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Trial registered on ANZCTR


Trial ID
ACTRN12617000232336p
Ethics application status
Submitted, not yet approved
Date submitted
2/02/2017
Date registered
14/02/2017
Date last updated
20/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomized study in Maori / Pacific Islander smokers comparing exposure to selected harmful and potentially harmful constituents (HPHCs) of those switching to the iQOS device, continuing with conventional cigarette smoking and smoking abstinence.
Scientific title
A randomized, controlled, open-label, 3-arm parallel group, single-center study to demonstrate exposure to selected HPHCs and to characterise the subjective effects related to smoking in Maori / Pacific Islander smokers switching to the iQOS, as compared to continuing to use conventional cigarettes and smoking abstinence (HARPE)
Secondary ID [1] 291047 0
None
Universal Trial Number (UTN)
Trial acronym
HArm Reduction Product Evaluation Study (HARPE Study)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Smoking 301838 0
Condition category
Condition code
Public Health 301517 301517 0 0
Other public health
Mental Health 301580 301580 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised into 3 different arms:

iQOS Arm: Participants randomised to this arm will be educated by the researcher for approximately 20 minutes (e.g. face-to-face) on the use of iQOS device and the participant tobacco diary. Each participant will be provided with two iQOS devices and two packs of iQOS HeatSticks at Baseline. The participant may choose their preferred iQOS HeatStick flavour from any HeatStick flavours commercially available in New Zealand. Use manual will be provided to the participants. The iQOS device can be used as often as the participant desires and conventional cigarette smoking is allowed occasionally. All iQOS device and conventional cigarette use is to be logged in the diary. The duration of the intervention is 8 weeks.

Conventional Cigarette Arm: Participants randomised to the conventional cigarette arm will not be supplied with conventional cigarettes or pouch tobacco. These participants will continue to smoke conventional cigarette or pouch tobacco of their preferred brand. Participants are not allowed to smoke during study assessments (including questionnaire completion). No restrictions on the frequency of conventional cigarette smoking apply. At Week 8, participants will be asked to take part in the "Treatment Extension" period on the use of the iQOS device as per the iQOS arm. All smoking activity will need to be logged in the tobacco diary.

Smoking Abstinence Arm: Participants will be confined from Baseline through to Day 3 and will be supplied with nicotine patches plus nicotine lozenges or nicotine gum. The nicotine replacement therapy is to be used according to the product guidelines. At the end of Week 8, the participants in this arm will not be offered to switch to other trial arms. The researcher will provide further guidance on continuing smoking cessation as appropriate.

An iQOS device is comprised of three main components - HeatStick, holder and charger. The iQOS HeatStick is inserted into the iQOS holder to pre-heat the device. Thereafter, the aerosol generated by the heating process is inhaled by placing the lips on the mouthpiece filter and drawing air through the iQOS HeatStick. During use, the iQOS HeatStick is heated according to a controlled temperature profile within the iQOS holder. The temperature is less than 350 degrees Celsius. At this temperature, the tobacco of the iQOS HeatStick is heated without combustion.

The iQOS HeatStick is similar in basic design to a conventional cigarette, but is shorter, contains less tobacco material and has an additional filter section. The participants will be educated by the researcher on the day of randomisation. All manuals will be provided as well as an access to an online video tutorials.

Adherence of participants to their treatment arms will be monitored through their tobacco diary.
Intervention code [1] 297035 0
Lifestyle
Intervention code [2] 297036 0
Behaviour
Intervention code [3] 297092 0
Treatment: Devices
Comparator / control treatment
The control treatment is the conventional cigarette smoking inhalation and the smoking abstinence.

The use of iQOS device and its effects on HPHC levels will be compared to the control groups mentioned above.
Control group
Active

Outcomes
Primary outcome [1] 300927 0
To evaluate the levels of 5 selected biomarkers of exposure to HPHCs in Maori / Pacific Islander smokers switching from conventional cigarettes to iQOS as compared to Maori / Pacific Islander smokers continuing to smoke conventional cigarettes and smoking abstinence after 8 weeks of use. The biomarkers that will be assessed from urine samples collected over 8 weeks are S-PMA (Benzene), MHBMA (1,3-Butadiene), total NNAL and cotinine levels and quantitative breath CO testing.

