<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03235505</url>
  </required_header>
  <id_info>
    <org_study_id>WI218780</org_study_id>
    <nct_id>NCT03235505</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of E-cigarettes for Smoking Cessation in Middle-aged Heavy Smokers</brief_title>
  <acronym>EFFECT</acronym>
  <official_title>Efficacy and Safety of E-cigarettes for Smoking Cessation in Middle-aged Heavy Smokers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oulu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lapland Central Hospital Rovaniemi Finland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oulu</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Abstract Rationale. Electronic cigarette use is increasing at an exponential rate in Finland&#xD;
      and internationally. The health consequences of vaporised aerosols in electronic cigarettes&#xD;
      are largely unknown especially in a long run. Still, very few studies are available on&#xD;
      quitting attempts with e-cigarettes as a smoking cessation tool compared to evidence based&#xD;
      cessation pharmacotherapy in adult smokers who want to quit.&#xD;
&#xD;
      Research Objective: To investigate effectiveness and safety of e-cigarettes for smoking&#xD;
      cessation in middle-aged smokers, and to compare the effectiveness of them to varenicline.&#xD;
      Our study provides new information of success in smoking cessation among heavy adult smokers&#xD;
      for clinicians.&#xD;
&#xD;
      Design: A double-blind, randomised, placebo-controlled clinical trial with the intervention&#xD;
      phase of 12 weeks and the observational phase up to 52 weeks. This is an investigator&#xD;
      initiated study.&#xD;
&#xD;
      Setting: Volunteer middle-aged daily smokers, who were recruited through newspaper&#xD;
      announcements. Some of the cohort subjects were re-recruited from our previous follow-up&#xD;
      study as many of them continued daily smoking during the whole follow-up period.&#xD;
&#xD;
      Participants: Targeted sample size of 450 adult heavy smokers, who want to quit smoking and&#xD;
      are willing to participate up to 52 weeks´ follow-up.&#xD;
&#xD;
      Intervention and procedures: Standardized self-reported questionnaires with detailed smoking&#xD;
      history with assessment of motivation to quit smoking, parameters of nicotine dependence,&#xD;
      symptoms will be included. Smoking status will be repeatedly reassessed during the study&#xD;
      visits, and self-reported smoking abstinence is verified with exhaled-carbon monoxide (CO)&#xD;
      assessment. All adverse side effects either of drugs or of e-cigarettes, and symptoms related&#xD;
      to the drugs or to withdrawal from smoking will be carefully reported.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study with three arms. Each arm has 12 weeks intervention and observation up to 12&#xD;
      months:&#xD;
&#xD;
      A.Nicotine containing e-cigarettes + placebo-pills + Motivational Interview (MI)&#xD;
&#xD;
      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml&#xD;
      /month refill containing 18mg/ml nicotine with cigarette taste for 12 weeks.&#xD;
&#xD;
      Participants are allowed to use ad libitum e-cigarettes during 12 weeks after they have&#xD;
      chosen the quit day during the 2nd follow-up week&#xD;
&#xD;
      Placebo -pills: starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on days&#xD;
      4.-5.Continuing weeks: 1mg twice daily up to 12 weeks&#xD;
&#xD;
      B.Nicotine-free e-cigarettes + varenicline + MI&#xD;
&#xD;
      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml&#xD;
      /month refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are&#xD;
      allowed to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day&#xD;
      during the 2nd follow-up week&#xD;
&#xD;
      Varenicline (Chantix®) Starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on&#xD;
      days 4.-5. Continuing weeks: 1mg twice daily up to 12 weeks&#xD;
&#xD;
      C.Placebo-varenicline + nicotine -free e-cigarettes + MI Placebo -pills : starting week:&#xD;
      0,5mg once daily on days 1.-3 and 0,5mg twice daily on days 4.-5.Continuing weeks: 1mg twice&#xD;
      daily up to 12 weeks&#xD;
&#xD;
      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ 6x 10ml /month&#xD;
      refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are allowed&#xD;
      to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day during the&#xD;
      2nd follow-up week&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2018</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Smoking cessation during the follow-up visit at week 26</measure>
    <time_frame>24 week</time_frame>
    <description>7-day point prevalence verified by exhaled-CO&lt;10ppm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Smoking cessation at any other study visit</measure>
    <time_frame>Baseline,1, 12 and 52 week</time_frame>
    <description>7-day point prevalence verified by exhaled-CO &lt; 10pp</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduce smoking at any study visit</measure>
