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Trial registered on ANZCTR


Registration number
ACTRN12618000408280
Ethics application status
Approved
Date submitted
27/02/2018
Date registered
21/03/2018
Date last updated
13/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Cessation and Relapse Prevention (CARP) Trial: Nicotine vaporisers compared to standard nicotine replacement therapy for smoking cessation among people with co-morbidities.
Scientific title
A pragmatic randomised partial crossover clinical trial of nicotine vaporisers added to standard care for smoking cessation and relapse prevention (CARP) among priority populations with comorbidities
Secondary ID [1] 294173 0
NHMRC Grant Number GNT1124264
Universal Trial Number (UTN)
U1111-1204-2681
Trial acronym
CARP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tobacco smoking dependence 306804 0
Condition category
Condition code
Mental Health 305914 305914 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ARM 1: Standard quit support in the form of referral to Quitline telephone smoking cessation counselling + Nicotine patches (15mg/16hr) delivered at baseline. Arm 1 participants will also receive at baseline a nicotine vaporiser intervention in the form of a refillable nicotine vaporiser device (2 x kits) + nicotine vaporising liquid (in high and low strength - high strength: nicotine 1.8% in Vegetable Glycerine and purified water; low strength: nicotine 0.6% in Vegetable Glycerine and purified water). One patch to be applied daily to skin for up to 84 days. The vaporiser with nicotine liquid is to be used as needed up to 3.5mL per day to treat withdrawal symptoms for up to 2 years (concurrently with patches for the first 84 days) to assist smoking cessation and relapse prevention. Participants start on high strength nicotine liquid and may decrease their dose to low strength to assist with dose reduction prior to stopping use of the vaporiser.

Arm 2: Standard quit support in the form of referral to Quitline telephone smoking cessation counselling + Nicotine patches (15mg/16hr) + participant’s choice of either nicotine gum or nicotine lozenges (up to 800 x 4mg pieces to be used up to 8 per day) delivered at baseline. Between 6-9 months post baseline - participants in Arm 2 who are smoking (either failed to quit or relapsed) will be offered the nicotine vaporiser intervention in the form of: refillable nicotine vaporiser (2 x kits) + nicotine vaporising liquid (in high and low strength - high strength: nicotine 1.8% in Vegetable Glycerine and purified water; low strength: nicotine 0.6% in Vegetable Glycerine and purified water) to make a second quit attempt. Participants start on high strength nicotine liquid and may decrease their dose to low strength to assist with dose reduction prior to stopping use of the vaporiser at the discretion of the participant. Participants will have until 2 years from baseline to use the vaporiser for smoking cessation and relapse prevention.

Use of the intervention will be monitored through self-report via surveys which will be administered online and by telephone.
Intervention code [1] 300465 0
Treatment: Drugs
Intervention code [2] 300466 0
Treatment: Devices
Comparator / control treatment
ARM 2: At Baseline - referral to Quitline telephone smoking cessation counselling + nicotine patches (15mg/16hr) + short-acting nicotine replacement product (participant's choice of either nicotine gum 4mg or nicotine lozenge 4mg). One patch to be applied daily to skin for up to 84 days. The nicotine gum or lozenge is to be used as needed up to 8 per day to treat withdrawal symptoms (concurrently with patches for the first 84 days).
Control group
Active

Outcomes
Primary outcome [1] 304956 0
Continuous abstinence from smoking from weeks 12 to 26 assessed at 26 weeks from baseline via self report. Abstinence is assessed through study specific survey questions in Module CS Combustible Smoking Questions administered through through electronic survey or structured telephone interview. Participants that self-report abstinence from smoking will be asked for a urine specimen for bioconfirmation. Urine specimens will be batch tested for anabasine and cotinine at 6,12 and 21 month time points from baseline.
Timepoint [1] 304956 0
Week 26 from baseline.
Secondary outcome [1] 343721 0
Continuous abstinence from smoking from weeks 12 to 52 assessed at week 52 from baseline.

Abstinence is assessed through study specific survey questions in Module CS Combustible Smoking Questions – administered through electronic survey or structured telephone interview. Participants that self-report abstinence from smoking will be asked for a urine specimen for bioconfirmation. Urine specimens will be batch tested for anabasine and cotinine at 6,12 and 21 month time points.
Timepoint [1] 343721 0
Week 52 from baseline.
Secondary outcome [2] 343722 0
Continuous abstinence from smoking from weeks 12 to 104 assessed by self-report at week 104 from baseline.

