ACTRN12618000408280.

Study name	A pragmatic randomized partial cross‐over clinical trial of nicotine vaporizers added to standard care for smoking cessation and relapse prevention (CARP) among priority populations with comorbidities
Methods	Randomized controlled trial Setting: Australia Recruitment: Not stated
Participants	Target sample size: 810 Inclusion criteria: Diagnosed with or receiving treatment for a priority health conditions in the past 12 months Aged 18+ years Currently smoke 10+ cigarettes per day 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) Willing to make a quit attempt at baseline according to randomized condition (Condition A to make quit attempt with nicotine vaporizer; Condition B to make quit attempt without nicotine vaporizer) Has a referral to Quitline counseling and smoking cessation support program (standard care) but has not begun quit attempt (Note: Quitline referral can occur at time of study enrolment) Exclusion criteria: Already begun 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 vaporizer 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 criterion Currently pregnant or breast‐feeding or an intention to be during trial participation period; A urinary pregnancy test will be required where pregnancy is suspected Participants will be advised appropriate contraception should be used to avoid pregnancy during the trial with ongoing contraception options discussed 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 Hospitalized for a mental health condition in the last 30 days Currently being treated with oxygen therapy Diagnosed terminal illness (such as cancer) or debilitating condition that will limit ability to fully participate as determined by preregistration responses from participant or opinion of enrolling clinician
Interventions	Arm 1) Referral to Quitline telephone smoking cessation counseling + Nicotine patches (15 mg/16‐hr) delivered at baseline + refillable nicotine vaporizer 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). 1 patch to be applied daily to skin for up to 84 days. The vaporizer with nicotine liquid is to be used as needed up to 3.5 mL 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 vaporizer. Arm 2) Referral to Quitline telephone smoking cessation counseling + Nicotine patches (15 mg/16‐hr) + participant’s choice of either nicotine gum or nicotine lozenges (up to 800 x 4 mg 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: refillable nicotine vaporizer (2 x kits) + nicotine vaporizing 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 vaporizer at the discretion of the participant. Participants will have until 2 years from baseline to use the vaporizer for smoking cessation and relapse prevention
Outcomes	Primary outcomes: Continuous abstinence from smoking from weeks 12 to 26 assessed at 26 weeks from baseline by self‐report. 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 Secondary outcomes: Continuous abstinence from smoking from weeks 12 to 52, assessed at week 52 from baseline Continuous abstinence from smoking from weeks 12 to 104, assessed by self‐report at week 104 from baseline Continuous abstinence from smoking from weeks 40 to 52, assessed by self‐report at 52 weeks from baseline Continuous abstinence from smoking from weeks 92 to 104, assessed by self‐report at 104 weeks from baseline Number of adverse events measured by self‐report at 12 weeks and 26 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
Starting date	5 June 2018
Contact information	Malcolm Brinn, m.brinn@uq.edu.au Coral Gartner, c.gartner@uq.edu.au
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