<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/NCT02208817</url>
  </required_header>
  <id_info>
    <org_study_id>14021</org_study_id>
    <secondary_id>MRK0076101</secondary_id>
    <nct_id>NCT02208817</nct_id>
  </id_info>
  <brief_title>The Paediatric Refill Study (PRefill)</brief_title>
  <acronym>PRefill</acronym>
  <official_title>Development of a Novel Paediatric Continuous Early Warning Monitor for the Children at Risk of Respiratory and Cardiovascular Collapse - The Paediatric Refill Study (PRefill)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      2 recent national reports 'Why Children Die' and 'Are we there yet?'identified deficiencies&#xD;
      in recognising and managing sick children. Key recommendations from both reviews included the&#xD;
      development and adoption of 'track and trigger' or a paediatric early warning score (PEWS) to&#xD;
      better identify the sick or deteriorating child. PEWS tools offer the potential to identify&#xD;
      and respond sooner to clinical deterioration. Capillary refill time (CRT) is a measure of&#xD;
      skin blood flow and is a vital part of many early warning and resuscitation scores. It is a&#xD;
      sensitive marker of infection and dehydration in children. However, due to how it is&#xD;
      performed and interpreted CRT is prone to marked variability between observers.&#xD;
&#xD;
      We have Medical Research Council (MRC) funding to develop an automated capillary refill&#xD;
      device and user interface to provide a paediatric continuous early warning (PaedCEW)&#xD;
      monitoring system. The PaedCEW system would complement and support current clinical practice&#xD;
      and aim to address the difficulties of recognising ill children.&#xD;
&#xD;
      We aim to recruit 20 ill children on the Paediatric Intensive Care Unit (PICU) with 2 matched&#xD;
      controls without significant illness from the Nottingham Children's Hospital. The 20 ill&#xD;
      children will have their CRT (and PaedCEW score) monitored before, during and after admission&#xD;
      to PICU. This will allow correlation with invasive (BP, central venous oxygen saturations,&#xD;
      lactate) and noninvasive (CRT, heart rate, cardiac output) measures of cardiovascular status&#xD;
      during periods of stability and compromise. Matched controls will be monitored for around 24&#xD;
      hours. This pilot study will allow development of our system.&#xD;
&#xD;
      This is a proof of concept study. This study aims to demonstrate a novel device for measuring&#xD;
      CRT. Its correlation with noninvasive measures of cardiovascular status will enable a&#xD;
      pragmatic comparison with current clinical practice. In addition, correlation with invasive&#xD;
      measures of cardiovascular status will enable us to calculate sensitivity, specificity,&#xD;
      negative predictive value (NPV) and positive predictive value (PPV).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following recruitment, patients will have two devices placed on their skin, one on a limb&#xD;
      (e.g. forearm), and one on their chest. They will be fixed to the skin using medical adhesive&#xD;
      tape. The devices will be left on for around 1 hour on the &quot;well patients&quot; who are on a&#xD;
      general paediatric ward. At the end of this time a member of the research team will remove&#xD;
      the devices.&#xD;
&#xD;
      For patients going to the paediatric intensive care unit (PICU) the devices will be used to&#xD;
      gather the CRT data before admission (where possible), during and following discharge from&#xD;
      the PICU. The PICU participants will have the device left on during their stay, with the&#xD;
      agreement of the clinical team caring for the patient, with the device being resited every&#xD;
      4-6 hours as is normal practice for medical devices attached to the skin. Data will be&#xD;
      collected in this way during the PICU stay (which is typically 2-3 days) or until the patient&#xD;
      is transferred to the general ward. Before they go home, these participants will be monitored&#xD;
      again for up to an hour with the CRT devices to obtain data when they are well.&#xD;
&#xD;
      Collecting data in this way should allow us to show that our CRT device can detect a 30%&#xD;
      difference in perfusion between the well and the unwell patient. By comparing well patient to&#xD;
      unwell patient, and by comparing unwell patient, with themselves when well. For each&#xD;
      participant we will collect routine demographic details, medical history details, Fitzpatrick&#xD;
      skin colour assessment (that is their skin tone according to a recognised scale), height,&#xD;
      weight and vital signs. Where taken, we will collect clinically relevant data in relation to&#xD;
      the treatment received and results of clinical investigations for correlation with our device&#xD;
      data. Patients on the PICU will have noninvasive measures of perfusion performed by the&#xD;
      clinical team. The research team will also perform these at agreed times suitable to the care&#xD;
      of the patient. This will include capillary refill and ultrasound assessment of blood flow&#xD;
      (cardiac output).&#xD;
&#xD;
      We will also conduct a semistructured interview with the patient and/or their parents/carer&#xD;
      at the time of the study to gain feedback on the device. This should take about 15 minutes&#xD;
      and will take the form of a semistructured interview. We will also seek user (i.e. healthcare&#xD;
      professionals) feedback on the device and the accompanying GUI using a semistructured&#xD;