Abstinence is assessed through study specific survey questions in Module CS Combustible Smoking Questions – administered through electronic survey or structured telephone interview. Participants that self-report abstinence from smoking will be asked for a urine specimen for bioconfirmation. Urine specimens will be batch tested for anabasine and cotinine at 6,12 and 21 month time points.
Timepoint [2] 343722 0
Week 104 from baseline.
Secondary outcome [3] 343723 0
Continuous abstinence from smoking from weeks 40 to 52 assessed by self-report at 52 weeks from baseline.

Abstinence is assessed through study specific survey questions in Module CS Combustible Smoking Questions – administered through electronic survey or structured telephone interview. Participants that self-report abstinence from smoking will be asked for a urine specimen for bioconfirmation. Urine specimens will be batch tested for anabasine and cotinine at 6,12 and 21 month time points.
Timepoint [3] 343723 0
Week 52 from baseline
Secondary outcome [4] 343724 0
Continuous abstinence from smoking from weeks 92 to 104 assessed by self-report at 104 weeks from baseline.

Abstinence is assessed through study specific survey questions in Module CS Combustible Smoking Questions – administered through electronic survey or structured telephone interview. Participants that self-report abstinence from smoking will be asked for a urine specimen for bioconfirmation. Urine specimens will be batch tested for anabasine and cotinine at 6, 12 and 21 month time points.
Timepoint [4] 343724 0
Week 104 from baseline.
Secondary outcome [5] 344287 0
Number of adverse events measured by self report at 12 weeks and 26 weeks from baseline. At conclusion of each survey participants will be asked about any adverse events they have experienced and these are recorded and trial investigators notified per adverse event reporting protocol. Participants will be encouraged to spontaneously report any health issues or unusual symptoms via the website. Once a participant is enrolled into the study, they have access to the participant lounge within the trial website. Within the lounge an option is provided to notify investigators of any health occurrence. This will trigger the clinical trial staff to contact the participant to confirm details.

Examples of previously documented adverse effects (McRobbie, Bullen et al. 2014, Hartmann-Boyce, McRobbie et al. 2016) include cough, dry mouth, throat irritation, indigestion, gas, diarrhoea, shortness of breath, irregular heart beat, hiccups, dizziness, taste disturbance, headache, and nausea.
Timepoint [5] 344287 0
12 weeks and 26 weeks from baseline

Eligibility
Key inclusion criteria
1) Diagnosed with or receiving treatment for a priority health conditions in the past 12 months;
2) Aged 18+ years;
3) Currently smoke 10+ cigarettes per day;
4) Has capacity to consent, able to understand participant materials and follow study instructions and comply with study procedures (e.g. sufficient English language ability, able to operate the vaporiser device);
5) Willing to make a quit attempt at baseline according to randomised condition (Condition A to make quit attempt with nicotine vaporiser; Condition B to make quit attempt without nicotine vaporiser);
6) Has a referral to Quitline counselling and smoking cessation support program (standard care) but has not commenced quit attempt (Note: Quitline referral can occur at time of study enrolment).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Already commenced quit attempt (i.e. post quit day) at time of enrolment into trial or currently enrolled in another smoking cessation clinical trial or using varenicline or bupropion or used a nicotine vaporiser product in the last 30 days. NOTE: Use of nicotine replacement products not supplied in the trial (e.g. as part of quitline support) is not an exclusion criteria.
2) Currently pregnant and/or breast-feeding or an intention to be during trial participation period;
i) A urinary pregnancy test will be required where pregnancy is suspected;
ii) Participants will be advised appropriate contraception should be used to avoid pregnancy during the trial with on-going contraception options discussed;
3) Has experienced cardiac related chest pain, or another cardiovascular event or procedure in the last month such as heart attack, stroke, insertion of stent, bypass surgery;
4) Hospitalised for a mental health condition in the last 30 days;
5) Currently being treated with oxygen therapy;
6) Diagnosed terminal illness (such as cancer) or debilitating condition that will limit ability to fully participate as determined by pre-registration responses from participant or opinion of enrolling clinician.

