<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/NCT03304028</url>
  </required_header>
  <id_info>
    <org_study_id>C16-119</org_study_id>
    <secondary_id>2017-A00723-50</secondary_id>
    <nct_id>NCT03304028</nct_id>
  </id_info>
  <brief_title>MUCOviscidose EXacerbation Outils Connectés Education Thérapeutique</brief_title>
  <acronym>MucoExocet</acronym>
  <official_title>Use of Home-based Connected Devices to Early Detect and Treat Pulmonary Exacerbations: Feasibility and Clinical Validity in CF Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondation pour la Recherche Médicale</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vertex Pharmaceuticals Incorporated</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fondation Ildys</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Institut National de la Santé Et de la Recherche Médicale, France</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>
      Early detection of pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) patients is&#xD;
      important to quickly trigger treatment and reduce respiratory damage. The investigators&#xD;
      hypothesize that using home-based connected devices (CDs) in educated patients applying&#xD;
      Cumulative sum charts (CUSUM) to monitor physiological parameters (PP) and patients'&#xD;
      perception reported (PRP), will allow early detection of PEx.&#xD;
&#xD;
      Objective: to study clinical validity of using CDs and evaluate adherence and satisfaction in&#xD;
      CF patients and teams&#xD;
&#xD;
      Design: 3 phase multicenter study in 36 CF patients aged &gt;=12 years. Phase 1, patients are&#xD;
      equipped during 3 months with CDs. PP and PRP to estimate CUSUM parameters are collected. In&#xD;
      phase 2, patient's personalized educational plan to manage alerts is built. In phase 3, PP&#xD;
      and PRP are collected during 12 months. Clinical validity, change in patients clinical data,&#xD;
      quality of Life/Anxiety-Depression/Satisfaction, patients and teams' acceptance and adherence&#xD;
      are assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND&#xD;
&#xD;
      Pulmonary exacerbations (PEx) are the major cause of lung function decline in Cystic Fibrosis&#xD;
      (CF) patients leading to respiratory failure. Identifying warning signs of PEx is a priority&#xD;
      to trigger early treatment and reduce respiratory damage. Some authors tried to define scores&#xD;
      based on symptoms to standardize treatment. However, lack of consensus led the&#xD;
      Euro-Care-CF-Working-Group to recommend the use of medical antibiotic treatment decision (or&#xD;
      treatment modification) associated with PEx-like symptoms as best definition of PEx for&#xD;
      clinical trials.&#xD;
&#xD;
      A DELPHI study identified 10 signs frequently perceived by patients and 10 most often cited&#xD;
      indicators by caregivers. Two studies have shown that a combination of physiological&#xD;
      parameters (PP) and patient reported perceptions (PRP) such as weight loss, decreased&#xD;
      spirometry , increased cough or increased sputum production reported daily, help diagnose PEx&#xD;
      episodes and trigger early treatment. Clinical observations show that changes in PP and PRP&#xD;
      related to PEx differ according to age and degree of lung function impairment. Currently,&#xD;
      patients with CF do not routinely monitor their lung function at home, nor do they&#xD;
      objectively track PP or PRP. Consequently, CF PEx can be diagnosed late when symptoms&#xD;
      progress, in which they seek medical care. Thus, development of an effective approach that&#xD;
      helps to monitor daily indicators of PEx to early identification and treatment is important.&#xD;
&#xD;
        -  Home monitoring of PEx symptoms Several studies have been conducted with daily&#xD;
           monitoring of PEx symptoms. Most of these studies monitored one or two respiratory&#xD;
           parameters with data transmission to the medical staff who decide what course of action&#xD;
           to take. In addition, these studies used for each parameter the same alert limit for all&#xD;
           patients, as it is known that patients with CF have different thresholds of these&#xD;
           indicators,some may present more frequently than others.&#xD;
&#xD;
        -  CUSUM to monitor indicators of pulmonary exacerbation The use of statistical process&#xD;
           control (SPC) shows promise for monitoring indicators of CF PEx and rapidly detecting&#xD;
           unwanted changes in these indicators. SPC uses rigorous time-series analysis methods,&#xD;
           with results reported as a graph of changes in indicators over time[9]. Moreover, SPC&#xD;
           can help to determine whether these changes are real (related to a causative factor) or&#xD;
           merely a manifestation of natural variability. Among SPC, cumulative sum (CUSUM) chart&#xD;
           has been found effective for measuring and monitoring healthcare outcome. It detects&#xD;
           changes rapidly, and can identify small shifts. Connected devices software programming&#xD;
           integrating CUSUM alert limits can help to determine whether the changes in PP and PRT&#xD;
           are due to real PEx episode.&#xD;
&#xD;
      STUDY HYPOTHESIS The investigators hypothesize that using home-based CDs applying CUSUM with&#xD;
      patient's personalized alert limits to monitor physiological data and PRP combined with&#xD;
      patient education allows early detection of PEx. Studying alerts can help clinicians to&#xD;
      develop a patient's personalized educational plan allowing patients better management of PEx&#xD;
