<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/NCT02195739</url>
  </required_header>
  <id_info>
    <org_study_id>E02311</org_study_id>
    <nct_id>NCT02195739</nct_id>
  </id_info>
  <brief_title>Nicotine Replacement Therapy and Cardiovascular Disease</brief_title>
  <official_title>A Retrospective, Real-life Evaluation of the Cardiovascular Disease Risk Associated With Exposure to Pharmacological Smoking Cessation Interventions in a Representative UK Primary Care Patient Population.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Research in Real-Life Ltd</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Research in Real-Life Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to compare the cardiovascular disease event rate in smokers&#xD;
      undertaking pharmacologically unaided smoking cessation attempts (the non-exposed group) with&#xD;
      the event rate in smokers attempting smoking cessation assisted by pharmacological&#xD;
      interventions - by nicotine replacement therapy (as any, or a combination, of: nasal spray,&#xD;
      transdermal patches, inhaler or gum and tablets) or other pharmacological smoking cessation&#xD;
      aids (e.g. bupropion [Zyban®] and varenicline [Champix®]) - in a representative UK primary&#xD;
      care population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Preliminary study data have indicated a possible increased cardiovascular disease risk in&#xD;
      patients exposed to nicotine replacement therapy compared with controls (i.e. non-nicotine&#xD;
      replacement therapy exposed patients) of a magnitude that could not reasonably be accounted&#xD;
      for by differences in the cardiovascular risk profile of the two patient groups. Further&#xD;
      in-depth studies in this area are warranted.&#xD;
&#xD;
      This retrospective study will compare the cardiovascular disease event risk in a group of&#xD;
      smokers undertaking pharmacologically unaided smoking cessation attempts with the event rate&#xD;
      in a group of smokers attempting smoking cessation assisted by pharmacological interventions&#xD;
      (any of nicotine replacement therapy, bupropion or varenicline) in a representative UK&#xD;
      primary care population.&#xD;
&#xD;
      There are three main types of pharmacological interventions currently available for smoking&#xD;
      cessation, each of which has demonstrated efficacy when used in conjunction with behavioural&#xD;
      support: nicotine replacement therapy, bupropion, and varenicline. Other medications,&#xD;
      especially nortryptiline and clonidine, are considered to be effective adjunct therapy in&#xD;
      smoking cessation, but they remain second-line options at this time.&#xD;
&#xD;
      Nicotine replacement therapy has been available since the 1980s and bupropion since 2000.&#xD;
      Either approach to cessation doubles the chance of achieving abstinence when compared with&#xD;
      unsupported quit attempts. After being granted its European licence in 2006, varenicline&#xD;
      joined the pharmacological smoking cessation armamentarium. It is the first drug developed&#xD;
      specifically for the treatment of tobacco dependence that contains no nicotine, and it&#xD;
      triples smokers' chances of quitting compared with unsupported quit attempts.&#xD;
&#xD;
      As the fore-runner, nicotine replacement therapy is the longest-standing of the existing&#xD;
      pharmacological smoking cessation interventions currently available. It aims to alleviate&#xD;
      nicotine withdrawal symptoms by substituting the nicotine attained through tobacco smoking&#xD;
      via alternative means (e.g. nasal sprays, inhalers, gum and tablets, transdermal patches).&#xD;
      The various nicotine replacement therapy products available have differing durations of&#xD;
      action and allow patients to tailor their nicotine intake according to their particular&#xD;
      needs.For example, patches can be used to substitute for background nicotine and gums or&#xD;
      tablets can be used to help satisfy urges.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>September 2013</start_date>
  <completion_date type="Anticipated">December 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Time to first coronary heart disease diagnosis</measure>
    <time_frame>4 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior coronary heart disease.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to first cerebrovascular disease diagnosis.</measure>
    <time_frame>4 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior cerebrovascular disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first coronary heart disease diagnosis</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior coronary heart disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to first cerebrovascular disease diagnosis</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior cerebrovascular disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Odds of recording one or more consultations for coronary heart disease or cerebrovascular disease</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using conditional logistic regression model. Recorded General Practice consultations or hospital attendances for coronary heart disease or cerebrovascular disease, including General Practice consultations, Accident &amp; Emergency attendance, out-patient department attendance or in-patient admissions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time for coronary heart disease-related death.</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time for cerebrovascular disease-related death.</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival time for all-cause mortality.</measure>
    <time_frame>52 weeks</time_frame>
    <description>Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Survival time for coronary heart disease-related death</measure>
    <time_frame>Any time after index smoking cessation attempt</time_frame>
    <description>Analysed using Cox's proportional hazards model.</description>
  </other_outcome>
  <other_outcome>
    <measure>Survival time for cerebrovascular disease-related death</measure>
    <time_frame>Any time after index smoking cessation attempt</time_frame>
    <description>Analysed using Cox's proportional hazards model.</description>
  </other_outcome>
  <other_outcome>
    <measure>Survival time for all-cause mortality</measure>
    <time_frame>Any time after index smoking cessation attempt</time_frame>
    <description>Analysed using Cox's proportional hazards model.</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">61050</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>Nicotine replacement therapy cohort</arm_group_label>
    <description>Cohort defined as patients in whom nicotine replacement therapy (in any preparation) was initiated at the index smoking cessation attempt as the first recorded smoking cessation intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Other smoking cessation therapy</arm_group_label>
    <description>Cohort defined as patients in whom other (non-nicotine replacement therapy) smoking cessation pharmacotherapy's were initiated at the index smoking cessation attempt (e.g. bupropion, varenicline) as the first recorded smoking cessation intervention</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Smoking cessation advice cohort</arm_group_label>
    <description>Cohort (control patients) defined as patients whose first recorded smoking cessation intervention involved smoking cessation advice leading to a quit attempt unassisted by pharmacological smoking cessation aids, at the index smoking cessation attempt.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        EXPOSED PATIENTS: include smokers with no recorded smoking cessation attempts using&#xD;
        pharmacological aids in the prior year, whose index smoking cessation attempt was assisted&#xD;
        by one of the following pharmacological interventions:&#xD;
&#xD;
        (i) nicotine replacement therapy as any, or a combination, of transdermal patches, nasal&#xD;
        spray, gum and tablets, inhaler.&#xD;
&#xD;
        (ii) Other (e.g. bupropion, varenicline).&#xD;
&#xD;
        NON-EXPOSED PATIENTS: include smokers with no recorded smoking cessation attempts using&#xD;
        pharmacological aids in the prior year, whose index smoking cessation attempt involved&#xD;
        receipt of smoking cessation advice that resulted in a quit attempt unaided by&#xD;
        pharmacological therapies.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The analysis will include an exposure group comprising smokers with no recorded&#xD;
             smoking cessation attempts using pharmacological aids in the prior year, whose first&#xD;
             recorded smoking cessation intervention was a cessation attempt assisted by either&#xD;
             nicotine replacement therapy (using any of, or a combination of products) or another&#xD;
             pharmacological smoking cessation intervention (e.g. bupropion, varenicline) at the&#xD;
             index date.&#xD;
&#xD;
        Patients must also meet the following inclusion criteria:&#xD;
&#xD;
          -  Aged: 18-75 years.&#xD;
&#xD;
          -  Have at least one year of up-to-standard baseline data as defined by Clinical Practice&#xD;
             Research Datalink (prior to the index smoking cessation attempt) and at least one year&#xD;
             of up-to-standard outcome data (following the index smoking cessation attempt) or&#xD;
             up-to-standard data up to the time of death if death occurred within the outcome&#xD;
             period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients will be excluded from the analysis if they:&#xD;
&#xD;
          -  Have had exposure to any nicotine replacement therapy or other pharmacological smoking&#xD;
             cessation interventions in the baseline period (year prior to the index smoking&#xD;
             cessation attempt), and/or&#xD;
&#xD;
          -  Switched between types of smoking cessation interventions (i.e. nicotine replacement&#xD;
             therapy to other pharmacological smoking cessation interventions or vice versa) during&#xD;
             the outcome period(s). Switching between different nicotine replacement therapy&#xD;
             products, or use of multiple nicotine replacement therapy products, will be&#xD;
             permissible and analysis may involve a comparison of outcomes relative to nicotine&#xD;
             exposure over the various outcome periods.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Price, Prof, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Aberdeen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research in Real Life Ltd</name>
      <address>
        <city>Cambridge</city>
        <zip>CB24 3BA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>http://www.euro.who.int/__data/assets/pdf_file/0005/68117/E89842.pdf</url>
    <description>World Health Organization (WHO). 2007. The European tobacco control report 2007 [online]</description>
  </link>
  <link>
    <url>http://www.deathsfromsmoking.net</url>
    <description>eto R, Lopez AD, Boreham J, et al. 2006. Mortality from smoking in developed countries 1950 - 2000 (2nd ed.) [online]</description>
  </link>
  <reference>
    <citation>Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence. Clinical practice guideline. Rockville (MD): US Department of Health and Human Services, Public Health Service, 2000</citation>
  </reference>
  <reference>
    <citation>West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Health Education Authority. Thorax. 2000 Dec;55(12):987-99. doi: 10.1136/thorax.55.12.987.</citation>
    <PMID>11083883</PMID>
  </reference>
  <reference>
    <citation>Le Foll B, George TP. Treatment of tobacco dependence: integrating recent progress into practice. CMAJ. 2007 Nov 20;177(11):1373-80. doi: 10.1503/cmaj.070627. Erratum In: CMAJ. 2008 Mar 11;178(6):732.</citation>
    <PMID>18025429</PMID>
  </reference>
  <reference>
    <citation>Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000146. doi: 10.1002/14651858.CD000146.pub3.</citation>
    <PMID>18253970</PMID>
  </reference>
  <reference>
    <citation>Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006103. doi: 10.1002/14651858.CD006103.pub2.</citation>
    <PMID>17253581</PMID>
  </reference>
  <reference>
    <citation>British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary. Version 56. London; BNF Group; 2008.</citation>
  </reference>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>May 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <last_update_submitted>September 30, 2014</last_update_submitted>
  <last_update_submitted_qc>September 30, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 1, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>smoking</keyword>
  <keyword>smoking cessation</keyword>
  <keyword>cardiovascular disease</keyword>
  <keyword>pharmacological intervention</keyword>
  <keyword>UK primary care population</keyword>
  <keyword>nicotine replacement therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <!-- 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/NCT02195739
org study id: E02311
nct id: NCT02195739
lead sponsor: 
has dmc: No
The aim of this study is to compare the cardiovascular disease event rate in smokers
      undertaking pharmacologically unaided smoking cessation attempts (the non-exposed group) with
      the event rate in smokers attempting smoking cessation assisted by pharmacological
      interventions - by nicotine replacement therapy (as any, or a combination, of: nasal spray,
      transdermal patches, inhaler or gum and tablets) or other pharmacological smoking cessation
      aids (e.g. bupropion [Zyban®] and varenicline [Champix®]) - in a representative UK primary
      care population.
Preliminary study data have indicated a possible increased cardiovascular disease risk in
      patients exposed to nicotine replacement therapy compared with controls (i.e. non-nicotine
      replacement therapy exposed patients) of a magnitude that could not reasonably be accounted
      for by differences in the cardiovascular risk profile of the two patient groups. Further
      in-depth studies in this area are warranted.

      This retrospective study will compare the cardiovascular disease event risk in a group of
      smokers undertaking pharmacologically unaided smoking cessation attempts with the event rate
      in a group of smokers attempting smoking cessation assisted by pharmacological interventions
      (any of nicotine replacement therapy, bupropion or varenicline) in a representative UK
      primary care population.

      There are three main types of pharmacological interventions currently available for smoking
      cessation, each of which has demonstrated efficacy when used in conjunction with behavioural
      support: nicotine replacement therapy, bupropion, and varenicline. Other medications,
      especially nortryptiline and clonidine, are considered to be effective adjunct therapy in
      smoking cessation, but they remain second-line options at this time.

      Nicotine replacement therapy has been available since the 1980s and bupropion since 2000.
      Either approach to cessation doubles the chance of achieving abstinence when compared with
      unsupported quit attempts. After being granted its European licence in 2006, varenicline
      joined the pharmacological smoking cessation armamentarium. It is the first drug developed
      specifically for the treatment of tobacco dependence that contains no nicotine, and it
      triples smokers' chances of quitting compared with unsupported quit attempts.

      As the fore-runner, nicotine replacement therapy is the longest-standing of the existing
      pharmacological smoking cessation interventions currently available. It aims to alleviate
      nicotine withdrawal symptoms by substituting the nicotine attained through tobacco smoking
      via alternative means (e.g. nasal sprays, inhalers, gum and tablets, transdermal patches).
      The various nicotine replacement therapy products available have differing durations of
      action and allow patients to tailor their nicotine intake according to their particular
      needs.For example, patches can be used to substitute for background nicotine and gums or
      tablets can be used to help satisfy urges.
observational model: Cohort
time perspective: Retrospective
measure: Time to first coronary heart disease diagnosis
time frame: 4 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior coronary heart disease.
measure: Time to first cerebrovascular disease diagnosis.
time frame: 4 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior cerebrovascular disease.
measure: Time to first coronary heart disease diagnosis
time frame: 52 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior coronary heart disease.
measure: Time to first cerebrovascular disease diagnosis
time frame: 52 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt. Excluding patients with prior cerebrovascular disease.
measure: Odds of recording one or more consultations for coronary heart disease or cerebrovascular disease
time frame: 52 weeks
description: Analysed using conditional logistic regression model. Recorded General Practice consultations or hospital attendances for coronary heart disease or cerebrovascular disease, including General Practice consultations, Accident & Emergency attendance, out-patient department attendance or in-patient admissions.
measure: Survival time for coronary heart disease-related death.
time frame: 52 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.
measure: Survival time for cerebrovascular disease-related death.
time frame: 52 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.
measure: Survival time for all-cause mortality.
time frame: 52 weeks
description: Analysed using Cox's proportional hazards model. Time from index smoking cessation attempt.
measure: Survival time for coronary heart disease-related death
time frame: Any time after index smoking cessation attempt
description: Analysed using Cox's proportional hazards model.
measure: Survival time for cerebrovascular disease-related death
time frame: Any time after index smoking cessation attempt
description: Analysed using Cox's proportional hazards model.
measure: Survival time for all-cause mortality
time frame: Any time after index smoking cessation attempt
description: Analysed using Cox's proportional hazards model.
arm group label: Nicotine replacement therapy cohort
description: Cohort defined as patients in whom nicotine replacement therapy (in any preparation) was initiated at the index smoking cessation attempt as the first recorded smoking cessation intervention.
arm group label: Other smoking cessation therapy
description: Cohort defined as patients in whom other (non-nicotine replacement therapy) smoking cessation pharmacotherapy's were initiated at the index smoking cessation attempt (e.g. bupropion, varenicline) as the first recorded smoking cessation intervention
arm group label: Smoking cessation advice cohort
description: Cohort (control patients) defined as patients whose first recorded smoking cessation intervention involved smoking cessation advice leading to a quit attempt unassisted by pharmacological smoking cessation aids, at the index smoking cessation attempt.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: David Price, Prof, MD
role: Principal Investigator
affiliation: University of Aberdeen
facility: 
country: United Kingdom
url: http://www.euro.who.int/__data/assets/pdf_file/0005/68117/E89842.pdf
description: World Health Organization (WHO). 2007. The European tobacco control report 2007 [online]
url: http://www.deathsfromsmoking.net
description: eto R, Lopez AD, Boreham J, et al. 2006. Mortality from smoking in developed countries 1950 - 2000 (2nd ed.) [online]
citation: Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence. Clinical practice guideline. Rockville (MD): US Department of Health and Human Services, Public Health Service, 2000
citation: West R, McNeill A, Raw M. Smoking cessation guidelines for health professionals: an update. Health Education Authority. Thorax. 2000 Dec;55(12):987-99. doi: 10.1136/thorax.55.12.987.
PMID: 11083883
citation: Le Foll B, George TP. Treatment of tobacco dependence: integrating recent progress into practice. CMAJ. 2007 Nov 20;177(11):1373-80. doi: 10.1503/cmaj.070627. Erratum In: CMAJ. 2008 Mar 11;178(6):732.
PMID: 18025429
citation: Stead LF, Perera R, Bullen C, Mant D, Lancaster T. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD000146. doi: 10.1002/14651858.CD000146.pub3.
PMID: 18253970
citation: Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006103. doi: 10.1002/14651858.CD006103.pub2.
PMID: 17253581
citation: British Medical Association and the Royal Pharmaceutical Society of Great Britain. British National Formulary. Version 56. London; BNF Group; 2008.
responsible party type: Sponsor
mesh term: Cardiovascular Diseases