<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/NCT04431050</url>
  </required_header>
  <id_info>
    <org_study_id>19SM5486</org_study_id>
    <nct_id>NCT04431050</nct_id>
  </id_info>
  <brief_title>Evaluation of a Single Use Point of Care Device for the Diagnosis of Respiratory Pathogens</brief_title>
  <acronym>SIMPLIFI</acronym>
  <official_title>Evaluation of a Single Use Point of Care Device for the Diagnosis of Influenza and Other Respiratory Pathogens in Clinical Upper Airway Samples Using Isothermal Amplification - a Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sense Biodetection Limited</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Imperial College London</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>
      This study evaluates a single use point of care diagnostic test in the diagnosis of influenza&#xD;
      and other respiratory viral infections in adults. Participants will have a sample taken from&#xD;
      their nose using a swab. The swab will be gently mixed in a liquid solution which will then&#xD;
      be transferred into the device for testing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Influenza, commonly known as &quot;the flu&quot;, is an infectious disease caused by influenza viruses.&#xD;
&#xD;
      Influenza can contribute towards the development of pneumonia, sinus infections and worsening&#xD;
      of previous health problems such as asthma or heart failure. Healthy people can get very sick&#xD;
      from the flu and other respiratory viral infections and spread them to others. Therefore,&#xD;
      early detection is essential for the effective management of these infections. Infection&#xD;
      prevention and control measures including patient isolation, commencing anti-viral treatment&#xD;
      and whether or not hospital admission is required can all be positively influenced by the&#xD;
      rapid diagnosis of infection.&#xD;
&#xD;
      Current influenza testing can be performed by numerous methods. The gold standard is via&#xD;
      molecular assays including rapid molecular assays and reverse transcription polymerase chain&#xD;
      reaction (RT-PCR). Serological testing and antigen detection tests including&#xD;
      immunofluorescence assays are other methods but the sensitivity and specificity for these&#xD;
      tests are variable and tend to be lower than molecular testing methods.&#xD;
&#xD;
      In the United Kingdom (UK), influenza testing relies on clinical suspicion and the use of&#xD;
      respiratory viral PCR in the laboratory. The turn-around-time for this can still take upto 48&#xD;
      hours. Point of care (POC) testing has been considered by Public Health England, as platforms&#xD;
      with the potential to be used within 20 metres of patients and the results to be available&#xD;
      within 10 to 90 minutes. This new device is a true point of care test which can be performed&#xD;
      by the bedside with the results available within 10-15 mins.&#xD;
&#xD;
      This is a prospective single centre feasibility study carried out in an acute clinical&#xD;
      setting, the Accident and Emergency (A+E) department of Imperial College Healthcare National&#xD;
      Health Service (NHS) Trust (ICHNT).&#xD;
&#xD;
      The primary objective is to assess the feasibility of this novel single use product for the&#xD;
      diagnosis of influenza and other respiratory pathogens in upper airway samples at the POC in&#xD;
      acute clinical settings and compare the results against the conventional diagnostic methods&#xD;
      of PCR testing in the laboratory and or rapid flu testing (Cepheid, Sunnyvale, CA, USA).&#xD;
      While the secondary objective is to compare the results obtained in a clinical setting to the&#xD;
      analytical study data and laboratory test on stored samples. A further objective is to&#xD;
      develop a bank of research samples for further testing of the device in laboratory&#xD;
      conditions. Sensitivity, specificity, positive predictive value and negative predictive value&#xD;
      of the new POC device in fresh samples will be calculated and compared to the results on&#xD;
      stored samples.&#xD;
&#xD;
      The patient will be seen in the clinical setting on a one off visit. Any adult presenting&#xD;
      with Influenza Like Illness or a febrile illness associated with symptoms such as cough, sore&#xD;
      throat or rhinorrhoea, and for whom a respiratory viral screen is clinically indicated will&#xD;
      be recruited if they meet the eligibility criteria.&#xD;
&#xD;
      Consent will be taken by a qualified doctor, member of the local clinical care team, a&#xD;
      research nurse or clinical fellow.&#xD;
&#xD;
      Participants will also be provided with contact details of the study co-ordination centre for&#xD;
      future queries.&#xD;
&#xD;
      One nasal swab will be taken per patient recruited in addition to the swab(s) (nasal,&#xD;
      nasopharyngeal or throat swab) taken for standard care. The routine screening sample(s)&#xD;
