but not limited to, unstable cardiovascular/peripheral vascular disease, poorly controlled hypertension)
• Current, severe and unstable psychiatric disorder assessed by study medical officer (such as but not limited to, acute psychosis, severe anxiety and/or mood disorder, intent to harm self or others)
• Current enrollment in a clinical trial involving any investigational drug
• Regular use (more than one day per week) of VNP or e-Cigarette containing nicotine in the last 30 days
• Not available for follow-up (e.g. likely imprisonment or transfer out of service to another service that is not a trial recruitment site)

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 is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised in a 1:1 ratio between groups using variable block randomisation stratified by treatment site and then by cannabis use (no use versus use, recorded by baseline ATOP). A computer-generated randomisation schedule will be developed by an independent statistician and uploaded to the REDCap study database.
Allocation concealment will be ensured by applying rules and user rights within the REDCap database.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
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. The trial has been designed to conform to the CONSORT statement.
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / 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.

Aim 1: The primary outcome of interest will be proportion of people reporting abstinence at 3 months post treatment measured using 30-day 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. As recommended by the Russell Standard, the primary analysis will be intention-to-treat (ITT); all consenting participants in the cohort will be included in the analysis and those lost to follow-up for any reason, will be regarded as smokers. Sensitivity analysis will be performed using multiple imputation modelling, as well as appropriate techniques if the data are considered to be missing not at random (pattern mixture models for example).

Secondary aims: For the secondary outcomes a logistic regression model for abstinence outcomes will be used (verified continuous abstinence in those who report 7-day point prevalence abstinence at end of treatment (12 weeks) and self-report 30-day point prevalence abstinence at 3 months post-treatment) 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 be analysed using linear mixed models with a compound symmetry covariance structure.

Cost analysis: An economic cost-consequence study will be conducted from a health -provider perspective to capture:
i) the resources required to implement VNPs and NRT, and
ii) the consequence from each treatment.
The analysis will be designed to inform decisions made by health services on the provision of cessation services. The economic analysis will be interpreted with regard to the strength of evidence, acceptability of the interventions to stakeholders and their respective abilities to address issues of equity.

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
Recruitment hospital [1] 17527 0
Drug and Alcohol Clinical Services, Hunter New England Local Health District - Newcastle
Recruitment hospital [2] 17528 0
The Langton Centre - Surry Hills
Recruitment hospital [3] 17529 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [4] 17531 0
Cumberland Hospital - Westmead
Recruitment hospital [5] 17532 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 17533 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 17603 0
St George Hospital - Kogarah
Recruitment hospital [8] 17604 0
Campbelltown Hospital - Campbelltown
Recruitment postcode(s) [1] 31257 0
2300 - Newcastle
Recruitment postcode(s) [2] 31258 0
2010 - Surry Hills
Recruitment postcode(s) [3] 31259 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 31261 0
2145 - Westmead
Recruitment postcode(s) [5] 31262 0
2050 - Camperdown
Recruitment postcode(s) [6] 31263 0
2170 - Liverpool
Recruitment postcode(s) [7] 31348 0
2217 - Kogarah
Recruitment postcode(s) [8] 31349 0
2560 - Campbelltown

Funding & Sponsors
Funding source category [1] 306681 0
Government body
Name [1] 306681 0
NSW Ministry of Health Translational Research Grants Scheme
Address [1] 306681 0
Office of Health and Medical Research
Level 5, 73 Miller St North Sydney NSW 2060
Country [1] 306681 0
Australia
Primary sponsor type
Government body
Name
Hunter New England Area Health Service
Address
Hunter New England Local Health District
Drug and Alcohol Clinical Services
670 Hunter Street Newcastle NSW 2300
Country
Australia
Secondary sponsor category [1] 307232 0
University
Name [1] 307232 0
University of Newcastle
Address [1] 307232 0
University Drive
Callaghan NSW 2308
Australia
Country [1] 307232 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306859 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 306859 0
Level 3, Pod, HMRI
Lot 1, Kookaburra Circuit, New Lambton Heights NSW 2305
Ethics committee country [1] 306859 0
Australia
Date submitted for ethics approval [1] 306859 0
31/08/2020
Approval date [1] 306859 0
17/11/2020
Ethics approval number [1] 306859 0
HARMONY Project ETH01866

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. There is now good evidence of safety, and emerging evidence that VNPs assist cessation. More evidence of the safety and effectiveness of VNPs for populations (such as persons who use drugs) with high smoking prevalence rates and low quit rates is desperately needed. Further it is important to determine the efficacy of novel strategies compared to current best practice treatment, Nicotine Replacement Therapy (NRT). The aim of this trial is to test the effectiveness of VNPs at increasing smoking cessation amongst opiate agonist treatment (OAT) clients receiving treatment at alcohol and other drug (AOD) services across NSW Local Health Districts/Networks (LHD/Ns), compared to current best practice treatment (NRT). Service users from six LHD/Ns across NSW will be recruited and randomised.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105258 0
Prof Adrian Dunlop
Address 105258 0
Hunter New England Health Drug & Alcohol Clinical Services
Level 3, 670 Hunter Street
Building Newcastle Community Health Centre
Newcastle 2300
Country 105258 0
Australia
Phone 105258 0
+6124016 4664
Fax 105258 0
Email 105258 0
adrian.dunlop@health.nsw.gov.au
Contact person for public queries
Name 105259 0
Prof Adrian Dunlop
Address 105259 0
Hunter New England Health Drug & Alcohol Clinical Services
Level 3, 670 Hunter Street
Building Newcastle Community Health Centre
Newcastle 2300
Country 105259 0
Australia
Phone 105259 0
+61 2 4016 4664
Fax 105259 0
Email 105259 0
adrian.dunlop@health.nsw.gov.au
Contact person for scientific queries
Name 105260 0
Prof Adrian Dunlop
Address 105260 0
Hunter New England Health Drug & Alcohol Clinical Services
Level 3, 670 Hunter Street
Building Newcastle Community Health Centre
Newcastle 2300
Country 105260 0
Australia
Phone 105260 0
+61 2 4016 4664
Fax 105260 0
Email 105260 0
adrian.dunlop@health.nsw.gov.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?
All of the data collected in trial after de-identification
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years after following article publication
Available to whom?
Researchers who provide a methodically sound proposal
Available for what types of analyses?
To achieve the aims in the approved proposal only
How or where can data be obtained?
Proposals should be directed to Prof Adrian Dunlop and to gain access requestors will need to sign a data access agreement, data is available from Hunter New England Area Health Service. Prof Adrian Dunlop can be contacted via email on Adrian.Dunlop@health.nsw.gov.au
What supporting documents are/will be available?
Study protocol
How or where can supporting documents be obtained?
Type [1] 9256 0
Study protocol
Citation [1] 9256 0
The protocol will be published in a peer-reviewed open access journal during 2021 or available by request from adrian.dunlop@health.nsw.gov.au
Link [1] 9256 0
Email [1] 9256 0
Other [1] 9256 0
Attachment [1] 9256 0
Summary results
No Results