<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/NCT03840395</url>
  </required_header>
  <id_info>
    <org_study_id>AHE-06</org_study_id>
    <nct_id>NCT03840395</nct_id>
  </id_info>
  <brief_title>The PhINEST Study - Pharyngeal ICU Novel Electrical Stimulation Therapy</brief_title>
  <acronym>PhINEST</acronym>
  <official_title>The PhINEST Study - Pharyngeal ICU Novel Electrical Stimulation Therapy: a Prospective, Multi-site, Randomised, Sham-controlled, Single-blind (Outcome Assessor-blinded) Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Phagenesis Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NAMSA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cytel Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Phagenesis Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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 is a prospective, multi-site, randomised, sham-controlled, single-blind (outcome&#xD;
      assessor-blinded) study designed to assess the effects of Pharyngeal Electrical Stimulation&#xD;
      (PES) (using Phagenyx®) for the treatment of oropharyngeal dysphagia after invasive&#xD;
      mechanical ventilation (of any duration) by means of naso or oro-tracheal tube in critically&#xD;
      ill intensive care unit (ICU) patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The PhINEST study is designed to assess the effects of Pharyngeal Electrical Stimulation&#xD;
      (PES) (using Phagenyx®) for treatment of oropharyngeal dysphagia after invasive mechanical&#xD;
      ventilation (of any duration) by means of naso or oro-tracheal tube in critically ill&#xD;
      intensive care unit (ICU) patients.&#xD;
&#xD;
      The main clinical outcomes assessing unsafe swallows and dysphagia severity will be measured&#xD;
      using the gold standard, i.e. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and&#xD;
      bedside swallowing assessments on day 2* after completion of final PES treatment.&#xD;
&#xD;
      Randomisation will be on a 1:1 basis at each site stratified for neurological vs.&#xD;
      non-neurological reason for admission (Acute Physiology and Chronic Health Evaluation&#xD;
      (APACHE) IV diagnostic group). Patients will receive either PES/sham treatment in addition to&#xD;
      standard supportive ICU care and standard of care treatments for dysphagia. Administration of&#xD;
      all protocol-specific assessments will be conducted by personnel blinded to treatment&#xD;
      assignment.&#xD;
&#xD;
      The study will follow an adaptive population enrichment and sample size re-estimation (SSR)&#xD;
      design with one interim look. The study will start with a planned sample size of 200 patients&#xD;
      and a maximum (evaluable) sample size of 360. Interim analysis after completion of&#xD;
      approximately 140 (evaluable) patients will determine:&#xD;
&#xD;
      I. futility stopping; OR II. sample size increase for the overall sampled population; OR III.&#xD;
      Enrichment based on the composite primary endpoint by pre-defined subgroups (neurological vs.&#xD;
      non-neurological reason for admission according to APACHE IV diagnostic groups). Thus&#xD;
      enrollment of patients in the non-performing sub-group will be stopped at the interim while a&#xD;
      sample-size re-estimation based on conditional power will be carried out for the other&#xD;
      sub-group.&#xD;
&#xD;
      All interim decisions will be based on conditional power which for the Finkelstein-Schoenfeld&#xD;
      (FS)-statistic will need to be computed via Monte-Carlo simulations.&#xD;
&#xD;
      Up to thirty (30) investigational sites across Europe are planned to participate in this&#xD;
      study which is expected to last 48 months from first patient first visit to last patient last&#xD;
      visit. Patients will be assessed at the following intervals: screening, baseline, on day 2*&#xD;
      after completion of final study treatment, 7 ± 1 days after final study treatment and 14 ± 1&#xD;
      days after final study treatment (or hospital discharge if earlier). 30-day and 90-day&#xD;
      mortality data will also be collected from the patients medical notes/electronic heath&#xD;
      records/telephone call (no additional visit required).&#xD;
&#xD;
      *The day two (FU1) visit is to be conducted on the second day (~24hrs) following final PES&#xD;
      treatment but may, under certain circumstances, be conducted upon/by the fourth day (~60 hrs)&#xD;
      following final study treatment in instances where the final study treatment is delivered on&#xD;
      late Friday and where FEES assessment is only possible early on Monday as no weekend FEES&#xD;
      service is available at the investigation site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 17, 2019</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effectiveness of Phagenyx® treatment in reducing severity of unsafe swallows - Penetration-Aspiration Scale (PAS) Scores</measure>
    <time_frame>Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment</time_frame>
    <description>Analysis of a two endpoints composite (FS-statistic) on a hierarchy of clinical priorities:&#xD;
Endpoint 1 - Swallowing safety based on worst PAS score in up to 4 thin (water) boli for each patient during FEES assessment converted to a trichotomised ordinal response of safe (PAS 1-3), penetration (PAS 4-5), or aspiration (PAS 6-8).&#xD;
The PAS provides a scoring system for airway closure and clearance during FEES. The PAS is a validated 8-point scale quantifying penetration and aspiration events primarily by the depth to which material passes into the airway and whether or not it is ejected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effectiveness of Phagenyx® treatment in reducing the severity of unsafe swallows - Dysphagia Outcome and Severity Score (DOSS) score</measure>