      including ability to make informed choices. This study aims to assess clinical validity of&#xD;
      using different CDs, acceptance and adherence of patients of data collection of physiological&#xD;
      data and PRPs, and acceptance by the clinical teams of this process of care. It will lead a&#xD;
      larger trial aiming to evaluate efficacy of this process of care on patient's clinical&#xD;
      outcomes.&#xD;
&#xD;
      DESIGN&#xD;
&#xD;
      Design: A 3 phase multi-center prospective longitudinal pilot study will be conducted.&#xD;
&#xD;
      - Phase 1- Baseline data collection Clinic staff will email all patients or parents&#xD;
      (pediatric settings) to introduce the study. A qualitative interview with 10 patients who&#xD;
      declined to participate in the study will be conducted to identify the reason of refusal.&#xD;
&#xD;
      M0: Inclusion visit: the inclusion will be proposed at a follow-up visit by the child's or&#xD;
      adult's referring doctor. A written informed consent form will be obtained from all adults or&#xD;
      both parents of children.&#xD;
&#xD;
      Quality of Life and Anxiety-Depression will be collected using the HADS and CFQ-R scale Each&#xD;
      included patient will be equipped with CDs-spirometer, oxymeter, scale and watch During 3&#xD;
      months: Baseline data of 14 warning indicators of Pex will be collected during 3 non&#xD;
      consecutive days a week using the CDs.&#xD;
&#xD;
      Number and time of acute PEx, FEV1, weight, respiratory symptoms and antibiotic treatments&#xD;
      prescribed will be collected at the end of the period from the medical patient chart in the&#xD;
      CF centre.&#xD;
&#xD;
        -  Phase 2- statistical analysis and patient education Statistical analysis of the data&#xD;
           collected in phase 1 will take place to calculate the CUSUM parameters. Alert parameters&#xD;
           for each patient are then fixed. An educational visit will be scheduled with patients&#xD;
&#xD;
        -  Phase 3- CDs use and personalized care PP and PRP will be continuously collected during&#xD;
           12 months using CDs. If alerts occur, patients will be informed by email or SMS, with&#xD;
           data transmission to the medical team who will not interfere. Patients should apply the&#xD;
           shared action plan they learned. Quality of Life and Anxiety-Depression will be&#xD;
           collected using the HADS and CFQ-R scale. Number and time of acute PEx, FEV1, weight,&#xD;
           respiratory symptoms and antibiotic treatments prescribed during the period will be&#xD;
           collected at the end of the period from the medical patient chart in the CF centre.&#xD;
&#xD;
      At the end of Phase 3: Semi-structured interviews will be completed with the 30&#xD;
      patients/parents and 5 medical teams to explore confidence on the CDs, impact on the&#xD;
      doctor-patient relationship, change in the workload of medical team…etc.&#xD;
&#xD;
      EXPECTED RESULTS&#xD;
&#xD;
      The investigators expect a better quality of life for patients, and that their&#xD;
      anxiety-depression has not increased or rather decreased. For the clinical teams, the&#xD;
      investigators aim to demonstrate that the use of CDs at home by educated patients is&#xD;
      acceptable in their daily workload, and satisfying regarding the application of the shared&#xD;
      action plan by the patient. Unlike other studies, patients are empowered to initiate actions&#xD;
      when alerted by variations of the parameters. If they don't follow the action plan decided&#xD;
      with the clinical teams, the treatment of PEx might not be earlier than if they didn't use&#xD;
      CDs. In that case, a discussion with the clinicians may lead to the alternative process in&#xD;
      which the alerts are used by the clinical teams to drive the actions for the patient.&#xD;
      Interestingly, this alternative is possible because the alerts are simultaneously transmitted&#xD;
      to the patient and to the team. The leader in the process may even change at some critical&#xD;
      periods when the patient is in bad condition or depressed.&#xD;
&#xD;
      Qualitative analysis will provide knowledge on benefits and pitfalls to improve confidence in&#xD;
      the use of CDS at home from the patients and the clinical teams, improve the patient-team&#xD;
      partnership and, decrease stress and anxiety about pulmonary exacerbation treatment. This&#xD;
      study will lead to further plan a larger trial aiming to evaluate efficacy of this process of&#xD;
      care on patients' clinical outcomes&#xD;
&#xD;
      Scientific innovation The use of home based CD is rapidly growing and their contribution to&#xD;
      the diagnosis of Pex in CF patients deserves to be fully evaluated. The use of CUSUM is&#xD;
      particularly promising for monitoring indicators of CF PEx. Because CUSUM chart detects&#xD;
      rapidly changes in these indicators and can identify small persistent shifts, it can help to&#xD;
      trigger early treatment and reduce respiratory damages.&#xD;
&#xD;
      Furthermore, this is the first study which uses a combination of numerous CDs to evaluate&#xD;
      several warning indicators of PEx. In addition, putting patients at the center of their&#xD;
      health care and giving them more autonomy (empowerment) is innovative in this type of study&#xD;
      and can improve both detection and management of their PEx episodes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    recruitment and search completed&#xD;
  </why_stopped>
  <start_date type="Actual">October 20, 2017</start_date>