      (Sample A) will be processed for standard PCR testing in the laboratory and/or rapid flu&#xD;
      testing (Cepheid, Sunnyvale, CA, USA) as per standard clinical screening. The test sample&#xD;
      (Sample B) will be taken for evaluation under the study and either: (i) transferred to the&#xD;
      new device buffer tube and promptly tested in a test device or (ii) if no device is available&#xD;
      for prompt testing, the swab will be transferred to a viral storage/transport buffer tube as&#xD;
      per standard procedures and frozen for long-term storage and testing at a later date.&#xD;
&#xD;
      The swab will be rotated up to 5 times and held in place for 5-10 seconds. The swab will then&#xD;
      be inserted into the single-use elution buffer tube containing the elution buffer and stirred&#xD;
      5 times. The swab will then be safely discarded in clinical waste. A volume of 200ul of&#xD;
      buffer will then be transferred to the sample chamber of the device using the fixed volume&#xD;
      pipette provided. The assay will be performed according to the 'Instructions for Use'&#xD;
      provided with the device. Results require no calibration, interpretation, or calculation. The&#xD;
      total time to result is expected to be approximately 10 minutes. The pathogens which will be&#xD;
      tested in the test device include one or more of the following: influenza A, influenza B,&#xD;
      respiratory syncytial virus, human rhinovirus/enterovirus, human metapneumovirus and&#xD;
      parainfluenza viruses.&#xD;
&#xD;
      All tests performed on the device will be performed 'blinded', i.e. the operator will be&#xD;
      unaware of the diagnostic standard of care result to ensure reading of results are not based&#xD;
      upon results obtained with standard tests. The test result will not be disclosed to either&#xD;
      the patient or the clinician. Each patient will be expected to participate for a total of 30&#xD;
      minutes.&#xD;
&#xD;
      As this is a feasibility study, diagnostic standard of care tests will be performed as per&#xD;
      the clinical pathway with routine sample(s) (A) and the results of the test devices will not&#xD;
      affect clinical decisions.&#xD;
&#xD;
      A minimum of 50 devices will be tested with fresh patient samples in a real life clinical&#xD;
      setting. Opportunistic patient samples will be collected and banked throughout the study&#xD;
      period. The aim will be to recruit as many patients as possible. A target of 200 patients has&#xD;
      been set based on 1600 viral PCRs taken at ICHNT last year over the influenza period and a&#xD;
      realistic estimate was made for the sample size for patients who may be willing to&#xD;
      participate in the study presenting with Influenza Like Illness, with consideration of time&#xD;
      and resource constraints. This data will be analysed to review the feasibility of this new&#xD;
      device.&#xD;
&#xD;
      Medical and demographic data will be collected during the study and documented on the&#xD;
      following case report forms (CRFs).&#xD;
&#xD;
        -  Baseline CRF - Including demographic information, medical history, symptoms, signs and&#xD;
           observations at the time of recruitment&#xD;
&#xD;
        -  Results CRF - Including results from the POC device, how many devices were required to&#xD;
           obtain a results, any issues with the device, results of the standard viral PCR results,&#xD;
           patient outcomes and use of anti-viral treatment.&#xD;
&#xD;
      Additional data will be collected where required using the following CRFs:&#xD;
&#xD;
        -  Adverse Events/Serious Adverse Events CRF.&#xD;
&#xD;
        -  Withdrawal CRF - to be completed if patient withdraws consent. This data will be&#xD;
           collected by a clinical research fellow or research nurses using participant hospital&#xD;
           records or from the participant directly. In addition, pseudo-anonymised test results&#xD;
           and imaging reports maybe collected. This could include but will not be limited to X-ray&#xD;
           reports, CT scan reports, and pathology reports.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 24, 2020</start_date>
  <completion_date type="Anticipated">April 30, 2021</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assessing the feasibility of a single use diagnostic point of care test against standard care testing methods, in a real-life clinical setting.</measure>
    <time_frame>through study completion, an average of 1.5 years</time_frame>
    <description>The primary outcome will be to review the feasibility and the diagnostic accuracy for viral respiratory pathogens in this novel device using fresh patients' samples in a real-life clinical setting compared to the standard diagnostic testing of a respiratory viral PCR in the laboratory and/or rapid flu swab (Cepheid, Sunnyvale, CA, USA) using sensitivity, specificity, positive predictive value and negative predictive values. A minimum of 50 devices will be tested with fresh patient samples in a real life clinical setting.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare the results obtained in a clinical setting to the analytical study data and laboratory tests on stored samples.</measure>