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 determined by pre-determined random sequence loaded into a central database. Enrolment occurs at recruitment sites via an internet interface - submission of the enrolment form returns the allocated condition from the database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Partial crossover. Conditions A and B receive different interventions during the same time span for the first 6 months of the study. Condition B is then offered the nicotine vaporiser intervention if they are currently smoking between 6-9 months post baseline for a second quit attempt.
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
For testing the 6 month primary hypothesis, we assume 30% attrition, a 10% quit rate in Condition A, and a 4% quit rate in Condition B. A total of N = 405 recruits per condition (n=810 total) will provide 80% power at p=0.05 level to detect =6% difference between conditions A & B.

Data will be analysed using descriptive statistics and logistic regression. We will compare Conditions A and B for primary and secondary outcomes using independent sample t-tests (continuous) and chi-square tests (categorical) and use generalised linear mixed models to take account of demographic variables, including co-morbidities. We will report the extent and nature of missing data and employ multiple imputation where appropriate.

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)
ACT,NSW,QLD,SA,VIC

Funding & Sponsors
Funding source category [1] 298807 0
Government body
Name [1] 298807 0
National Health and Medical Research Council
Address [1] 298807 0
16 Marcus Clarke St
Canberra ACT 2601
Country [1] 298807 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland
Brisbane QLD 4072 Australia
Country
Australia
Secondary sponsor category [1] 297998 0
None
Name [1] 297998 0
Address [1] 297998 0
Country [1] 297998 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299753 0
The Prince Charles Hospital Human Research and Ethics Committee
Ethics committee address [1] 299753 0
Building 14
The Prince Charles Hospital
Rode Road
CHERMSIDE QLD 4032
Ethics committee country [1] 299753 0
Australia
Date submitted for ethics approval [1] 299753 0
09/11/2017
Approval date [1] 299753 0
07/02/2018
Ethics approval number [1] 299753 0
HREC/17/QPCH/422

Summary
Brief summary
This pragmatic, open-label randomised partial cross-over trial aims to evaluate if adding a nicotine maintenance intervention (a nicotine vaporiser, 3 months of refill fluid at no cost and additional refill fluid at cost until final follow-up at 24 months) to standard quit support intervention (a 3 month course of cessation pharmacotherapy at no cost, self-help materials and active referral to Quitline) improves quit rates for people with priority medical conditions and whether offering both interventions concurrently (Condition A: both interventions used started at the same time) is more effective and cost-effective than offering the interventions sequentially (Condition B: only standard quit support offered at baseline and nicotine maintenance intervention only offered to those who are not abstinent at 6 months).
Hypotheses:
Condition A will have a higher rate of 3 months continuous abstinence compared to Condition B at 6 months (H1) and 12 months (H2) and lower relapse rates at 6, 12 and 24 months (H3).
Condition A will be more cost-effective than Condition B at 6 months (H4) and 12 months (H5).
Outcomes/significance:
Smoking is a leading cause of preventable death for people with priority medical conditions due to their high smoking prevalence, greater vulnerability to tobacco-related disease and low quit rates with current cessation therapies. Our study will provide evidence on the effectiveness, safety and cost-effectiveness of offering nicotine maintenance in addition to standard cessation treatment to people living with comorbidities.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81466 0
A/Prof Coral Gartner
Address 81466 0
School of Public Health,
The University of Queensland
The Public Health Building,
Corner of Herston Road and Wyndham St
Herston QLD 4006 Australia
Country 81466 0
Australia
Phone 81466 0
+61 7 33465478
Fax 81466 0
+61 7 3365 5442
Email 81466 0
c.gartner@uq.edu.au
Contact person for public queries
Name 81467 0
Dr Malcolm Brinn
Address 81467 0
School of Public Health,
The University of Queensland
The Public Health Building,
Corner of Herston Road and Wyndham St
Herston QLD 4006 Australia
Country 81467 0
Australia
Phone 81467 0
+61 7 3346 4689
Fax 81467 0
+61 7 3365 5442
Email 81467 0
m.brinn@uq.edu.au
Contact person for scientific queries
Name 81468 0
Dr Malcolm Brinn
Address 81468 0
School of Public Health,
The University of Queensland
The Public Health Building,
Corner of Herston Road and Wyndham St
Herston QLD 4006 Australia
Country 81468 0
Australia
Phone 81468 0
+61 7 3346 4689
Fax 81468 0
+61 7 3365 5442
Email 81468 0
m.brinn@uq.edu.au

No information has been provided regarding IPD availability
Summary results
No Results