  <completion_date type="Actual">June 18, 2020</completion_date>
  <primary_completion_date type="Actual">June 18, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Prospective, multicenter, longitudinal pilot study on cohort, in 3 phases</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Exacerbations (ExR) concordance</measure>
    <time_frame>2 Years</time_frame>
    <description>Assesses agreement between the ExR episodes detected by the connected objects and the ExR episodes detected by the start date of the antibiotic treatment noted in the patient's medical record</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Hospital Anxiety and Depression scale (HADS)</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 22</time_frame>
    <description>Assesses anxiety and depressive disorders</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cystic Fibrosis Questionnaire-Revised (CFQ-R)</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 22</time_frame>
    <description>Assesses quality of live related to cystic fibrosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical data : FEV1</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses FEV1 (%) during a routine visit at the CF center</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical data: Weight</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses weight (kilograms) during a routine visit at the CF center</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical data: Height</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses height (meters) during a routine visit at the CF center</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical data: Heart rate</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses heart rate during a routine visit at the CF center</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical data: Oxygen saturation</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses oxygen saturation during a routine visit at the CF center</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : FEV1</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of FEV1 (%)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : Heart rate</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of heart rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : Oxygen saturation</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of oxygen saturation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : Weight</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of weight (kilograms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : Duration of sleep</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of duration of sleep</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physiological parameters with connected devices (PP) : Physical activity</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses with connected devices of physical activity (steps number)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceptions identified by patients (PRP)</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses by 1 questionnaire on connected devices of several illness perceptions (breathing difficulty ; need to intensify the physiotherapist ; increase in symptoms at night ; more sputum production ; increase in difficulty in daily activities ; tiredness ; reduction of appetite)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Traitements Number</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses number of antibiotic treatments prescribed during the study, collected from the data available in patient medical records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Traitements Duration</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses duration of antibiotic treatments prescribed during the study, collected from the data available in patient medical records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory symptoms</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses respiratory symptoms arising during the study, collected from the data available in patient medical records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exacerbations Number</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses number acute exacerbations arising, collected from the data available in patient medical records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exacerbations Timing</measure>
    <time_frame>Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22</time_frame>
    <description>Assesses timing of acute exacerbations arising, collected from the data available in patient medical records</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients and professionals interviews</measure>
    <time_frame>2 Years</time_frame>
    <description>Assesses experiences and frequency of use of connected devices: factors influencing the use of connected devices, trust and conviction in connected devices, impact on physician-patient relationship, impact of connected devices on daily lives...&#xD;
Semi-structured interviews will be conducted&#xD;
with the 30 patients: face to face or telephone&#xD;
with the 7 participating medical teams: face to face</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Cystic Fibrosis</condition>
  <arm_group>
    <arm_group_label>Refusal Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Refusal Questionnaires Intervention:&#xD;