Timepoint [1] 300927 0
After 8 weeks of iQOS device use.
Secondary outcome [1] 331224 0
To evaluate the levels of 5 selected biomarkers of exposure to HPHCs in Maori / Pacific Islander smokers switching from conventional cigarettes to iQOS as compared to Maori / Pacific Islander smokers continuing to smoke conventional cigarettes and smoking abstinence after 16 weeks of use. The biomarkers that will be assessed from urine samples collected over 16 weeks are S-PMA (Benzene), MHBMA (1,3-Butadiene), total NNAL and cotinine levels and quantitative breath CO testing.
Timepoint [1] 331224 0
After 16 weeks of iQOS device use.
Secondary outcome [2] 331225 0
To evaluate the nicotine dependence in an ambulatory setting in Maori / Pacific Islander smokers switching from conventional cigarettes to iQOS as compared to Maori / Pacific Islander smokers continuing to smoke conventional cigarettes. The Fagerstorm Test for Nicotine Dependence (FTND) will be used to assess nicotine dependence.
Timepoint [2] 331225 0
16 weeks post commencement of iQOS device use
Secondary outcome [3] 331226 0
To characterise the composite subjective effects related to smoking in Maori / Pacific Islander smokers switching from conventional cigarettes to iQOS as compared to Maori / Pacific Islander smokers continuing to smoke conventional cigarettes and smoking abstinence.

The composite subjective effects of using the iQOS device as compared to conventional cigarettes will be assessed through the Modified Cigarette Evaluation Questionnaire (mCEQ, Cappelleri et al., 2007), Questionnaire of Smoking Urges (QSU-brief, Cox et al., 2001), Minnesota Nicotine Withdrawal Scale (MNWS, Toll et al., 2007) and Device Rating Questionnaire (modified from Bullen et al., 2010). Subjective effects of using the iQOS as compared to smoking abstinence will be assessed through the QSU brief and MNWS.
Timepoint [3] 331226 0
After 16 weeks of intervention

Eligibility
Key inclusion criteria
1. Willing and able to comply with study procedures and provide written informed consent;
2. Male or female, 19 to 75 years of age, inclusive;
3. Participant ‘self-identifies’ as of Maori or Pacific Island ethnicity;
4. Participant has smoked consecutively for at least 1 year prior to the Baseline visit;
5. Participant smokes at least 10 commercially available conventional cigarettes or pouch tobacco cigarettes per day (no brand restrictions) for the last 4 weeks prior to both the Screening visit and Baseline visit;
6. Female participants of childbearing potential and male participants with partners of childbearing potential must agree to use adequate methods of contraception during the study.
Minimum age
19 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participant plans to quit smoking within 8 weeks from the Baseline visit;
2. Unwilling to accept interruption to conventional cigarette or pouch tobacco cigarette smoking for up to 8 weeks when being randomized to the iQOS arm or smoking abstinence arm;
3. Use of nicotine replacement therapy (i.e. nicotine patches, gum and/or lozenges) within 4 weeks prior to both the Screening visit and Baseline visit;
4. Female participants who are pregnant, breastfeeding or plan to become pregnant within the next 6 months;
5. Participant is employed by the tobacco industry or is a first degree relative of a person employed by the tobacco industry;
6. Participant is, in the opinion of the investigator, considered to be an unsuitable candidate for the study for any reason.

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 not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation - computerised sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
For each of the 5 selected biomarkers of exposure to HPHCs, the null hypothesis shall be that the mean exposure shall be equal for the iQOS ‘treatment’ group, the conventional cigarette ‘treatment’ group, and the smoking abstinence ‘treatment’ group; the alternative hypothesis is that mean exposure is not equal for at least 1 pair of goups. For QSU-brief, and MNSW the null hypothesis shall be that the mean of the iQOS ‘treatment’ group is equal to the mean of the conventional cigarette ‘treatment’ group, and to the mean of the smoking abstinence ‘treatment’ group; the alternative hypothesis is that the means are not equal for at least 1 pair of groups.

