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Trial registered on ANZCTR


Registration number
ACTRN12616001355460
Ethics application status
Approved
Date submitted
22/09/2016
Date registered
29/09/2016
Date last updated
2/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Varenicline alone or with nicotine e-cigarettes for smoking cessation in people with mental illness and drug and/or alcohol dependence.
Scientific title
A randomised controlled clinical trial to evaluate the effectiveness and safety of combining varenicline with nicotine e-cigarettes on smoking abstinence in people with co-existing mental health and drug and alcohol dependence conditions.
Secondary ID [1] 290195 0
None
Universal Trial Number (UTN)
U1111-1186-7693
Trial acronym
STATUS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking 300350 0
Mental illness 300351 0
Drug and alcohol dependence 300399 0
Condition category
Condition code
Mental Health 300220 300220 0 0
Addiction
Mental Health 300240 300240 0 0
Other mental health disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive behavioural support phone calls of around 10 minutes duration, twice weekly, delivered by trained research assistants, for the first 6 weeks after randomisation. The calls will follow a standard format and content that includes encouragement to stay abstinent, avoid cues to relapse, tips for dealing with cravings and so on.

Varenicline tartrate 0.5 mg and 1 mg tablets (Pfizer); taken orally twice daily following a 2-week up-titration: Days 1 – 3: 0.5 mg once daily; Days 4 – 7: 0.5 mg twice daily; Day 8 –14 :1 mg twice daily. Day 15 (randomisation date) - end of Week 10: 1 mg twice daily.

PLUS
E-cigarettes with nicotine, inhaled ad libitum, 18 mg (Joyetch AOI starter kit, NZVAPOR, e-liquid from NZVAPOR) commencing on Day 1 for 10 weeks after randomisation.

Adherence will be assessed by direct enquiry by research assistants at the 6 week call and when participants return to the clinic for dispensing further supplies they will be asked to bring their medication packs for checking by the pharmacist or research assistants.
Intervention code [1] 295951 0
Treatment: Drugs
Intervention code [2] 295952 0
Behaviour
Comparator / control treatment
Varenicline tartrate 0.5 mg and 1 mg tablets (Pfizer); taken orally twice daily following a 1-week up-titration: Days 1 – 3: 0.5 mg once daily; Days 4 – 7: 0.5 mg twice daily; Day 8 – Day 14: 1 mg twice daily; Day 15 (randomisation day) -end of week 10: 1 mg twice daily.

Behavioural support will be offered to participants in this group>
Control group
Active

Outcomes
Primary outcome [1] 299701 0
The proportion of participants that report continuous smoking abstinence verified by an exhaled breath carbon monoxide (CO) measure of <10 ppm.
Timepoint [1] 299701 0
24 weeks after randomisation
Secondary outcome [1] 327890 0
The proportion of participants that report 7-day point prevalence abstinence verified by an exhaled breath carbon monoxide (CO) measure of <10 ppm
Timepoint [1] 327890 0
24 weeks after randomisation
Secondary outcome [2] 327891 0
The proportion of participants that report 7 day point prevalence abstinence verified by an exhaled breath carbon monoxide (CO) measure of <10 ppm.
Timepoint [2] 327891 0
6 weeks after randomisation
Secondary outcome [3] 327892 0
The proportion of participants that report 7 day point prevalence abstinence verified by an exhaled breath carbon monoxide (CO) measure of <10 ppm.
Timepoint [3] 327892 0
12 weeks after randomisation
Secondary outcome [4] 327893 0
The proportion of participants that report continuous abstinence
Timepoint [4] 327893 0
6 weeks after randomisation
Secondary outcome [5] 327894 0
The proportion of participants that report continuous abstinence
Timepoint [5] 327894 0
12 weeks after randomisation
Secondary outcome [6] 327939 0
The proportion of participants that report adverse events (defined as any adverse health event whether or not it has a plausible association with the study products, such as nausea), as reported by participants when asked by research assistants, and their severity (mild, moderate or severe), frequency (single, intermittent or continuous), outcome (resolved, ongoing, death, unknown), relationship with the study medication (definitely, probably, possibly, not related)
Timepoint [6] 327939 0
6 weeks after randomisation
Secondary outcome [7] 327940 0
The proportion of participants that report adverse events (defined as any adverse health event whether or not it has a plausible association with the study products, such as nausea), as reported by participants when asked by research assistants, and their severity (mild, moderate or severe), frequency (single, intermittent or continuous), outcome (resolved, ongoing, death, unknown), relationship with the study medication (definitely, probably, possibly, not related)
Timepoint [7] 327940 0
12 weeks after randomisation
Secondary outcome [8] 327941 0
The proportion of participants that report adverse events (defined as any adverse health event whether or not it has a plausible association with the study products, such as nausea), as reported by participants when asked by research assistants, and their severity (mild, moderate or severe), frequency (single, intermittent or continuous), outcome (resolved, ongoing, death, unknown), relationship with the study medication (definitely, probably, possibly, not related)
Timepoint [8] 327941 0
24 weeks after randomisation