    <time_frame>through study completion, an average of 1.5 years</time_frame>
    <description>The secondary outcome will be to review the feasibility and the diagnostic accuracy for viral respiratory pathogens in this novel device using patients' stored samples in a laboratory setting compared to the standard diagnostic testing of a respiratory viral PCR in the laboratory and/or rapid flu swab (Cepheid, Sunnyvale, CA, USA) using sensitivity, specificity, positive predictive value and negative predictive values.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Human Influenza</condition>
  <condition>Respiratory Syncytial Virus Infections</condition>
  <condition>Rhinoviral Infections</condition>
  <condition>Enterovirus Infections</condition>
  <condition>Metapneumovirus Infection</condition>
  <condition>Parainfluenzae Viral Infections</condition>
  <arm_group>
    <arm_group_label>Suspected influenza or other respiratory viral infection.</arm_group_label>
    <description>Any adult presenting to the Accident &amp; Emergency department with influenza like illness or a febrile illness associated with symptoms such as cough, sore throat or rhinorrhoea, and for whom a respiratory viral screen is clinically indicated.&#xD;
For the purposes of this study one nasal swab will be taken from consenting adults.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Point of care testing of respiratory viruses.</intervention_name>
    <description>Single use point of care diagnostic device.</description>
    <arm_group_label>Suspected influenza or other respiratory viral infection.</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      One nasal swab taken from each participant for diagnostics.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Any consenting adult presenting to the Accident and Emergency department with influenza&#xD;
        like illness or a febrile illness associated with symptoms such as cough, sore throat or&#xD;
        rhinorrhoea, and for whom a respiratory viral screen is clinically indicated will be&#xD;
        recruited.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Any adult ≥18 years of age presenting to the A+E department with ILI or a febrile illness&#xD;
        associated with symptoms such as cough, sore throat or rhinorrhoea, and for whom a&#xD;
        respiratory viral screen is clinically indicated and who is:&#xD;
&#xD;
          -  Able to provide written informed consent, or written informed assent by a relative or&#xD;
             carer&#xD;
&#xD;
          -  Recruited during initial medical assessment&#xD;
&#xD;
          -  Able to comply with the study protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previously recruited within 28 days of the current admission&#xD;
&#xD;
          -  Enrolment in a trial of antimicrobial therapy&#xD;
&#xD;
          -  If patients are unable to understand verbal or written information in English,&#xD;
             hospital translation services will be sought but not guaranteed. However, if the team&#xD;
             member seeking consent is not satisfied that the potential recruits' English language&#xD;
             ability is sufficient to completely understand the study protocol and requirements&#xD;
             (despite use of hospital translation services) then they will not be recruited to the&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Muir</last_name>
    <role>Principal Investigator</role>
    <affiliation>Imperial College Healthcare NHS Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sean O Riordan</last_name>
    <phone>0044 2033125730</phone>
    <email>sean.oriordan@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mirae Park</last_name>
    <phone>0044 2033125730</phone>
    <email>mirae.park@nhs.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Imperial College Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>David Muir</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>February 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 10, 2020</last_update_submitted>
  <last_update_submitted_qc>June 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Influenza, Human</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Respiratory Syncytial Virus Infections</mesh_term>
    <mesh_term>Enterovirus Infections</mesh_term>
    <mesh_term>Paramyxoviridae Infections</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/NCT04431050
org study id: 19SM5486
nct id: NCT04431050
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study evaluates a single use point of care diagnostic test in the diagnosis of influenza
      and other respiratory viral infections in adults. Participants will have a sample taken from
      their nose using a swab. The swab will be gently mixed in a liquid solution which will then
      be transferred into the device for testing.
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses.

