<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/NCT01688908</url>
  </required_header>
  <id_info>
    <org_study_id>201202014</org_study_id>
    <nct_id>NCT01688908</nct_id>
  </id_info>
  <brief_title>Efficacy of Endoscopy Screening on Esophageal Cancer in China (ESECC)</brief_title>
  <acronym>ESECC</acronym>
  <official_title>Effcacy of Endoscopic Screening for Esophageal Cancer in China (ESECC): a Population-based Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the efficacy of endoscopic screening on esophageal cancer (EC) and determine the&#xD;
      most cost-effective strategy of endoscopic screening in high risk population in China, 668&#xD;
      villages of Hua county, a high risk area of esophageal cancer, were randomized into screening&#xD;
      arm and control arm in a ratio of 1:1 and the total sample size is over 32,000 (~16,000 per&#xD;
      group). Participants in the screening arm will accept standard chromoendoscopy examination to&#xD;
      detect early esophageal cancer and no screening were designed in the control arm. The&#xD;
      incidence of advanced EC, EC-specific mortality and all-cause mortality will be compared&#xD;
      within the two groups to test the hypothesis that endoscopic screening would alter the&#xD;
      natural history of lesions in esophagus and the incidence of advanced stage EC, EC-specific&#xD;
      mortality and all-cause mortality in the screening arm will be lower than the control group.&#xD;
      Cost-effectiveness analysis will also be conducted to find the most cost-effective strategy&#xD;
      of endoscopic screening in rural China.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND Esophageal cancer (EC) is one of the most common cancers in the world, and is a&#xD;
      leading cause of cancer death, with more than 450,000 new cases and 400,000 deaths in&#xD;
      2012.Nearly half of the new cases of EC worldwide are found in China, and esophageal squamous&#xD;
      cell carcinoma (ESCC) is the predominant histologic type. A series of etiologic factors for&#xD;
      ESCC have been proposed in previous studies conducted in high prevalence regions of China,&#xD;
      including age, family history of ESCC, poor nutritional status, smoking and drinking,&#xD;
      chemical carcinogen exposure, and human papillomavirus (HPV) infection. But the main&#xD;
      etiologic factors have not been definitively identified.&#xD;
&#xD;
      Because there are typically no symptoms in the early stages of ESCC, the vast majority of&#xD;
      cases are clinically diagnosed at an advanced stage. The overall five-year survival is about&#xD;
      20% in China, and is even lower in less developed countries. However, if the disease is found&#xD;
      at an early stage, the five-year survival may be 80% or greater. This profound improvement in&#xD;
      survival indicates there is clearly a need for effective early detection strategies to enable&#xD;
      earlier diagnosis and curative treatment. Esophageal squamous dysplasia (ESD) is considered&#xD;
      to be the premalignant precursor lesion for ESCC, and harbors a high risk for progression&#xD;
      into invasive cancer. ESD as well as early-stage malignant lesions (carcinoma in situ, CIS)&#xD;
      are therefore screening targets for ESCC. Various screening methods have been tested, and&#xD;
      endoscopy with iodine staining is the gold standard technique for the diagnosis of ESCC and&#xD;
      its precursor lesions. Endoscopic screening has therefore been widely accepted as an optimal&#xD;
      strategy in the secondary prevention of ESCC. However, taking the high cost and invasive&#xD;
      nature of endoscopy into consideration, the efficacy and cost-effectiveness of such&#xD;
      screening, must be evaluated prior to introduction of a population-wide screening program.&#xD;
      Evidence regarding the efficacy of endoscopic screening for ESCC has been based predominantly&#xD;
      on observational studies in high risk regions. There has been only one non-randomized&#xD;
      controlled trial which reported that endoscopy plays a positive role in reducing mortality.&#xD;
      No randomized controlled trials (RCTs) evaluating endoscopic screening have been reported to&#xD;
      date. Observational studies and trials which are not randomized are limited in determining&#xD;
      the true benefits of screening on reducing mortality due to potential lead-time bias,&#xD;
      length-time bias and confounding bias. Hence, one-step large-scale population-based RCT are&#xD;
      needed to determine the efficacy of endoscopic screening for ESCC.&#xD;
&#xD;
      In January 2012, we initiated the ESECC (Endoscopic Screening for Esophageal Cancer in China)&#xD;
      trial in rural Hua County of Henan Province, which is a high-risk region in northern central&#xD;
      China. This is the first population-based RCT aiming to evaluate the efficacy and&#xD;
      cost-effectiveness of endoscopic screening for ESCC worldwide.&#xD;
&#xD;
      STUDY DESIGN Setting and participants This ESECC trial was undertaken in rural Hua County,&#xD;
      which is an agricultural region in the northern part of Henan Province, Peoples Republic of&#xD;
      China with a rural population of 1.1 million. The mortality for ESCC in this area is among&#xD;
      the highest in the world.&#xD;
&#xD;
      Participants were eligible for the study if they meet the following criteria: 1) permanent&#xD;
      residency in a target village; 2) age 45-69 (&gt;5 years of life expectancy), and no history of&#xD;
      endoscopic examination within 5 years prior to the initial interview; 3) no history of cancer&#xD;
      or mental disorder; 4) negative for hepatitis B virus (HBV), hepatitis C virus (HCV) and&#xD;
      human immunodeficiency virus (HIV); 5) voluntary participation and agreement to complete all&#xD;
      phases of the examination.&#xD;
&#xD;