Clinic staff will email all patients or parents (pediatric settings) to introduce the study. A qualitative interview with 10 patients who declined to participate in the study will be conducted to identify the reason of refusal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Interventionnal Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Connected Devices for 3 months (36 patients will be equipped with CDs-spirometer, oxymeter, scales, podometer watch and AURA device for sleep quality and analyze) Educationnal Intervention Connected Devices for 12 months Interviews</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Connected Devices for 3 months</intervention_name>
    <description>Inclusion will be proposed at a follow-up visit by the child's or adult's referring doctor. A written informed consent form will be obtained. Quality of Life and Anxiety-Depression will be collected. Then, each included patient will be equipped with CDs-spirometer, oxymeter, scale and watch during 3 months for base-line.</description>
    <arm_group_label>Interventionnal Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Educationnal Intervention</intervention_name>
    <description>After a first statistical analysis and interpretation (5 months), alert parameters for each patient are then fixed. An educational visit will be scheduled with patients and a personnalized action plan will be defined..</description>
    <arm_group_label>Interventionnal Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Connected Devices for 12 months</intervention_name>
    <description>Each included patient will be re-equipped with CDs-spirometer, oxymeter, scale and watch during 12 months. If alerts occur, patients will be informed by email or SMS, with data transmission to the medical team who will not interfere. Patients should apply the shared action plan they learned. Quality of Life and Anxiety-Depression will be collected.</description>
    <arm_group_label>Interventionnal Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Interviews</intervention_name>
    <description>At the end, semi-structured interviews will be completed to explore confidence on the CDs, impact on the doctor-patient relationship, change in the workload of medical team…etc.</description>
    <arm_group_label>Interventionnal Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Refusal Questionnaires</intervention_name>
    <description>Clinic staff will email all patients or parents (pediatric settings) to introduce the study. A qualitative interview with 10 patients who declined to participate in the study will be conducted to identify the reason of refusal</description>
    <arm_group_label>Refusal Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  12 years and over&#xD;
&#xD;
          -  Cystic fibrosis confirmed by sweat test or genetic&#xD;
&#xD;
          -  Able to understand and respect the protocol and its requirements&#xD;
&#xD;
          -  Who signed the consent prior to any other procedure protocolFollowed in the same CF&#xD;
             center during the study&#xD;
&#xD;
          -  In clinically stable condition - no pulmonary exacerbation requiring intravenous&#xD;
             antibiotics - in the previous 4 weeks)&#xD;
&#xD;
          -  Prescribed at least one pulmonary medication (eg, inhaled mucolytic, inhaled or oral&#xD;
             antibiotic therapy, hypertonic saline)&#xD;
&#xD;
          -  Not undergone solid organ transplants&#xD;
&#xD;
          -  With smartphone, computer or tablet connected to wifi access&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient undergoing solid organ transplant&#xD;
&#xD;
          -  Pregnancy or planned pregnancy during the period of the study&#xD;
&#xD;
          -  Patient on exclusion period because of other clinical research esearch&#xD;
&#xD;
          -  Patients who don't use connected devices during the 3 first months will be excluded&#xD;
             from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gilles RAULT, Ph</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondation Ildys</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CF adults center - Hopital Albert Calmette</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF adults center - Institut du Thorax</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF pediatrics center - Hopital Mère-Enfant</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF pediatrics center - Hopital Robert Debré</name>
      <address>
        <city>Paris</city>
        <zip>75019</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF adults and pediatrics center - American Memorial Hospital</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF adults and pediatrics center- Perharidy</name>
      <address>
        <city>Roscoff</city>
        <zip>29684</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CF pediatrics center - Hopital André Mignot</name>
      <address>
        <city>Versailles</city>
        <zip>78150</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 6, 2017</study_first_posted>
  <last_update_submitted>June 9, 2022</last_update_submitted>
  <last_update_submitted_qc>June 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Connected Devices</keyword>
  <keyword>Pulmonary Exacerbations</keyword>
  <keyword>Cumulative Sum (CUSUM) Chart</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cystic Fibrosis</mesh_term>
  </condition_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/NCT03304028
org study id: C16-119
secondary id: 2017-A00723-50
nct id: NCT03304028
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Early detection of pulmonary exacerbations (PEx) in Cystic Fibrosis (CF) patients is
      important to quickly trigger treatment and reduce respiratory damage. The investigators
      hypothesize that using home-based connected devices (CDs) in educated patients applying
      Cumulative sum charts (CUSUM) to monitor physiological parameters (PP) and patients'
      perception reported (PRP), will allow early detection of PEx.