    <time_frame>Baseline, 1,4 ,12,16, 26, 36 and 52 week</time_frame>
    <description>Prevalence of those who succeeded to decrease the number of daily cigarettes during the study</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">450</enrollment>
  <condition>Smoking Cessation</condition>
  <condition>Electronic Cigarette</condition>
  <arm_group>
    <arm_group_label>Nicotine containing e-cigarettes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nicotine-free e-cigarettes</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nicotine-free e-cigarettes + varenicline tartrate+ MI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Motivational Interview (MI)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo-varenicline + nicotine -free e-cigarettes + MI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine</intervention_name>
    <description>Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI)</description>
    <arm_group_label>Nicotine containing e-cigarettes</arm_group_label>
    <other_name>Innokin Endura T20S</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varenicline Tartrate</intervention_name>
    <description>Varenicline + Innokin Endura T20S electronic inhaler but without any nicotine content + MI</description>
    <arm_group_label>Nicotine-free e-cigarettes</arm_group_label>
    <other_name>Champix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Motivational Interview</intervention_name>
    <description>Placebo-varenicline + Innokin ENdura T20S electronic inhaler but without any nicotine content +MI</description>
    <arm_group_label>Motivational Interview (MI)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged between 25 to under 75 years&#xD;
&#xD;
          -  Has smoked over 10 years on a daily basis and being a current smoker with at least 10&#xD;
             cig/day for at least past 5 years&#xD;
&#xD;
          -  Good general health&#xD;
&#xD;
          -  Intent to quit smoking&#xD;
&#xD;
          -  Exhaled carbon monoxide level at least 15ppm at the baseline visit&#xD;
&#xD;
          -  Strong nicotine dependence defined by Fagerström Test for Nicotine Dependence (FTND) ≥&#xD;
             5 and by Heaviness of Smoking Index (HSI) ≥3&#xD;
&#xD;
          -  intent to quit smoking&#xD;
&#xD;
          -  prepared to follow the trial protocol and able to provide written consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or gestation or intend to get pregnant during the study follow-up&#xD;
&#xD;
          -  Use of smoking cessation pharmacotherapy or ECs during the past year&#xD;
&#xD;
          -  Attempt of smoking cessation by using of e-cigarettes during the past year&#xD;
&#xD;
          -  Any cancer (at least five healthy follow-up years after stopping the cancer therapy)&#xD;
&#xD;
          -  Instable (ischemic) vascular or heart disease&#xD;
&#xD;
          -  Recent myocardial infarction in the past three months&#xD;
&#xD;
          -  High blood pressure (systolic BP&gt; 140mmHg or diastolic 90mmHg at rest)&#xD;
&#xD;
          -  History of major psychiatric depression or other psychiatric conditions and daily use&#xD;
             of any psychiatric medicine&#xD;
&#xD;
          -  Current addiction of alcohol or misuse of substance&#xD;
&#xD;
          -  Inability to express himself/herself&#xD;
&#xD;
          -  Known allergy to any of the study medications&#xD;
&#xD;
          -  Severe allergy or poorly controlled asthma or other pulmonary disease&#xD;
&#xD;
          -  Epilepsy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tuula Toljamo, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laplnd Central Hospital Rovaniemi Finland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lapland Central Hospital</name>
      <address>
        <city>Rovaniemi</city>
        <zip>96440</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>June 2, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>February 15, 2023</last_update_submitted>
  <last_update_submitted_qc>February 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Oulu</investigator_affiliation>
    <investigator_full_name>Tuula Toljamo</investigator_full_name>
    <investigator_title>MD, PhD, Chief Chest Physician of Lapland Central Hospital</investigator_title>
  </responsible_party>
  <keyword>Smoking Cessation</keyword>
  <keyword>Electronic cigarette</keyword>
  <keyword>Adults</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
    <mesh_term>Varenicline</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03235505
org study id: WI218780
nct id: NCT03235505
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Abstract Rationale. Electronic cigarette use is increasing at an exponential rate in Finland
      and internationally. The health consequences of vaporised aerosols in electronic cigarettes
      are largely unknown especially in a long run. Still, very few studies are available on
      quitting attempts with e-cigarettes as a smoking cessation tool compared to evidence based
      cessation pharmacotherapy in adult smokers who want to quit.