Eligibility
Key inclusion criteria
*currently live in the Auckland region
*are registered clients with Community Mental Health Services or Community Alcohol and Drug Services
*smoke cigarettes daily
*want to quit smoking
*are at least 18 years of age
*are able to provide written informed consent
*have access to a telephone (mobile and/or landline)
*are prepared to use varenicline alone or with e-cigarettes
*have tried to quit at least twice before with nicotine replacement therapy (NRT), and thus are eligible for special authority varenicline
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*are pregnant or breastfeeding.
*are current users of other smoking cessation medications.
*are enrolled in a smoking cessation programme or another cessation research study.
*have used an e-cigarette for more than one week in the last year for smoking cessation.
*have contraindications for varenicline or nicotine e-cigarettes.
*another person in their household is already in the trial.

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)
Central computer randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
There will be run in period of two weeks as participants titrate up varenicline to full strength during which time they are expected to quit or if not, cut down smoking. Those who quit or have cut down by at least half (compared with baseline) by the end of the two weeks are not followed up further. Only those who fail to cut down by at least 50% are randomised into one of the 2 arms.
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
This sample size of 338 (169 in each arm) anticipates a 30% loss-to-follow-up and will confer 80% power, 2-sided p=0.05 to detect an absolute difference of 15% between the varenicline plus e-cigarette group and varenicline alone group in 24 week carbon monoxide verified abstinence rates, with a predicted abstinence rate in the varenicline plus e-cigarette group of 30%.

All data analyses will be carried out on an intention-to-treat (ITT) basis in which participant outcome data are analysed according to the group to which they were allocated at randomisation. Simple incidence rates, relative risks, absolute risks and the 95% confidence intervals around these estimates will be obtained for all binary variables, and multiple logistic regression analysis adjusting for other variables simultaneously will also be conducted. Continuous data will be analysed using multiple linear regression modelling or non-parametric analysis. Standard sensitivity analyses will be undertaken including per protocol analysis. Cost analyses will include calculating the cost per quitter and the incremental cost effectiveness ratio and incremental cost utility ratio.

Recruitment
Recruitment status
Active, not 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 outside Australia
Country [1] 8252 0
New Zealand
State/province [1] 8252 0
Auckland

Funding & Sponsors
Funding source category [1] 294559 0
Government body
Name [1] 294559 0
Health Research Council
Address [1] 294559 0
Health Research Council of New Zealand, PO Box 5541, Wellesley St, Auckland 1141,
Country [1] 294559 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland
Address
Private Bag 92019, Victoria Street West, Auckland 1142
Country
New Zealand
Secondary sponsor category [1] 293427 0
None
Name [1] 293427 0
Address [1] 293427 0
Country [1] 293427 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295995 0
Health and Disability Ethics Committee, Southern
Ethics committee address [1] 295995 0
Ministry of Health
PO Box 5013, Wellington 6011
Ethics committee country [1] 295995 0
New Zealand
Date submitted for ethics approval [1] 295995 0
14/09/2016
Approval date [1] 295995 0
07/11/2016
Ethics approval number [1] 295995 0
16/STH/153