      Objective: to study clinical validity of using CDs and evaluate adherence and satisfaction in
      CF patients and teams

      Design: 3 phase multicenter study in 36 CF patients aged >=12 years. Phase 1, patients are
      equipped during 3 months with CDs. PP and PRP to estimate CUSUM parameters are collected. In
      phase 2, patient's personalized educational plan to manage alerts is built. In phase 3, PP
      and PRP are collected during 12 months. Clinical validity, change in patients clinical data,
      quality of Life/Anxiety-Depression/Satisfaction, patients and teams' acceptance and adherence
      are assessed.
BACKGROUND

      Pulmonary exacerbations (PEx) are the major cause of lung function decline in Cystic Fibrosis
      (CF) patients leading to respiratory failure. Identifying warning signs of PEx is a priority
      to trigger early treatment and reduce respiratory damage. Some authors tried to define scores
      based on symptoms to standardize treatment. However, lack of consensus led the
      Euro-Care-CF-Working-Group to recommend the use of medical antibiotic treatment decision (or
      treatment modification) associated with PEx-like symptoms as best definition of PEx for
      clinical trials.

      A DELPHI study identified 10 signs frequently perceived by patients and 10 most often cited
      indicators by caregivers. Two studies have shown that a combination of physiological
      parameters (PP) and patient reported perceptions (PRP) such as weight loss, decreased
      spirometry , increased cough or increased sputum production reported daily, help diagnose PEx
      episodes and trigger early treatment. Clinical observations show that changes in PP and PRP
      related to PEx differ according to age and degree of lung function impairment. Currently,
      patients with CF do not routinely monitor their lung function at home, nor do they
      objectively track PP or PRP. Consequently, CF PEx can be diagnosed late when symptoms
      progress, in which they seek medical care. Thus, development of an effective approach that
      helps to monitor daily indicators of PEx to early identification and treatment is important.

        -  Home monitoring of PEx symptoms Several studies have been conducted with daily
           monitoring of PEx symptoms. Most of these studies monitored one or two respiratory
           parameters with data transmission to the medical staff who decide what course of action
           to take. In addition, these studies used for each parameter the same alert limit for all
           patients, as it is known that patients with CF have different thresholds of these
           indicators,some may present more frequently than others.

        -  CUSUM to monitor indicators of pulmonary exacerbation The use of statistical process
           control (SPC) shows promise for monitoring indicators of CF PEx and rapidly detecting
           unwanted changes in these indicators. SPC uses rigorous time-series analysis methods,
           with results reported as a graph of changes in indicators over time[9]. Moreover, SPC
           can help to determine whether these changes are real (related to a causative factor) or
           merely a manifestation of natural variability. Among SPC, cumulative sum (CUSUM) chart
           has been found effective for measuring and monitoring healthcare outcome. It detects
           changes rapidly, and can identify small shifts. Connected devices software programming
           integrating CUSUM alert limits can help to determine whether the changes in PP and PRT
           are due to real PEx episode.

      STUDY HYPOTHESIS The investigators hypothesize that using home-based CDs applying CUSUM with
      patient's personalized alert limits to monitor physiological data and PRP combined with
      patient education allows early detection of PEx. Studying alerts can help clinicians to
      develop a patient's personalized educational plan allowing patients better management of PEx
      including ability to make informed choices. This study aims to assess clinical validity of
      using different CDs, acceptance and adherence of patients of data collection of physiological
      data and PRPs, and acceptance by the clinical teams of this process of care. It will lead a
      larger trial aiming to evaluate efficacy of this process of care on patient's clinical
      outcomes.

      DESIGN

      Design: A 3 phase multi-center prospective longitudinal pilot study will be conducted.

      - Phase 1- Baseline data collection Clinic staff will email all patients or parents
      (pediatric settings) to introduce the study. A qualitative interview with 10 patients who
      declined to participate in the study will be conducted to identify the reason of refusal.