      interview (approximately 15 minutes).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Detect a 30% difference in measured CRT value between well children (PEWS &lt;3, with normal perfusion) and unwell children (PEWS ≥3, with reduced perfusion).</measure>
    <time_frame>Exit from study; Well patients within 1-2 hours; Unwell patients after leaving PICU average 3 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>i.Feedback on acceptability of the device from patients, carers/parents, and healthcare professionals, and feedback on the graphical user interface (GUI) from healthcare professionals.</measure>
    <time_frame>on completion of feedback, 30 minutes</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ii. Correlation of automated CRT results with vital cardiovascular clinical observations and tests - both invasive and non-invasive.</measure>
    <time_frame>During study phase average 3 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>iii. Correlation of automated CRT results with treatments supporting the cardiovascular and neurological system</measure>
    <time_frame>during study phase average 3 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRT in well compared with unwell patients</measure>
    <time_frame>Grouped at end of study 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRT changes with age and ethnicity in well children</measure>
    <time_frame>grouped at end of study 12 months</time_frame>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">75</enrollment>
  <condition>Septicaemia</condition>
  <condition>Deformity of Spine</condition>
  <condition>Trauma</condition>
  <arm_group>
    <arm_group_label>Ill patients</arm_group_label>
    <description>Ill patients who require Paediatric Intensive Care or Paediatric High Dependency Care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Well Controls</arm_group_label>
    <description>Matched controls who are well (PEWS&lt;3)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parent feedback</arm_group_label>
    <description>Feedback from parents/carers of children recruited into the PRefill study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthcare professionals feedback</arm_group_label>
    <description>Feedback from healthcare professionals who have cared for a child with the device on</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Children will be recruited in The Queens Medical Centre, Nottingham University Hospitals&#xD;
        NHS Trust, a teaching hospital, which has a paediatric intensive care unit (PICU).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children &amp; Young Adults&#xD;
&#xD;
          -  Patients aged 1 month to 15 years with parental or legal guardian written informed&#xD;
             consent.&#xD;
&#xD;
          -  Patients groups:&#xD;
&#xD;
          -  Patients who require PICU or high dependency care&#xD;
&#xD;
          -  Matched controls who are well (PEWS&lt;3)&#xD;
&#xD;
          -  Must have a realistic prospect of survival&#xD;
&#xD;
          -  Parents/carers (for the interview element of the study):&#xD;
&#xD;
          -  Parents/carers of children recruited into the PRefill study&#xD;
&#xD;
          -  Healthcare professionals (for the interview element of the study):&#xD;
&#xD;
          -  Healthcare professionals who have cared for a child with the device on&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children &amp; Young Adults&#xD;
&#xD;
          -  Known pregnancy&#xD;
&#xD;
          -  Underlying cardiac anomaly likely to affect perfusion,&#xD;
&#xD;
          -  PEWS ≥3 (in matched well controls)&#xD;
&#xD;
          -  Severe eczema/burns/other skin condition on site where CRT device needs to be&#xD;
             positioned&#xD;
&#xD;
          -  Known allergy to medical adhesive&#xD;
&#xD;
          -  Parents/carers (for the interview element of the study):&#xD;
&#xD;
          -  Unable to communicate despite translation services&#xD;
&#xD;
          -  Healthcare professionals (for the interview element of the study)&#xD;
&#xD;
          -  None&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>15 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Don Sharkey, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nottingham Univeristy Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <state>Nottinghamshire</state>
        <zip>NG72UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>May 18, 2016</last_update_submitted>
  <last_update_submitted_qc>May 18, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>capillary refill</keyword>
  <keyword>paediatric early warning score</keyword>
  <keyword>photoplethysmography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sepsis</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/NCT02208817
org study id: 14021
secondary id: MRK0076101
nct id: NCT02208817
lead sponsor: 
has dmc: No
2 recent national reports 'Why Children Die' and 'Are we there yet?'identified deficiencies
      in recognising and managing sick children. Key recommendations from both reviews included the
      development and adoption of 'track and trigger' or a paediatric early warning score (PEWS) to
      better identify the sick or deteriorating child. PEWS tools offer the potential to identify
      and respond sooner to clinical deterioration. Capillary refill time (CRT) is a measure of
      skin blood flow and is a vital part of many early warning and resuscitation scores. It is a
      sensitive marker of infection and dehydration in children. However, due to how it is
      performed and interpreted CRT is prone to marked variability between observers.