For mCEQ, FTND, DRQ the null hypothesis shall be that the mean of the iQOS ‘treatment’ group is equal to the mean of the conventional cigarette ‘treatment’ group; the alternative hypothesis is that the means are not equal.

The change from baseline in exposure to the 5 selected biomarkers, mCEQ, QSU-brief, FTND, DRQ and other secondary or exploratory variables shall be analysed with Analysis of Covariance (ANCOVA) with the baseline value as the covariate. The assumptions of the ANCOVA such as Normality of the residuals, and constant variance shall be assessed with residual versus fitted plots and Normal probability plots. If necessary rectifying transformations will be applied, or the data may be analysed with the non-parametric Kruskal-Wallis test for greater than 2 independent groups and the Mann-Whitney test for 2 independent groups for pairwise comparisons. The Hochberg procedure will be used to control the probability of a Type 1 error.

The endpoints will be assessed from the data collected from all participants who completed at least the first 8 weeks of the study, for whom baseline data are available and were compliant with the study procedures.

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 outside Australia
Country [1] 8613 0
New Zealand
State/province [1] 8613 0

Funding & Sponsors
Funding source category [1] 295488 0
Commercial sector/Industry
Name [1] 295488 0
Optimal Clinical Trials
Address [1] 295488 0
Level 2
97 Grafton Rd
Grafton
Auckland 1010
Country [1] 295488 0
New Zealand
Primary sponsor type
Commercial sector/Industry
Name
Optimal Clinical Trials
Address
Level 2
97 Grafton Rd
Grafton
Auckland 1010
Country
New Zealand
Secondary sponsor category [1] 294308 0
None
Name [1] 294308 0
Address [1] 294308 0
Country [1] 294308 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 296816 0
Health And Disability Ethics Committee
Ethics committee address [1] 296816 0
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 296816 0
New Zealand
Date submitted for ethics approval [1] 296816 0
02/02/2017
Approval date [1] 296816 0
Ethics approval number [1] 296816 0

Summary
Brief summary
iQOS is a novel device which heats a specifically designed tobacco stick, known as a HeatStick, rather than burning the tobacco. In this way it offers smokers an alternative to conventional cigarettes. iQOS has been approved by the New Zealand regulatory authorities and is currently available on the market. The purpose of this study is to find out how the levels of harmful and potentially harmful constituents (HPHCs) in Maori/Pacific Islander smokers is different depending on if they smoke conventional cigarettes, use the iQOS or abstain from smoking. The study also aims to characterize the subjective effects of smoking in the Maori/Pacific Islander population when switching from conventional smoking to iQOS as compared to continuing with conventional smoking and smoking abstinence.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72114 0
Dr Barnaby Montgomery
Address 72114 0
Optimal Clinical Trials
Level 2
97 Grafton Rd
Grafton
Auckland 1010
Country 72114 0
New Zealand
Phone 72114 0
+64 9 303 4987
Fax 72114 0
Email 72114 0
barney@optimalclinicaltrials.com
Contact person for public queries
Name 72115 0
Ms Francisca Reed
Address 72115 0
Optimal Clinical Trials
-Level 2
97 Grafton Rd
Grafton
Auckland 1010
Country 72115 0
New Zealand
Phone 72115 0
+64 9 303 4987
Fax 72115 0
Email 72115 0
francisca@optimalclinicaltrials.com
Contact person for scientific queries
Name 72116 0
Dr Barnaby Montgomery
Address 72116 0
Optimal Clinical Trials
Level 2
97 Grafton Rd
Grafton
Auckland 1010
Country 72116 0
New Zealand
Phone 72116 0
+64 9 303 4987
Fax 72116 0
Email 72116 0
barney@optimalclinicaltrials.com