      M0: Inclusion visit: the inclusion will be proposed at a follow-up visit by the child's or
      adult's referring doctor. A written informed consent form will be obtained from all adults or
      both parents of children.

      Quality of Life and Anxiety-Depression will be collected using the HADS and CFQ-R scale Each
      included patient will be equipped with CDs-spirometer, oxymeter, scale and watch During 3
      months: Baseline data of 14 warning indicators of Pex will be collected during 3 non
      consecutive days a week using the CDs.

      Number and time of acute PEx, FEV1, weight, respiratory symptoms and antibiotic treatments
      prescribed will be collected at the end of the period from the medical patient chart in the
      CF centre.

        -  Phase 2- statistical analysis and patient education Statistical analysis of the data
           collected in phase 1 will take place to calculate the CUSUM parameters. Alert parameters
           for each patient are then fixed. An educational visit will be scheduled with patients

        -  Phase 3- CDs use and personalized care PP and PRP will be continuously collected during
           12 months using CDs. If alerts occur, patients will be informed by email or SMS, with
           data transmission to the medical team who will not interfere. Patients should apply the
           shared action plan they learned. Quality of Life and Anxiety-Depression will be
           collected using the HADS and CFQ-R scale. Number and time of acute PEx, FEV1, weight,
           respiratory symptoms and antibiotic treatments prescribed during the period will be
           collected at the end of the period from the medical patient chart in the CF centre.

      At the end of Phase 3: Semi-structured interviews will be completed with the 30
      patients/parents and 5 medical teams to explore confidence on the CDs, impact on the
      doctor-patient relationship, change in the workload of medical team…etc.

      EXPECTED RESULTS

      The investigators expect a better quality of life for patients, and that their
      anxiety-depression has not increased or rather decreased. For the clinical teams, the
      investigators aim to demonstrate that the use of CDs at home by educated patients is
      acceptable in their daily workload, and satisfying regarding the application of the shared
      action plan by the patient. Unlike other studies, patients are empowered to initiate actions
      when alerted by variations of the parameters. If they don't follow the action plan decided
      with the clinical teams, the treatment of PEx might not be earlier than if they didn't use
      CDs. In that case, a discussion with the clinicians may lead to the alternative process in
      which the alerts are used by the clinical teams to drive the actions for the patient.
      Interestingly, this alternative is possible because the alerts are simultaneously transmitted
      to the patient and to the team. The leader in the process may even change at some critical
      periods when the patient is in bad condition or depressed.

      Qualitative analysis will provide knowledge on benefits and pitfalls to improve confidence in
      the use of CDS at home from the patients and the clinical teams, improve the patient-team
      partnership and, decrease stress and anxiety about pulmonary exacerbation treatment. This
      study will lead to further plan a larger trial aiming to evaluate efficacy of this process of
      care on patients' clinical outcomes

      Scientific innovation The use of home based CD is rapidly growing and their contribution to
      the diagnosis of Pex in CF patients deserves to be fully evaluated. The use of CUSUM is
      particularly promising for monitoring indicators of CF PEx. Because CUSUM chart detects
      rapidly changes in these indicators and can identify small persistent shifts, it can help to
      trigger early treatment and reduce respiratory damages.

