Heated Tobacco Products vs Electronic Cigarettes
Condition: Smoking, Cigarette
Study type: Interventional

Summary: 
      This is a 12-weeks, open label, non-inferiority trial comparing HTPs vs ECs in terms of
      efficacy, adoption rate and acceptability, tolerability, and tobacco harm reduction in 220
      healthy smokers, not motivated to quit, randomized (1:1) to switch to one of these products.
      The duration of the study, from the enrollment to the study close out for all the patients at
      week 24 (follow-up), will be approximately 12 months. Enrollment period will last about 6
      months with the support of a multi-channel advertising method. This will include
      location-based advertising on social networks, advertising in local media, information days
      organized within the city.
    

Detailed description: 
      Before the baseline visit, a face to face screening (V0) for pre-eligibility checks will be
      conducted. Subjects will be asked to practice with the step test for 10-15 minand will be
      instructed how to collect and store their morning urine before bringing it to the hospital on
      their Baseline visit (V1). This study will consist of a baseline visit (V1) and 6 follow-up
      study visits (V2-V7). At baseline (V1), participants will be randomized in two separate study
      groups. The randomization sequence will be computer generated by using blocks size of 5, with
      an allocation ratio of 1:1 for each of the study products (IQOS, JustFog-EC). Subjects will
      use and familiarize with their allocated product, as per randomization. They will be trained
      and counseled on the use of their allocated study product; oral explanation and practical
      demonstration will be followed by product trial during which participants will also have the
      option to try and choose their preferred flavour (either from a selection of 3 e-liquids or 3
      tobacco sticks, depending on the allocated arm). Participants randomized in the IQOS arm will
      receive one iQOS kit and a full 1 week supply of tobacco sticks of their choice (they will
      receive a number of tobacco sticks/day corresponding to the number of cigarettes smoked at
      baseline); those randomized in the JustFog-EC arm of the study will receive one JustFog
      Starter Kit and a full 1 week supply of e-liquids of their choice (they will receive 4, 10
      mls refill containers).Free products will be supplied at each subsequent visit throughout the
      study. No supply of tobacco stick or e-liquid will be given at week-12, but users will be
      offered to keep using their products to minimize the risk of relapsing back to cigarette
      smoking. A prospective evaluation of cigarette consumption, adoption rates, acceptability and
      tolerability will be recorded throughout the study.

      Visit 2 (V2):This will be scheduled 1 week after V1 (with a tolerance of +/- 3 days).
      Cigarette/day, eCO, AEs, BP, HR will be measured and product use recorded. Full 1 week supply
      of the chosen product will be provided.

      Visit 3 (V3):This will be scheduled 2 weeks after V1 (with a tolerance of +/- 3 days).
      Cigarette/day, eCO, AEs, BP, HR will be measured and product use recorded. Participants will
      be instructed on how to collect and store their second urine sample before bringing it to the
      hospital at V4. Full 2 weeks supply of the chosen product will be provided.

      Visit 4 (V4):This will be scheduled 4 weeks after V1 (with a tolerance of +/- 3 days).
      Cigarette/day, eCO, AEs, BP, HR will be measured, questionnaires completed and product use
      recorded. Step test will be carried out. Second urine sample will be collected, aliquotted
      and stored. Full 4 weeks supply of the chosen product will be provided.

      Visit 5 (V5):This will be scheduled 8 weeks after V1 (with a tolerance of +/- 7 days).
      Cigarette/day, eCO, AEs, BP, HR will be measured, questionnaires completed and product use
      recorded. Full 4 weeks supply of the chosen product will be provided.

      Visit 6 (V6):This will be scheduled 12 weeks after V1 (with a tolerance of +/- 7 days).
      Cigarette/day, eCO, AEs, BP, HR, weight, height will be measured, questionnaires completed
      and product use recorded. Step test will be carried out. No more products will be dispensed.

      Follow-up Visit (V7):This final visit will be scheduled 24 weeks after V1 (with a tolerance
      of +/- 7 days)to review product usage and smoking behavior under naturalistic condition of
      use. Cigarette/day, eCO, AEs, BP, HR, weight, height will be measured, questionnaires
      completed and product use recorded. Step test will be carried out.

      Data will be recorded from every subject on an electronic CRF, provided by a CRO, GCP
      compliant, 21 CFR Part 11 FDA compliant, listed in AIFA list of operating CRO. Urine samples
      will be collected at baseline and wk 4, and sent to an external laboratory for analytical
      assessment of selected Biomarkers of Exposure (BoE).

      The study will be conducted at the University of Catania, Catania, Italy.

      Participants Healthy smokers, not motivated to quit, will be randomized in two intervention
      groups in a 1:1 ratio to compare HTPs vs ECs in terms of reductions in cigarette consumption,
      adoption rate and acceptability, tolerability, and tobacco harm reduction. Sample size
      determination (better detailed below, in the relevant section) for no-inferiority testing is
      based on the assumptions that 1) expected quit rates based on most recent EC literature is
      about 20-25% and 2) that differences in quit rates between products under investigation
      should not exceed 10-15% (as per non-inferiority definition). According to these hypotheses
      the required number of participants per study arm is 104. Hence investigators intend to
      include 220 participants, 110 per group.

      Study Products Tested

        -  Heated Tobacco Product (HTP):Investigators will use a HTP that does not involve
           combustion, generating a nicotine-containing aerosol. At the time of writing, IQOS is
           the only HTP available on the Italian market. IQOS is composed by: 1) a tobacco stick -
           a novel patent-pending tobacco product with unique processed tobacco made from tobacco
           powder; 2) an electronic holder into which the tobacco stick is inserted and which heats
           the tobacco by means of an electronically controlled heating blade; 3) a charger that is
           used to recharge the holder after each use.

        -  Investigators will use the three types of tobacco sticks specifically designed for
           IQOS(named HEETS) that are currently for sale in the Italian market: Heets Amber, Heets
           Yellow, and Heets Turquoise. These products are compliant to the EU Tobacco Product
           Directive.

        -  Electronic Cigarette (EC):JustFog Q16 Starter Kit and three types of e-liquid flavours,
           Puff Riserva Country 16 mg, Puff Riserva Toscana 16 mg, and Puff Artic 16 mg (2
           tobacco-flavours and one menthol flavour), were chosen for the study.

        -  Products were selected by an Italian expert panel of 3 e-liquid producers and 3 vaping
           product distributors, moderated by the editor of a popular e-cigarette blog. Experts
           convened in Verona (Italy) during a major vaping expo event. Through consensus, the
           expert panel provided specific recommendation on the device(JustFog Q16 Starter Kit is
           one of the most popular e-cigarette device in Italy due to its good performance and
           quality, affordable price, and user friendliness especially for beginners) and the
           choice of e-liquids that could best match the sensorial experience of the iQOS tobacco
           sticks to be used in a switching study and minimize the local irritant effects of
           excessive PG/VG ratio. These products are compliant to the EU Tobacco Product Directive.
    

Intervention name(s): IQOS; E-CIG
Intervention type(s): Device; Device
Intervention description(s): IQOS USE FOR 12 WEEKS; ELECTRONIC CIGARETTE FOR 12 WEEKS
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: smoking; harm reduction; electronic cigarette; heated tobacco product