      Randomization This ESECC trial was designed as a cluster RCT. There are a total of 968&#xD;
      villages in rural Hua County, and 668 target villages were randomly selected from the 846&#xD;
      villages with population sizes ranging from 500 to 3,000 in Hua County. These 668 target&#xD;
      villages were randomly allocated into the screening arm of the study or the control arm at a&#xD;
      ratio of 1:1 (334 villages in each arm), using a blocked randomization procedure based on the&#xD;
      total population size of each village for balancing the sample sizes between the two study&#xD;
      arms.&#xD;
&#xD;
      Sample size According to the New Rural Cooperative Medical Scheme (NCMS) registration system&#xD;
      of Hua County, the combined incidence rate of advanced esophageal cancer and cancer of the&#xD;
      gastric cardia in the targeted population (age 45-69) was estimated to be 184.07/100,000 in&#xD;
      2011. Calculation of required sample size was based on the following assumptions: the average&#xD;
      period of progression from severe dysplasia to EC is 5 years, and the accrual time is 5&#xD;
      years; the study period was set at 10 years, and 5% of the participants would be lost to&#xD;
      follow-up per year; 5% of the participants in the control arm would seek endoscopic&#xD;
      examination independently during the study period. Finally, with a total of 32,337&#xD;
      participants enrolled (1:1 between arms, ~20% of all eligible residents in target villages),&#xD;
      statistical power of 86% at a one-sided 0.025 significance level can be achieved, even if&#xD;
      only 30% of advanced EC cases were protected by screening. The number of participants&#xD;
      enrolled in each target village was determined by the weight of the population size of the&#xD;
      very village in the total population of the whole arm.&#xD;
&#xD;
      Intervention An informed consent was obtained from each study participant. Basic information&#xD;
      including name, gender, date of birth, address and phone number was then collected and&#xD;
      managed using a custom-designed database system. All participants received a physical&#xD;
      examination which included measurement of height, weight and blood pressure. Blood samples&#xD;
      were collected to screen for HBV, HCV and HIV, and participants with any of these infections&#xD;
      were excluded. A computer aided one-on-one questionnaire investigation was conducted for all&#xD;
      participants by trained interviewers to collect data on potential risk factors for esophageal&#xD;
      cancer. EQ-5D-3L, a standardized generic instrument, was used in this ESECC trial to assess&#xD;
      health related quality of life (HRQOL).Standardized explanations regarding the items in the&#xD;
      questionnaire were provided if the participant was unable to understand the questions or&#xD;
      respond appropriately.&#xD;
&#xD;
      In the screening arm, standard upper gastrointestinal endoscopy (UGE) with iodine staining&#xD;
      was performed by physicians experienced in endoscopic examination. The entire esophagus and&#xD;
      stomach were visually examined and biopsies were taken from all focal lesions. Standard sites&#xD;
      in the esophagus (28 and 33 centimeters distal to the incisors in the 6 o'clock position)&#xD;
      were biopsied if no visually identifiable abnormalities were found elsewhere. Biopsy&#xD;
      specimens were fixed in 10% formaldehyde, embedded in paraffin, sectioned at 5μm, and stained&#xD;
      with hematoxylin and eosin. The biopsy slides were reviewed by pathologists at Anyang Cancer&#xD;
      Hospital without knowledge of the endoscopic findings. Diagnoses of ESD (mild, moderate and&#xD;
      severe), CIS and squamous cell carcinoma were independently confirmed by two pathologists and&#xD;
      discrepancies in their histologic diagnoses were adjudicated by consultation. To reflect the&#xD;
      situation in real population-level screening as much as possible, participants who were&#xD;
      diagnosed with severe squamous dysplasia, CIS or squamous cell carcinoma in the esophagus or&#xD;
      malignant lesions in other sites were only informed of the diagnosis and provided with&#xD;
      appropriate medical advice, rather than arranging directly for their further clinical&#xD;
      treatment.&#xD;
&#xD;
      In the control arm, no endoscopic screening was performed and an abdominal ultrasound scan&#xD;
      which had no association with the diagnosis of esophageal cancer was used.&#xD;
&#xD;
      Follow-up and outcomes The primary endpoint of the trial was EC-specific mortality, and the&#xD;
      secondary endpoints included mortality from all causes, incidence of advanced EC and cost per&#xD;
      quality-adjusted-life-year (QALY) gained. Two sources of follow-up data were used to identify&#xD;
      outcome events in this study, namely door-to-door interviews, and electronic registry data. A&#xD;
      record of vital events, including the experience of UGE, onset of cancer and death, will&#xD;
      continue to be collected through annual door-to-door interviews with all cohort members. Data&#xD;
      regarding cancer occurrence and death were also collected from the New Rural Cooperative&#xD;
      Medical Scheme (NCMS) of Hua County, which is a government-run health insurance program in&#xD;
      rural China with a nearly 100% participation rate which has been proved to be an ideal data&#xD;
      source regarding cancer occurrence, diagnosis and treatment, and from the Death Registry of&#xD;
      National Centers for Disease Control and Prevention (DR-CCDC) respectively.&#xD;
&#xD;
      Ethics statement This trial was approved by the Institutional Review Board of the Peking&#xD;
      University School of Oncology, China. Informed consent was obtained from each participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 1, 2012</start_date>