      Furthermore, this is the first study which uses a combination of numerous CDs to evaluate
      several warning indicators of PEx. In addition, putting patients at the center of their
      health care and giving them more autonomy (empowerment) is innovative in this type of study
      and can improve both detection and management of their PEx episodes.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, multicenter, longitudinal pilot study on cohort, in 3 phases
primary purpose: Prevention
masking: None (Open Label)
measure: Exacerbations (ExR) concordance
time frame: 2 Years
description: Assesses agreement between the ExR episodes detected by the connected objects and the ExR episodes detected by the start date of the antibiotic treatment noted in the patient's medical record
measure: Hospital Anxiety and Depression scale (HADS)
time frame: Inclusion ; month 3 ; month 10 ; month 22
description: Assesses anxiety and depressive disorders
measure: Cystic Fibrosis Questionnaire-Revised (CFQ-R)
time frame: Inclusion ; month 3 ; month 10 ; month 22
description: Assesses quality of live related to cystic fibrosis
measure: Medical data : FEV1
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses FEV1 (%) during a routine visit at the CF center
measure: Medical data: Weight
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses weight (kilograms) during a routine visit at the CF center
measure: Medical data: Height
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses height (meters) during a routine visit at the CF center
measure: Medical data: Heart rate
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses heart rate during a routine visit at the CF center
measure: Medical data: Oxygen saturation
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses oxygen saturation during a routine visit at the CF center
measure: Physiological parameters with connected devices (PP) : FEV1
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of FEV1 (%)
measure: Physiological parameters with connected devices (PP) : Heart rate
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of heart rate
measure: Physiological parameters with connected devices (PP) : Oxygen saturation
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of oxygen saturation
measure: Physiological parameters with connected devices (PP) : Weight
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of weight (kilograms)
measure: Physiological parameters with connected devices (PP) : Duration of sleep
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of duration of sleep
measure: Physiological parameters with connected devices (PP) : Physical activity
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses with connected devices of physical activity (steps number)
measure: Perceptions identified by patients (PRP)
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses by 1 questionnaire on connected devices of several illness perceptions (breathing difficulty ; need to intensify the physiotherapist ; increase in symptoms at night ; more sputum production ; increase in difficulty in daily activities ; tiredness ; reduction of appetite)
measure: Traitements Number
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses number of antibiotic treatments prescribed during the study, collected from the data available in patient medical records
measure: Traitements Duration
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses duration of antibiotic treatments prescribed during the study, collected from the data available in patient medical records
measure: Respiratory symptoms
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses respiratory symptoms arising during the study, collected from the data available in patient medical records
measure: Exacerbations Number
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses number acute exacerbations arising, collected from the data available in patient medical records
measure: Exacerbations Timing
time frame: Inclusion ; month 3 ; month 10 ; month 13 ; month 16 ; month 19 ; month 22
description: Assesses timing of acute exacerbations arising, collected from the data available in patient medical records
measure: Patients and professionals interviews
time frame: 2 Years
description: Assesses experiences and frequency of use of connected devices: factors influencing the use of connected devices, trust and conviction in connected devices, impact on physician-patient relationship, impact of connected devices on daily lives...
Semi-structured interviews will be conducted
with the 30 patients: face to face or telephone
with the 7 participating medical teams: face to face
arm group label: Refusal Group
arm group type: Other
description: Refusal Questionnaires Intervention:
Clinic staff will email all patients or parents (pediatric settings) to introduce the study. A qualitative interview with 10 patients who declined to participate in the study will be conducted to identify the reason of refusal.
arm group label: Interventionnal Group
arm group type: Other
description: Connected Devices for 3 months (36 patients will be equipped with CDs-spirometer, oxymeter, scales, podometer watch and AURA device for sleep quality and analyze) Educationnal Intervention Connected Devices for 12 months Interviews
intervention type: Device
intervention name: Connected Devices for 3 months
description: Inclusion will be proposed at a follow-up visit by the child's or adult's referring doctor. A written informed consent form will be obtained. Quality of Life and Anxiety-Depression will be collected. Then, each included patient will be equipped with CDs-spirometer, oxymeter, scale and watch during 3 months for base-line.
arm group label: Interventionnal Group
intervention type: Behavioral
intervention name: Educationnal Intervention
description: After a first statistical analysis and interpretation (5 months), alert parameters for each patient are then fixed. An educational visit will be scheduled with patients and a personnalized action plan will be defined..
arm group label: Interventionnal Group
intervention type: Device
intervention name: Connected Devices for 12 months
description: Each included patient will be re-equipped with CDs-spirometer, oxymeter, scale and watch during 12 months. If alerts occur, patients will be informed by email or SMS, with data transmission to the medical team who will not interfere. Patients should apply the shared action plan they learned. Quality of Life and Anxiety-Depression will be collected.
arm group label: Interventionnal Group
intervention type: Other
intervention name: Interviews
description: At the end, semi-structured interviews will be completed to explore confidence on the CDs, impact on the doctor-patient relationship, change in the workload of medical team…etc.
arm group label: Interventionnal Group
intervention type: Behavioral
intervention name: Refusal Questionnaires
description: Clinic staff will email all patients or parents (pediatric settings) to introduce the study. A qualitative interview with 10 patients who declined to participate in the study will be conducted to identify the reason of refusal
arm group label: Refusal Group
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Gilles RAULT, Ph
role: Principal Investigator
affiliation: Fondation Ildys
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Cystic Fibrosis
sharing ipd: No