      We have Medical Research Council (MRC) funding to develop an automated capillary refill
      device and user interface to provide a paediatric continuous early warning (PaedCEW)
      monitoring system. The PaedCEW system would complement and support current clinical practice
      and aim to address the difficulties of recognising ill children.

      We aim to recruit 20 ill children on the Paediatric Intensive Care Unit (PICU) with 2 matched
      controls without significant illness from the Nottingham Children's Hospital. The 20 ill
      children will have their CRT (and PaedCEW score) monitored before, during and after admission
      to PICU. This will allow correlation with invasive (BP, central venous oxygen saturations,
      lactate) and noninvasive (CRT, heart rate, cardiac output) measures of cardiovascular status
      during periods of stability and compromise. Matched controls will be monitored for around 24
      hours. This pilot study will allow development of our system.

      This is a proof of concept study. This study aims to demonstrate a novel device for measuring
      CRT. Its correlation with noninvasive measures of cardiovascular status will enable a
      pragmatic comparison with current clinical practice. In addition, correlation with invasive
      measures of cardiovascular status will enable us to calculate sensitivity, specificity,
      negative predictive value (NPV) and positive predictive value (PPV).
Following recruitment, patients will have two devices placed on their skin, one on a limb
      (e.g. forearm), and one on their chest. They will be fixed to the skin using medical adhesive
      tape. The devices will be left on for around 1 hour on the "well patients" who are on a
      general paediatric ward. At the end of this time a member of the research team will remove
      the devices.

      For patients going to the paediatric intensive care unit (PICU) the devices will be used to
      gather the CRT data before admission (where possible), during and following discharge from
      the PICU. The PICU participants will have the device left on during their stay, with the
      agreement of the clinical team caring for the patient, with the device being resited every
      4-6 hours as is normal practice for medical devices attached to the skin. Data will be
      collected in this way during the PICU stay (which is typically 2-3 days) or until the patient
      is transferred to the general ward. Before they go home, these participants will be monitored
      again for up to an hour with the CRT devices to obtain data when they are well.

      Collecting data in this way should allow us to show that our CRT device can detect a 30%
      difference in perfusion between the well and the unwell patient. By comparing well patient to
      unwell patient, and by comparing unwell patient, with themselves when well. For each
      participant we will collect routine demographic details, medical history details, Fitzpatrick
      skin colour assessment (that is their skin tone according to a recognised scale), height,
      weight and vital signs. Where taken, we will collect clinically relevant data in relation to
      the treatment received and results of clinical investigations for correlation with our device
      data. Patients on the PICU will have noninvasive measures of perfusion performed by the
      clinical team. The research team will also perform these at agreed times suitable to the care
      of the patient. This will include capillary refill and ultrasound assessment of blood flow
      (cardiac output).

      We will also conduct a semistructured interview with the patient and/or their parents/carer
      at the time of the study to gain feedback on the device. This should take about 15 minutes
      and will take the form of a semistructured interview. We will also seek user (i.e. healthcare
      professionals) feedback on the device and the accompanying GUI using a semistructured
      interview (approximately 15 minutes).
observational model: Case-Control
time perspective: Prospective
measure: Detect a 30% difference in measured CRT value between well children (PEWS <3, with normal perfusion) and unwell children (PEWS ≥3, with reduced perfusion).
time frame: Exit from study; Well patients within 1-2 hours; Unwell patients after leaving PICU average 3 days
measure: i.Feedback on acceptability of the device from patients, carers/parents, and healthcare professionals, and feedback on the graphical user interface (GUI) from healthcare professionals.
time frame: on completion of feedback, 30 minutes
measure: ii. Correlation of automated CRT results with vital cardiovascular clinical observations and tests - both invasive and non-invasive.
time frame: During study phase average 3 days
measure: iii. Correlation of automated CRT results with treatments supporting the cardiovascular and neurological system
time frame: during study phase average 3 days
measure: CRT in well compared with unwell patients
time frame: Grouped at end of study 12 months
measure: CRT changes with age and ethnicity in well children
time frame: grouped at end of study 12 months
arm group label: Ill patients
description: Ill patients who require Paediatric Intensive Care or Paediatric High Dependency Care
arm group label: Well Controls
description: Matched controls who are well (PEWS<3)
arm group label: Parent feedback
description: Feedback from parents/carers of children recruited into the PRefill study
arm group label: Healthcare professionals feedback
description: Feedback from healthcare professionals who have cared for a child with the device on
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 1 Month
maximum age: 15 Years
healthy volunteers: No
last name: Don Sharkey, PhD
role: Principal Investigator
affiliation: University of Nottingham
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Sepsis