      Influenza can contribute towards the development of pneumonia, sinus infections and worsening
      of previous health problems such as asthma or heart failure. Healthy people can get very sick
      from the flu and other respiratory viral infections and spread them to others. Therefore,
      early detection is essential for the effective management of these infections. Infection
      prevention and control measures including patient isolation, commencing anti-viral treatment
      and whether or not hospital admission is required can all be positively influenced by the
      rapid diagnosis of infection.

      Current influenza testing can be performed by numerous methods. The gold standard is via
      molecular assays including rapid molecular assays and reverse transcription polymerase chain
      reaction (RT-PCR). Serological testing and antigen detection tests including
      immunofluorescence assays are other methods but the sensitivity and specificity for these
      tests are variable and tend to be lower than molecular testing methods.

      In the United Kingdom (UK), influenza testing relies on clinical suspicion and the use of
      respiratory viral PCR in the laboratory. The turn-around-time for this can still take upto 48
      hours. Point of care (POC) testing has been considered by Public Health England, as platforms
      with the potential to be used within 20 metres of patients and the results to be available
      within 10 to 90 minutes. This new device is a true point of care test which can be performed
      by the bedside with the results available within 10-15 mins.

      This is a prospective single centre feasibility study carried out in an acute clinical
      setting, the Accident and Emergency (A+E) department of Imperial College Healthcare National
      Health Service (NHS) Trust (ICHNT).

      The primary objective is to assess the feasibility of this novel single use product for the
      diagnosis of influenza and other respiratory pathogens in upper airway samples at the POC in
      acute clinical settings and compare the results against the conventional diagnostic methods
      of PCR testing in the laboratory and or rapid flu testing (Cepheid, Sunnyvale, CA, USA).
      While the secondary objective is to compare the results obtained in a clinical setting to the
      analytical study data and laboratory test on stored samples. A further objective is to
      develop a bank of research samples for further testing of the device in laboratory
      conditions. Sensitivity, specificity, positive predictive value and negative predictive value
      of the new POC device in fresh samples will be calculated and compared to the results on
      stored samples.

      The patient will be seen in the clinical setting on a one off visit. Any adult presenting
      with Influenza Like Illness or a febrile illness associated with symptoms such as cough, sore
      throat or rhinorrhoea, and for whom a respiratory viral screen is clinically indicated will
      be recruited if they meet the eligibility criteria.

      Consent will be taken by a qualified doctor, member of the local clinical care team, a
      research nurse or clinical fellow.

      Participants will also be provided with contact details of the study co-ordination centre for
      future queries.

      One nasal swab will be taken per patient recruited in addition to the swab(s) (nasal,
      nasopharyngeal or throat swab) taken for standard care. The routine screening sample(s)
      (Sample A) will be processed for standard PCR testing in the laboratory and/or rapid flu
      testing (Cepheid, Sunnyvale, CA, USA) as per standard clinical screening. The test sample
      (Sample B) will be taken for evaluation under the study and either: (i) transferred to the
      new device buffer tube and promptly tested in a test device or (ii) if no device is available
      for prompt testing, the swab will be transferred to a viral storage/transport buffer tube as
      per standard procedures and frozen for long-term storage and testing at a later date.

      The swab will be rotated up to 5 times and held in place for 5-10 seconds. The swab will then
      be inserted into the single-use elution buffer tube containing the elution buffer and stirred
      5 times. The swab will then be safely discarded in clinical waste. A volume of 200ul of
      buffer will then be transferred to the sample chamber of the device using the fixed volume
      pipette provided. The assay will be performed according to the 'Instructions for Use'
      provided with the device. Results require no calibration, interpretation, or calculation. The
      total time to result is expected to be approximately 10 minutes. The pathogens which will be
      tested in the test device include one or more of the following: influenza A, influenza B,
      respiratory syncytial virus, human rhinovirus/enterovirus, human metapneumovirus and
      parainfluenza viruses.