  <completion_date type="Anticipated">December 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>
    <primary_purpose>Screening</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Esophageal cancer specific mortality</measure>
    <time_frame>5-10 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cost for saving 1 quality-adjusted life year (QALY)</measure>
    <time_frame>5-10 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of advanced esophageal cancer</measure>
    <time_frame>5-10 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of life quality due to early diagnosis and treatment</measure>
    <time_frame>5-10 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33948</enrollment>
  <condition>Esophageal Squamous Cell Carcinoma</condition>
  <condition>Dysplasia</condition>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants in this arm will not accept the endoscopic screening and only baseline and follow-up interview will be conducted in this arm.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Screening Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this arm will accept a baseline endoscopic screening, questionnaire investigation and follow-up interview. Subsequent re-examination and further medical services would be arranged among individuals who already have high-grade lesions found at baseline screening.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Endoscopic Screening</intervention_name>
    <description>Upper G.I. endoscopic examination with Lugols Iodine in esophagus&#xD;
Biopsy at the visually abnormal sites&#xD;
Pathologic examination of all biopsy tissue specimens&#xD;
Subsequent re-examination and further medical services among individuals who already have high-grade lesions found at screening.&#xD;
Advises of endoscopic or surgical treatment will be given to participants who are diagnosed of high grade upper G.I. lesions.</description>
    <arm_group_label>Screening Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Participants were eligible for the study if they meet the following criteria: 1) permanent&#xD;
        residency in a target village; 2) age 45-69 (&gt;5 years of life expectancy), and no history&#xD;
        of endoscopic examination within 5 years prior to the initial interview; 3) no history of&#xD;
        cancer or mental disorder; 4) negative for hepatitis B virus (HBV), hepatitis C virus (HCV)&#xD;
        and human immunodeficiency virus (HIV); 5) voluntary participation and agreement to&#xD;
        complete all phases of the examination.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yang Ke, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laboratory of genetics, Peking University cancer Hospital and institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laboratory of genetics, Peking University cancer Hospital and institute</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/29306867</url>
    <description>Report of the design and preliminary results of the ESECC trial</description>
  </link>
  <results_reference>
    <citation>He Z, Liu Z, Liu M, Guo C, Xu R, Li F, Liu A, Yang H, Shen L, Wu Q, Duan L, Li X, Zhang C, Pan Y, Cai H, Ke Y. Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomised controlled trial. Gut. 2019 Feb;68(2):198-206. doi: 10.1136/gutjnl-2017-315520. Epub 2018 Jan 6.</citation>
    <PMID>29306867</PMID>
  </results_reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>January 18, 2018</last_update_submitted>
  <last_update_submitted_qc>January 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking University</investigator_affiliation>
    <investigator_full_name>Yang Ke</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Esophageal Squamous Cell Carcinoma</keyword>
  <keyword>Endoscopic Screening</keyword>
  <keyword>Efficacy</keyword>
  <keyword>Cost-utility</keyword>
  <keyword>High risk region</keyword>
  <keyword>China</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</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/NCT01688908
org study id: 201202014
nct id: NCT01688908
lead sponsor: 
has dmc: Yes
To evaluate the efficacy of endoscopic screening on esophageal cancer (EC) and determine the
      most cost-effective strategy of endoscopic screening in high risk population in China, 668
      villages of Hua county, a high risk area of esophageal cancer, were randomized into screening
      arm and control arm in a ratio of 1:1 and the total sample size is over 32,000 (~16,000 per
      group). Participants in the screening arm will accept standard chromoendoscopy examination to
      detect early esophageal cancer and no screening were designed in the control arm. The
      incidence of advanced EC, EC-specific mortality and all-cause mortality will be compared
      within the two groups to test the hypothesis that endoscopic screening would alter the
      natural history of lesions in esophagus and the incidence of advanced stage EC, EC-specific
      mortality and all-cause mortality in the screening arm will be lower than the control group.
      Cost-effectiveness analysis will also be conducted to find the most cost-effective strategy
      of endoscopic screening in rural China.
BACKGROUND Esophageal cancer (EC) is one of the most common cancers in the world, and is a
      leading cause of cancer death, with more than 450,000 new cases and 400,000 deaths in
      2012.Nearly half of the new cases of EC worldwide are found in China, and esophageal squamous
      cell carcinoma (ESCC) is the predominant histologic type. A series of etiologic factors for
      ESCC have been proposed in previous studies conducted in high prevalence regions of China,
      including age, family history of ESCC, poor nutritional status, smoking and drinking,
      chemical carcinogen exposure, and human papillomavirus (HPV) infection. But the main
      etiologic factors have not been definitively identified.