Summary
Brief summary
People with mental illnesses or alcohol and/or other drug addictions are a group that needs to quit smoking: smoking prevalence is high among this population. They also have a high burden of tobacco-related illness. Current cessation treatments adopt a ‘one size fits all’ approach, overlooking considerable between-person variation in response to medication: the one third of smokers who reduce the amount they smoke by at least 50% (‘responders’) during the first two weeks after starting varenicline or nicotine replacement treatment (NRT) are 2.5 times more likely to quit smoking than those who do not (‘non-responders’). Trials (total N=557) showed NRT non-responders without a dual diagnosis can experience quit rates at 6 months identical to NRT responders by switching to varenicline or adding bupropion to NRT. Combining varenicline with either bupropion or NRT increased quit rates over varenicline alone, whilst the efficacy of nicotine e-cigarettes may be enhanced when used in addition to varenicline. These approaches to treatment have neither been integrated nor trialed among people with a dual diagnosis who are varenicline non-responders (a group with great opportunity to benefit should such simple changes to the use of available treatments lead to improved cessation efficacy).
Aims : To determine whether adding a nicotine e-cigarette to varenicline plus behavioural support improves 6 month smoking cessation outcomes, relative to remaining on varenicline alone plus behavioural support, in people with a dual diagnosis who are varenicline non-responders.
Design: An open label, pragmatic 3 arm, randomised controlled trial with the study population adult (18 years and older) outpatients currently receiving treatment who want to stop smoking. Exclusion criteria: contra-indications to trial medications and uncontrolled dual diagnosis symptoms (assessed by case doctor). Interventions: Participants will be prescribed varenicline by their case doctor, and receive telephone behavioural support from smoking cessation specialists for 2 weeks; those reporting a reduction in baseline cigarettes smoked per day of >50% by day 14 will continue on varenicline with referral to local cessation services. Varenicline non-responders will be randomised to one of 2 treatment arms for 12 weeks: 1) varenicline + nicotine e-cigarette; 2) varenicline only. All participants will set a target quit date for 2 weeks later and receive 6 more support calls over the next 6 weeks; the primary outcome will be measured at 24 weeks after randomisation.
Trial website
www.https://status.nihi.auckland.ac.nz
Trial related presentations / publications
Bullen et al. The effectiveness and safety of combining
varenicline with nicotine e-cigarettes for
smoking cessation in people with mental
illnesses and addictions: study protocol for
a randomised-controlled trial. BMC Public Health (2018) 18:596
https://doi.org/10.1186/s12889-018-5351-7
Public notes

Contacts
Principal investigator
Name 69186 0
Prof Chris Bullen
Address 69186 0
National Institute for Health Innovation
School of Population Health
The University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
New Zealand
Country 69186 0
New Zealand
Phone 69186 0
+6493737599
Fax 69186 0
+6493731710
Email 69186 0
c.bullen@auckland.ac.nz
Contact person for public queries
Name 69187 0
Prof Chris Bullen
Address 69187 0
National Institute for Health Innovation
School of Population Health
The University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
New Zealand
Country 69187 0
New Zealand
Phone 69187 0
+64937373599
Fax 69187 0
+6493731710
Email 69187 0
c.bullen@auckland.ac.nz
Contact person for scientific queries
Name 69188 0
Prof Chris Bullen
Address 69188 0
National Institute for Health Innovation
School of Population Health
The University of Auckland
Private Bag 92019
Auckland Mail Centre
Auckland 1142
New Zealand
Country 69188 0
New Zealand
Phone 69188 0
+64937373599
Fax 69188 0
+6493731710
Email 69188 0
c.bullen@auckland.ac.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary