<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/NCT03836560</url>
  </required_header>
  <id_info>
    <org_study_id>HA_SCCP_NRT</org_study_id>
    <nct_id>NCT03836560</nct_id>
  </id_info>
  <brief_title>Comparing the Effectiveness of Combined NRT With Single NRT in Primary Care Clinics in Hong Kong</brief_title>
  <official_title>Comparing the Effectiveness of Nicotine Patch With Gum Versus Nicotine Patch Alone in Smoking Cessation in Hong Kong Primary Care Clinics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Authority, Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Chinese University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Authority, Hong Kong</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The prevalence of cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however,&#xD;
      smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher&#xD;
      with combined NRT than single NRT, although local data on safety and benefits of combined NRT&#xD;
      are lacking.&#xD;
&#xD;
      This is a one-year, two-arm, parallel randomized trial in 20 HK public clinics. The aim is to&#xD;
      compare the effectiveness of combined NRT with single NRT among HK Chinese. 560 chronic&#xD;
      smokers, who smoked ≥10 cigarettes/day for ≥ 1 year, were randomized to either intervention&#xD;
      or usual care.&#xD;
&#xD;
      Intervention group received counseling and nicotine patch &amp; gum. Usual care group received&#xD;
      counselling and nicotine patch only. Primary outcome was smoking abstinence rate at 52 weeks.&#xD;
      Secondary outcomes included smoking abstinence rate at 4, 12, &amp; 26 weeks. Crude odds ratio&#xD;
      (combined NRT vs. single NRT) and p-value were reported from logistic regression without&#xD;
      adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from&#xD;
      Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age,&#xD;
      sex, baseline CO and clusters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background Globally, smoking causes six million deaths a year1. By 2030, if current trends&#xD;
      continue, the number of deaths will rise to eight million. According to Hong Kong Thematic&#xD;
      Household Survey Reports, although the prevalence of current smokers among aged 15 and over&#xD;
      has dropped from 15.3% in 2006 to 10.8% in 2017 in Hong Kong, smoking still kills 5700&#xD;
      persons per year and contributes to 14% of all deaths from non-communicable diseases. Thus,&#xD;
      enhancement in smoking cessation would be crucial in improving health all smokers.&#xD;
&#xD;
      Among all pharmacological treatment for smoking cessation, evidences showed that oral&#xD;
      treatment such as Varenicline is the most clinically effective smoking cessation medication9.&#xD;
      However, there have been concerns about its adverse effect on neuropsychiatric and&#xD;
      cardiovascular aspects. Besides, many smokers are reluctant to use it due to fear of its high&#xD;
      rate of side effects and being medicalized for smoking cessation. The use of nicotine&#xD;
      replacement therapy (NRT) has been largely studied, and, over the last decade, many studies&#xD;
      had been carried out to compare the effect of monotherapy with combined nicotine replacement&#xD;
      therapy. While the effect of monotherapy had been found to be small in heavy smokers due to&#xD;
      significant withdrawal symptoms, combined NRT is believed to provide a stable baseline&#xD;
      nicotine level by means of nicotine patch plus intermittent usage of short acting NRT e.g.&#xD;
      gums, lozenges or inhalers for withdrawal symptoms. Several studies have shown that combined&#xD;
      NRT is associated with lower withdrawal scores and higher 6-month quit rates (26.9 to 36.9%)&#xD;
      when compared with monotherapies (19-23%)18-21. Combined NRT has also been shown to be safe&#xD;
      as trials of combining various NRTs did not report that combination treatment produced&#xD;
      increased adverse events.&#xD;
&#xD;
      In Hong Kong, Hospital Authority is one of the major service providers for smoking cessation.&#xD;
      The target recipients of our smoking cessation service are primarily patients attending&#xD;
      public general out-patient clinics (GOPCs) for management of chronic illnesses such as&#xD;
      hypertension and diabetes mellitus, as well as patients with episodic complaints. Through&#xD;
      effective interventions provided in the smoking cessation service, it is aimed that their&#xD;
      medical conditions could be further improved. However, as majority of these smokers have&#xD;
      moderate or above nicotine dependence, how effective is combined NRT compared to single NRT&#xD;
      in this Chinese population is unknown.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      Combined NRT gives a higher abstinence rate than single NRT.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      This study aims to compare the effectiveness of combined NRT with single NRT in Hong Kong&#xD;
      primary care clinics.&#xD;
&#xD;
      Assessment Patients were seen at baseline for assessment, and then at 4 weeks, 12 weeks, 26&#xD;
      weeks and 52 weeks. Study medication was given at baseline and at week 4. In baseline&#xD;
      assessment, smoking history including daily cigarette consumption and past quitting method,&#xD;
      past medical health, drug history and allergy would be obtained. In follow up visits patients&#xD;
      were assessed on nicotine withdrawal symptoms, carbon monoxide level, side effects from&#xD;
      treatment and medication compliance. Counselling would be given in all follow up visits.&#xD;
&#xD;
      Pharmacological interventions Patients were randomized to either intervention or usual care&#xD;
      for smoking cessation. Nicotine replacement therapy (NRT) was given for 8 weeks in both arms.&#xD;
      Intervention consisted of counseling and combined NRT of nicotine patch and gum. Usual care&#xD;
      involved counseling and single NRT of nicotine patch. NRT patch regimen used in usual care&#xD;
      was the same as that in intervention group.&#xD;
&#xD;
      Data analysis Baseline characteristics were reported and compared by treatment groups,&#xD;
      two-sample t test was conducted for continuous variables and Chi-square test for categorical&#xD;
      variables. At each visit, crude odds ratio (OR) (combined NRT vs. single NRT) was reported,&#xD;
      simple logistic regression was utilized without adjustment first, and then adjusted for&#xD;
      potential confounders, age, sex, baseline CO level and cluster site of the subject&#xD;
      recruitment. The overall treatment effect (combined NRT vs. single NRT) over the study period&#xD;
      was estimated by Generalized Estimating Equation (GEE). In the GEE model, time (repeated&#xD;
      measures at 4, 12, 26, and 52 weeks) was included as a continuous covariate, adjusted odds&#xD;
      ratio (AOR) was reported and treatment-time interaction was tested. Potential confounders&#xD;
      were also adjusted for in the GEE model. As GEE only uses non-missing records, missing at&#xD;
      complete random was assumed to avoid bias. To support the random missing assumption,&#xD;
      supplementary analysis was conducted for missingness pattern Furthermore, imputation was&#xD;
      conducted under a conservative scenario of 'all missing records as &quot;failure&quot;, i.e., not&#xD;
      quit'. Statistical significance level was set at two-sided p&lt;0.05 for all tests. Analysis was&#xD;
      conducted by R version 3.2.235. Side effects from NRT were also recorded from both groups.&#xD;
      Chi-squared test was used to compare the difference.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2012</start_date>
  <completion_date type="Actual">February 28, 2018</completion_date>
  <primary_completion_date type="Actual">February 28, 2018</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>One year, 2 arm, parallel, randomised controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The outcome assessor did not know which arm was interventional/control during the data analysis process.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>7-day point-prevalence abstinence rate at 52 weeks after quit date</measure>
    <time_frame>at 52 weeks after the agreed quit date</time_frame>
    <description>During initial assessment, patient will set a quit date with the counsellor. At 52 weeks after the quit rate, counsellor will call the patient and confirm his quit status. The status was confirmed by self reporting abstinence rate and exhaled carbon monoxide level</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>side effects profiles</measure>
    <time_frame>up to 1 year</time_frame>
    <description>side effects from nicotine replacement therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>7-day point-prevalence of abstinence rate at 26 weeks after quit date</measure>
    <time_frame>at 26 weeks after the agreed quit date</time_frame>
    <description>During initial assessment, patient will set a quit date with the counsellor. At 26 weeks after the quit rate, counsellor will call the patient and confirm his quit status. The status was confirmed by self reporting abstinence rate and exhaled carbon monoxide level</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">560</enrollment>
  <condition>Smoking Cessation</condition>
  <arm_group>
    <arm_group_label>Usual group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Usual group with nicotine patch only:&#xD;
Usual care involved counseling and 8 weeks of single NRT of nicotine patch. For those smoking 20 or more cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 21mg patches, then 2 weeks of 14mg patches, followed by 2 weeks of 7mg patches. For those smoking 10 to 19 cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 14mg patches, followed by 4 weeks of 7mg patches.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nicotine patch and nicotine gum:&#xD;
Intervention consisted of counseling and 8 weeks of combined NRT of nicotine patch and gum. For those smoking 20 or more cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 21mg patches, then 2 weeks of 14mg patches, followed by 2 weeks of 7mg patches. For those smoking 10 to 19 cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 14mg patches, followed by 4 weeks of 7mg patches. 2mg nicotine gum was used once every 1 to 2 hours when required.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine patch</intervention_name>
    <description>nicotine patch given for 8 weeks</description>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_label>Usual group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nicotine gum</intervention_name>
    <description>nicotine gum given as requested</description>
    <arm_group_label>Intervention group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  current smokers who smoke 10 or more cigarettes a day for at least one year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  unstable angina&#xD;
&#xD;
          -  severe cardiac arrhythmia&#xD;
&#xD;
          -  recent acute myocardial infarction or cerebrovascular accident in preceding 3 months&#xD;
&#xD;
          -  below 18 years old&#xD;
&#xD;
          -  being pregnant or on breast-feeding&#xD;
&#xD;
          -  unable to use gum&#xD;
&#xD;
          -  with a previous history of failure to NRT&#xD;
&#xD;
          -  with a history of hypersensitivity to nicotine&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Chao, FHKAM</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Authority</affiliation>
  </overall_official>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>February 7, 2019</last_update_submitted>
  <last_update_submitted_qc>February 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Authority, Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr Maria Leung</investigator_full_name>
    <investigator_title>Consultant in Family Medicine</investigator_title>
  </responsible_party>
  <keyword>nicotine replacement therapy</keyword>
  <keyword>smoking cessation</keyword>
  <keyword>quit rates</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>We plan to provide a dropbox link</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Study protocol and statistical analysis plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2012</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03836560/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Results of the study</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/60/NCT03836560/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03836560
org study id: HA_SCCP_NRT
nct id: NCT03836560
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The prevalence of cigarette smoking has dropped to 10% in Hong Kong (HK) in 2017, however,
      smoking still kills 5700 persons per year. Studies suggest that abstinence rates are higher
      with combined NRT than single NRT, although local data on safety and benefits of combined NRT
      are lacking.

      This is a one-year, two-arm, parallel randomized trial in 20 HK public clinics. The aim is to
      compare the effectiveness of combined NRT with single NRT among HK Chinese. 560 chronic
      smokers, who smoked ≥10 cigarettes/day for ≥ 1 year, were randomized to either intervention
      or usual care.

      Intervention group received counseling and nicotine patch & gum. Usual care group received
      counselling and nicotine patch only. Primary outcome was smoking abstinence rate at 52 weeks.
      Secondary outcomes included smoking abstinence rate at 4, 12, & 26 weeks. Crude odds ratio
      (combined NRT vs. single NRT) and p-value were reported from logistic regression without
      adjustment; for trend analysis, adjusted odds ratio (AOR) and p-value were reported from
      Generalized Estimating Equation (GEE) (controlling for time). All AORs were adjusted for age,
      sex, baseline CO and clusters.
Background Globally, smoking causes six million deaths a year1. By 2030, if current trends
      continue, the number of deaths will rise to eight million. According to Hong Kong Thematic
      Household Survey Reports, although the prevalence of current smokers among aged 15 and over
      has dropped from 15.3% in 2006 to 10.8% in 2017 in Hong Kong, smoking still kills 5700
      persons per year and contributes to 14% of all deaths from non-communicable diseases. Thus,
      enhancement in smoking cessation would be crucial in improving health all smokers.

      Among all pharmacological treatment for smoking cessation, evidences showed that oral
      treatment such as Varenicline is the most clinically effective smoking cessation medication9.
      However, there have been concerns about its adverse effect on neuropsychiatric and
      cardiovascular aspects. Besides, many smokers are reluctant to use it due to fear of its high
      rate of side effects and being medicalized for smoking cessation. The use of nicotine
      replacement therapy (NRT) has been largely studied, and, over the last decade, many studies
      had been carried out to compare the effect of monotherapy with combined nicotine replacement
      therapy. While the effect of monotherapy had been found to be small in heavy smokers due to
      significant withdrawal symptoms, combined NRT is believed to provide a stable baseline
      nicotine level by means of nicotine patch plus intermittent usage of short acting NRT e.g.
      gums, lozenges or inhalers for withdrawal symptoms. Several studies have shown that combined
      NRT is associated with lower withdrawal scores and higher 6-month quit rates (26.9 to 36.9%)
      when compared with monotherapies (19-23%)18-21. Combined NRT has also been shown to be safe
      as trials of combining various NRTs did not report that combination treatment produced
      increased adverse events.

      In Hong Kong, Hospital Authority is one of the major service providers for smoking cessation.
      The target recipients of our smoking cessation service are primarily patients attending
      public general out-patient clinics (GOPCs) for management of chronic illnesses such as
      hypertension and diabetes mellitus, as well as patients with episodic complaints. Through
      effective interventions provided in the smoking cessation service, it is aimed that their
      medical conditions could be further improved. However, as majority of these smokers have
      moderate or above nicotine dependence, how effective is combined NRT compared to single NRT
      in this Chinese population is unknown.

      Hypothesis:

      Combined NRT gives a higher abstinence rate than single NRT.

      Objective:

      This study aims to compare the effectiveness of combined NRT with single NRT in Hong Kong
      primary care clinics.

      Assessment Patients were seen at baseline for assessment, and then at 4 weeks, 12 weeks, 26
      weeks and 52 weeks. Study medication was given at baseline and at week 4. In baseline
      assessment, smoking history including daily cigarette consumption and past quitting method,
      past medical health, drug history and allergy would be obtained. In follow up visits patients
      were assessed on nicotine withdrawal symptoms, carbon monoxide level, side effects from
      treatment and medication compliance. Counselling would be given in all follow up visits.

      Pharmacological interventions Patients were randomized to either intervention or usual care
      for smoking cessation. Nicotine replacement therapy (NRT) was given for 8 weeks in both arms.
      Intervention consisted of counseling and combined NRT of nicotine patch and gum. Usual care
      involved counseling and single NRT of nicotine patch. NRT patch regimen used in usual care
      was the same as that in intervention group.

      Data analysis Baseline characteristics were reported and compared by treatment groups,
      two-sample t test was conducted for continuous variables and Chi-square test for categorical
      variables. At each visit, crude odds ratio (OR) (combined NRT vs. single NRT) was reported,
      simple logistic regression was utilized without adjustment first, and then adjusted for
      potential confounders, age, sex, baseline CO level and cluster site of the subject
      recruitment. The overall treatment effect (combined NRT vs. single NRT) over the study period
      was estimated by Generalized Estimating Equation (GEE). In the GEE model, time (repeated
      measures at 4, 12, 26, and 52 weeks) was included as a continuous covariate, adjusted odds
      ratio (AOR) was reported and treatment-time interaction was tested. Potential confounders
      were also adjusted for in the GEE model. As GEE only uses non-missing records, missing at
      complete random was assumed to avoid bias. To support the random missing assumption,
      supplementary analysis was conducted for missingness pattern Furthermore, imputation was
      conducted under a conservative scenario of 'all missing records as "failure", i.e., not
      quit'. Statistical significance level was set at two-sided p<0.05 for all tests. Analysis was
      conducted by R version 3.2.235. Side effects from NRT were also recorded from both groups.
      Chi-squared test was used to compare the difference.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: One year, 2 arm, parallel, randomised controlled trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The outcome assessor did not know which arm was interventional/control during the data analysis process.
measure: 7-day point-prevalence abstinence rate at 52 weeks after quit date
time frame: at 52 weeks after the agreed quit date
description: During initial assessment, patient will set a quit date with the counsellor. At 52 weeks after the quit rate, counsellor will call the patient and confirm his quit status. The status was confirmed by self reporting abstinence rate and exhaled carbon monoxide level
measure: side effects profiles
time frame: up to 1 year
description: side effects from nicotine replacement therapy
measure: 7-day point-prevalence of abstinence rate at 26 weeks after quit date
time frame: at 26 weeks after the agreed quit date
description: During initial assessment, patient will set a quit date with the counsellor. At 26 weeks after the quit rate, counsellor will call the patient and confirm his quit status. The status was confirmed by self reporting abstinence rate and exhaled carbon monoxide level
arm group label: Usual group
arm group type: Active Comparator
description: Usual group with nicotine patch only:
Usual care involved counseling and 8 weeks of single NRT of nicotine patch. For those smoking 20 or more cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 21mg patches, then 2 weeks of 14mg patches, followed by 2 weeks of 7mg patches. For those smoking 10 to 19 cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 14mg patches, followed by 4 weeks of 7mg patches.
arm group label: Intervention group
arm group type: Active Comparator
description: Nicotine patch and nicotine gum:
Intervention consisted of counseling and 8 weeks of combined NRT of nicotine patch and gum. For those smoking 20 or more cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 21mg patches, then 2 weeks of 14mg patches, followed by 2 weeks of 7mg patches. For those smoking 10 to 19 cigarettes per day before quitting, the NRT patch regimen was 4 weeks of 14mg patches, followed by 4 weeks of 7mg patches. 2mg nicotine gum was used once every 1 to 2 hours when required.
intervention type: Drug
intervention name: Nicotine patch
description: nicotine patch given for 8 weeks
arm group label: Intervention group
arm group label: Usual group
intervention type: Drug
intervention name: Nicotine gum
description: nicotine gum given as requested
arm group label: Intervention group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: David Chao, FHKAM
role: Study Chair
affiliation: Hospital Authority
responsible party type: Principal Investigator
investigator affiliation: Hospital Authority, Hong Kong
investigator full name: Dr Maria Leung
investigator title: Consultant in Family Medicine
mesh term: Nicotine
sharing ipd: Undecided
ipd description: We plan to provide a dropbox link
provided document: 
provided document: 