      All tests performed on the device will be performed 'blinded', i.e. the operator will be
      unaware of the diagnostic standard of care result to ensure reading of results are not based
      upon results obtained with standard tests. The test result will not be disclosed to either
      the patient or the clinician. Each patient will be expected to participate for a total of 30
      minutes.

      As this is a feasibility study, diagnostic standard of care tests will be performed as per
      the clinical pathway with routine sample(s) (A) and the results of the test devices will not
      affect clinical decisions.

      A minimum of 50 devices will be tested with fresh patient samples in a real life clinical
      setting. Opportunistic patient samples will be collected and banked throughout the study
      period. The aim will be to recruit as many patients as possible. A target of 200 patients has
      been set based on 1600 viral PCRs taken at ICHNT last year over the influenza period and a
      realistic estimate was made for the sample size for patients who may be willing to
      participate in the study presenting with Influenza Like Illness, with consideration of time
      and resource constraints. This data will be analysed to review the feasibility of this new
      device.

      Medical and demographic data will be collected during the study and documented on the
      following case report forms (CRFs).

        -  Baseline CRF - Including demographic information, medical history, symptoms, signs and
           observations at the time of recruitment

        -  Results CRF - Including results from the POC device, how many devices were required to
           obtain a results, any issues with the device, results of the standard viral PCR results,
           patient outcomes and use of anti-viral treatment.

      Additional data will be collected where required using the following CRFs:

        -  Adverse Events/Serious Adverse Events CRF.

        -  Withdrawal CRF - to be completed if patient withdraws consent. This data will be
           collected by a clinical research fellow or research nurses using participant hospital
           records or from the participant directly. In addition, pseudo-anonymised test results
           and imaging reports maybe collected. This could include but will not be limited to X-ray
           reports, CT scan reports, and pathology reports.
observational model: Cohort
time perspective: Cross-Sectional
measure: Assessing the feasibility of a single use diagnostic point of care test against standard care testing methods, in a real-life clinical setting.
time frame: through study completion, an average of 1.5 years
description: The primary outcome will be to review the feasibility and the diagnostic accuracy for viral respiratory pathogens in this novel device using fresh patients' samples in a real-life clinical setting compared to the standard diagnostic testing of a respiratory viral PCR in the laboratory and/or rapid flu swab (Cepheid, Sunnyvale, CA, USA) using sensitivity, specificity, positive predictive value and negative predictive values. A minimum of 50 devices will be tested with fresh patient samples in a real life clinical setting.
measure: To compare the results obtained in a clinical setting to the analytical study data and laboratory tests on stored samples.
time frame: through study completion, an average of 1.5 years
description: The secondary outcome will be to review the feasibility and the diagnostic accuracy for viral respiratory pathogens in this novel device using patients' stored samples in a laboratory setting compared to the standard diagnostic testing of a respiratory viral PCR in the laboratory and/or rapid flu swab (Cepheid, Sunnyvale, CA, USA) using sensitivity, specificity, positive predictive value and negative predictive values.
arm group label: Suspected influenza or other respiratory viral infection.
description: Any adult presenting to the Accident & Emergency department with influenza like illness or a febrile illness associated with symptoms such as cough, sore throat or rhinorrhoea, and for whom a respiratory viral screen is clinically indicated.
For the purposes of this study one nasal swab will be taken from consenting adults.
intervention type: Diagnostic Test
intervention name: Point of care testing of respiratory viruses.
description: Single use point of care diagnostic device.
arm group label: Suspected influenza or other respiratory viral infection.
One nasal swab taken from each participant for diagnostics.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Muir
role: Principal Investigator
affiliation: Imperial College Healthcare NHS Trust
last name: Sean O Riordan
phone: 0044 2033125730
email: sean.oriordan@nhs.net
last name: Mirae Park
phone: 0044 2033125730
email: mirae.park@nhs.net
facility: 
status: Recruiting
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Influenza, Human
mesh term: Virus Diseases
mesh term: Respiratory Syncytial Virus Infections
mesh term: Enterovirus Infections
mesh term: Paramyxoviridae Infections