      Because there are typically no symptoms in the early stages of ESCC, the vast majority of
      cases are clinically diagnosed at an advanced stage. The overall five-year survival is about
      20% in China, and is even lower in less developed countries. However, if the disease is found
      at an early stage, the five-year survival may be 80% or greater. This profound improvement in
      survival indicates there is clearly a need for effective early detection strategies to enable
      earlier diagnosis and curative treatment. Esophageal squamous dysplasia (ESD) is considered
      to be the premalignant precursor lesion for ESCC, and harbors a high risk for progression
      into invasive cancer. ESD as well as early-stage malignant lesions (carcinoma in situ, CIS)
      are therefore screening targets for ESCC. Various screening methods have been tested, and
      endoscopy with iodine staining is the gold standard technique for the diagnosis of ESCC and
      its precursor lesions. Endoscopic screening has therefore been widely accepted as an optimal
      strategy in the secondary prevention of ESCC. However, taking the high cost and invasive
      nature of endoscopy into consideration, the efficacy and cost-effectiveness of such
      screening, must be evaluated prior to introduction of a population-wide screening program.
      Evidence regarding the efficacy of endoscopic screening for ESCC has been based predominantly
      on observational studies in high risk regions. There has been only one non-randomized
      controlled trial which reported that endoscopy plays a positive role in reducing mortality.
      No randomized controlled trials (RCTs) evaluating endoscopic screening have been reported to
      date. Observational studies and trials which are not randomized are limited in determining
      the true benefits of screening on reducing mortality due to potential lead-time bias,
      length-time bias and confounding bias. Hence, one-step large-scale population-based RCT are
      needed to determine the efficacy of endoscopic screening for ESCC.

      In January 2012, we initiated the ESECC (Endoscopic Screening for Esophageal Cancer in China)
      trial in rural Hua County of Henan Province, which is a high-risk region in northern central
      China. This is the first population-based RCT aiming to evaluate the efficacy and
      cost-effectiveness of endoscopic screening for ESCC worldwide.

      STUDY DESIGN Setting and participants This ESECC trial was undertaken in rural Hua County,
      which is an agricultural region in the northern part of Henan Province, Peoples Republic of
      China with a rural population of 1.1 million. The mortality for ESCC in this area is among
      the highest in the world.

      Participants were eligible for the study if they meet the following criteria: 1) permanent
      residency in a target village; 2) age 45-69 (>5 years of life expectancy), and no history of
      endoscopic examination within 5 years prior to the initial interview; 3) no history of cancer
      or mental disorder; 4) negative for hepatitis B virus (HBV), hepatitis C virus (HCV) and
      human immunodeficiency virus (HIV); 5) voluntary participation and agreement to complete all
      phases of the examination.

      Randomization This ESECC trial was designed as a cluster RCT. There are a total of 968
      villages in rural Hua County, and 668 target villages were randomly selected from the 846
      villages with population sizes ranging from 500 to 3,000 in Hua County. These 668 target
      villages were randomly allocated into the screening arm of the study or the control arm at a
      ratio of 1:1 (334 villages in each arm), using a blocked randomization procedure based on the
      total population size of each village for balancing the sample sizes between the two study
      arms.

      Sample size According to the New Rural Cooperative Medical Scheme (NCMS) registration system
      of Hua County, the combined incidence rate of advanced esophageal cancer and cancer of the
      gastric cardia in the targeted population (age 45-69) was estimated to be 184.07/100,000 in
      2011. Calculation of required sample size was based on the following assumptions: the average
      period of progression from severe dysplasia to EC is 5 years, and the accrual time is 5
      years; the study period was set at 10 years, and 5% of the participants would be lost to
      follow-up per year; 5% of the participants in the control arm would seek endoscopic
      examination independently during the study period. Finally, with a total of 32,337
      participants enrolled (1:1 between arms, ~20% of all eligible residents in target villages),
      statistical power of 86% at a one-sided 0.025 significance level can be achieved, even if
      only 30% of advanced EC cases were protected by screening. The number of participants
      enrolled in each target village was determined by the weight of the population size of the
      very village in the total population of the whole arm.

      Intervention An informed consent was obtained from each study participant. Basic information
      including name, gender, date of birth, address and phone number was then collected and
      managed using a custom-designed database system. All participants received a physical
      examination which included measurement of height, weight and blood pressure. Blood samples
      were collected to screen for HBV, HCV and HIV, and participants with any of these infections
      were excluded. A computer aided one-on-one questionnaire investigation was conducted for all
      participants by trained interviewers to collect data on potential risk factors for esophageal
      cancer. EQ-5D-3L, a standardized generic instrument, was used in this ESECC trial to assess
      health related quality of life (HRQOL).Standardized explanations regarding the items in the
      questionnaire were provided if the participant was unable to understand the questions or
      respond appropriately.

      In the screening arm, standard upper gastrointestinal endoscopy (UGE) with iodine staining
      was performed by physicians experienced in endoscopic examination. The entire esophagus and
      stomach were visually examined and biopsies were taken from all focal lesions. Standard sites
      in the esophagus (28 and 33 centimeters distal to the incisors in the 6 o'clock position)
      were biopsied if no visually identifiable abnormalities were found elsewhere. Biopsy
      specimens were fixed in 10% formaldehyde, embedded in paraffin, sectioned at 5μm, and stained
      with hematoxylin and eosin. The biopsy slides were reviewed by pathologists at Anyang Cancer
      Hospital without knowledge of the endoscopic findings. Diagnoses of ESD (mild, moderate and
      severe), CIS and squamous cell carcinoma were independently confirmed by two pathologists and
      discrepancies in their histologic diagnoses were adjudicated by consultation. To reflect the
      situation in real population-level screening as much as possible, participants who were
      diagnosed with severe squamous dysplasia, CIS or squamous cell carcinoma in the esophagus or
      malignant lesions in other sites were only informed of the diagnosis and provided with
      appropriate medical advice, rather than arranging directly for their further clinical
      treatment.

      In the control arm, no endoscopic screening was performed and an abdominal ultrasound scan
      which had no association with the diagnosis of esophageal cancer was used.

      Follow-up and outcomes The primary endpoint of the trial was EC-specific mortality, and the
      secondary endpoints included mortality from all causes, incidence of advanced EC and cost per
      quality-adjusted-life-year (QALY) gained. Two sources of follow-up data were used to identify
      outcome events in this study, namely door-to-door interviews, and electronic registry data. A
      record of vital events, including the experience of UGE, onset of cancer and death, will
      continue to be collected through annual door-to-door interviews with all cohort members. Data
      regarding cancer occurrence and death were also collected from the New Rural Cooperative
      Medical Scheme (NCMS) of Hua County, which is a government-run health insurance program in
      rural China with a nearly 100% participation rate which has been proved to be an ideal data
      source regarding cancer occurrence, diagnosis and treatment, and from the Death Registry of
      National Centers for Disease Control and Prevention (DR-CCDC) respectively.

      Ethics statement This trial was approved by the Institutional Review Board of the Peking
      University School of Oncology, China. Informed consent was obtained from each participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Screening
masking: Single (Outcomes Assessor)
measure: Esophageal cancer specific mortality
time frame: 5-10 years
measure: Cost for saving 1 quality-adjusted life year (QALY)
time frame: 5-10 years
measure: Cumulative incidence of advanced esophageal cancer
time frame: 5-10 years
measure: Change of life quality due to early diagnosis and treatment
time frame: 5-10 years
arm group label: Control Arm
arm group type: No Intervention
description: Participants in this arm will not accept the endoscopic screening and only baseline and follow-up interview will be conducted in this arm.
arm group label: Screening Arm
arm group type: Experimental
description: Participants in this arm will accept a baseline endoscopic screening, questionnaire investigation and follow-up interview. Subsequent re-examination and further medical services would be arranged among individuals who already have high-grade lesions found at baseline screening.
intervention type: Procedure
intervention name: Endoscopic Screening
description: Upper G.I. endoscopic examination with Lugols Iodine in esophagus
Biopsy at the visually abnormal sites
Pathologic examination of all biopsy tissue specimens
Subsequent re-examination and further medical services among individuals who already have high-grade lesions found at screening.
Advises of endoscopic or surgical treatment will be given to participants who are diagnosed of high grade upper G.I. lesions.
arm group label: Screening Arm
criteria: 
gender: All
minimum age: 45 Years
maximum age: 69 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yang Ke, M.D.
role: Principal Investigator
affiliation: Laboratory of genetics, Peking University cancer Hospital and institute
facility: 
country: China
url: https://www.ncbi.nlm.nih.gov/pubmed/29306867
description: Report of the design and preliminary results of the ESECC trial
citation: He Z, Liu Z, Liu M, Guo C, Xu R, Li F, Liu A, Yang H, Shen L, Wu Q, Duan L, Li X, Zhang C, Pan Y, Cai H, Ke Y. Efficacy of endoscopic screening for esophageal cancer in China (ESECC): design and preliminary results of a population-based randomised controlled trial. Gut. 2019 Feb;68(2):198-206. doi: 10.1136/gutjnl-2017-315520. Epub 2018 Jan 6.
PMID: 29306867
responsible party type: Principal Investigator
investigator affiliation: Peking University
investigator full name: Yang Ke
investigator title: Professor
mesh term: Carcinoma, Squamous Cell
mesh term: Esophageal Neoplasms
mesh term: Esophageal Squamous Cell Carcinoma