      Research Objective: To investigate effectiveness and safety of e-cigarettes for smoking
      cessation in middle-aged smokers, and to compare the effectiveness of them to varenicline.
      Our study provides new information of success in smoking cessation among heavy adult smokers
      for clinicians.

      Design: A double-blind, randomised, placebo-controlled clinical trial with the intervention
      phase of 12 weeks and the observational phase up to 52 weeks. This is an investigator
      initiated study.

      Setting: Volunteer middle-aged daily smokers, who were recruited through newspaper
      announcements. Some of the cohort subjects were re-recruited from our previous follow-up
      study as many of them continued daily smoking during the whole follow-up period.

      Participants: Targeted sample size of 450 adult heavy smokers, who want to quit smoking and
      are willing to participate up to 52 weeks´ follow-up.

      Intervention and procedures: Standardized self-reported questionnaires with detailed smoking
      history with assessment of motivation to quit smoking, parameters of nicotine dependence,
      symptoms will be included. Smoking status will be repeatedly reassessed during the study
      visits, and self-reported smoking abstinence is verified with exhaled-carbon monoxide (CO)
      assessment. All adverse side effects either of drugs or of e-cigarettes, and symptoms related
      to the drugs or to withdrawal from smoking will be carefully reported.
This is a study with three arms. Each arm has 12 weeks intervention and observation up to 12
      months:

      A.Nicotine containing e-cigarettes + placebo-pills + Motivational Interview (MI)

      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml
      /month refill containing 18mg/ml nicotine with cigarette taste for 12 weeks.

      Participants are allowed to use ad libitum e-cigarettes during 12 weeks after they have
      chosen the quit day during the 2nd follow-up week

      Placebo -pills: starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on days
      4.-5.Continuing weeks: 1mg twice daily up to 12 weeks

      B.Nicotine-free e-cigarettes + varenicline + MI

      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ + 6x 10ml
      /month refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are
      allowed to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day
      during the 2nd follow-up week

      Varenicline (Chantix®) Starting week: 0,5mg once daily on days 1.-3 and 0,5mg twice daily on
      days 4.-5. Continuing weeks: 1mg twice daily up to 12 weeks

      C.Placebo-varenicline + nicotine -free e-cigarettes + MI Placebo -pills : starting week:
      0,5mg once daily on days 1.-3 and 0,5mg twice daily on days 4.-5.Continuing weeks: 1mg twice
      daily up to 12 weeks

      Innokin Endura T20S + USB cable with wall adapter via USB cable (output DC5V)+ 6x 10ml /month
      refill containing 0mg/ml nicotine with cigarette taste for 12 weeks Participants are allowed
      to use ad libitum e-cigarettes during 12 weeks after they have chosen the quit day during the
      2nd follow-up week
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Smoking cessation during the follow-up visit at week 26
time frame: 24 week
description: 7-day point prevalence verified by exhaled-CO<10ppm
measure: Smoking cessation at any other study visit
time frame: Baseline,1, 12 and 52 week
description: 7-day point prevalence verified by exhaled-CO < 10pp
measure: Reduce smoking at any study visit
time frame: Baseline, 1,4 ,12,16, 26, 36 and 52 week
description: Prevalence of those who succeeded to decrease the number of daily cigarettes during the study
arm group label: Nicotine containing e-cigarettes
arm group type: Experimental
description: Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI)
arm group label: Nicotine-free e-cigarettes
arm group type: Active Comparator
description: Nicotine-free e-cigarettes + varenicline tartrate+ MI
arm group label: Motivational Interview (MI)
arm group type: Placebo Comparator
description: Placebo-varenicline + nicotine -free e-cigarettes + MI
intervention type: Drug
intervention name: Nicotine
description: Nicotine containing e-cigarettes + placebo-varenicline + Motivational Interview (MI)
arm group label: Nicotine containing e-cigarettes
other name: Innokin Endura T20S
intervention type: Drug
intervention name: Varenicline Tartrate
description: Varenicline + Innokin Endura T20S electronic inhaler but without any nicotine content + MI
arm group label: Nicotine-free e-cigarettes
other name: Champix
intervention type: Behavioral
intervention name: Motivational Interview
description: Placebo-varenicline + Innokin ENdura T20S electronic inhaler but without any nicotine content +MI
arm group label: Motivational Interview (MI)
criteria: 
gender: All
minimum age: 25 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tuula Toljamo, PhD
role: Principal Investigator
affiliation: Laplnd Central Hospital Rovaniemi Finland
facility: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: University of Oulu
investigator full name: Tuula Toljamo
investigator title: MD, PhD, Chief Chest Physician of Lapland Central Hospital
mesh term: Nicotine
mesh term: Varenicline
sharing ipd: No