    <time_frame>7±1 days after the final Phagenyx® treatment</time_frame>
    <description>Analysis of a two endpoints composite (FS-statistic) on a hierarchy of clinical priorities:&#xD;
Endpoint 2 - DOSS scale score determined by bedside assessment.&#xD;
The DOSS is a simple, easy-to-use, 7-point scale developed to systematically rate the functional severity of dysphagia based on objective assessment and make recommendations for diet level, independence level, and type of nutrition.&#xD;
Severe dysphagia&#xD;
Moderately severe dysphagia&#xD;
Moderate dysphagia&#xD;
Mild-moderate dysphagia&#xD;
Mild dysphagia&#xD;
Functional limitation and modified independence&#xD;
Normal in all situations</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment in improving DOSS score.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by the DOSS score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on time from to feeding tube removal.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by time from randomisation to removal of feeding tube.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on time to oral intake.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by time to oral intake (if applicable).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on total days of enteral feeding.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by total days of enteral feeding.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment in improving Functional Oral Intake Scale (FOIS) score.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by the FOIS score.&#xD;
The FOIS provides a scoring system to document the functional level of oral intake of food and liquid in patients with dysphagia. It is a validated 7-point ordinal scale easily completed from information contained in medical charts, dietary journals, and/or patient reports.&#xD;
Nothing by mouth&#xD;
Tube dependent with minimal attempts of food or liquid&#xD;
Tube dependent with consistent intake of liquid or food&#xD;
Total oral diet of a single consistency&#xD;
Total oral diet with multiple consistencies but requiring special preparation or compensations&#xD;
Total oral diet with multiple consistencies without special preparation, but with specific food limitations&#xD;
Total oral diet with no restriction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment in improving Dysphagia Severity Rating Scale (DSRS) score.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Changes in nutritional management and severity of dysphagia as measured by the DSRS score.&#xD;
The DSRS is a simple to use, validated 13-point scale composed of a 3-component score that includes feeding independence, but nutrition level and diet modification is split into the components of liquid feeding and overall diet consistency. The DSRS is the sum of the scores of each of the 3 individual components (range 0-4 for each component) rather than a combination of the three components into an ordinal scale.&#xD;
Best score = 0 (no dysphagia) Worst score = 12 (NPO)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on time from extubation to ICU discharge</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>General health outcome measured by time from extubation to ICU discharge (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on length of stay in ICU</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>General health outcome measured by length of stay in ICU (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on length of stay in hospital.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>General health outcome measured by length of stay in hospital (days).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on number of patients with re-intubation during hospital stay</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>General health outcome measured by number of patients with re-intubation during hospital stay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effectiveness of Phagenyx® treatment on mortality</measure>
    <time_frame>Up to 90 days after completion of the final Phagenyx® treatment.</time_frame>
    <description>General health outcome measured by 30-day and 90-day mortality.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment in reducing (dysphagia) secretion severity.</measure>
    <time_frame>Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment</time_frame>
    <description>Exploratory analysis of changes in secretion severity (severity of dysphagia) between FEES assessments measured by an Independent FEES Review Committee (IFRC) using the Murray Secretion Severity Rating Scale (SSS).&#xD;
The SSS is a simple, easy-to-use, 4-point scale that can systematically rate the graduation of accumulated secretions within the pharyngolarynx and trachea during FEES.&#xD;
0. Normal&#xD;
Mild&#xD;
Moderate&#xD;
Severe</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment in improving swallowing safety and efficiency - PAS scores</measure>
    <time_frame>Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment</time_frame>
    <description>Exploratory analysis of changes in swallowing safety and efficiency (severity of dysphagia) between FEES assessments measured by an IFRC based on worst PAS score for each bolus consistency (semi-solid and solid) for each patient during FEES assessment converted to a dichotomised ordinal response of non-aspirator (PAS 1-5) or aspirator (PAS 6-8).</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment in reducing bolus residue</measure>
    <time_frame>Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment</time_frame>
    <description>Exploratory analysis of changes in bolus residue (severity of dysphagia) between FEES assessments measured by an IFRC using the Yale Pharyngeal Residue Severity Rating Scale (YRS).&#xD;
The YRS is a reliable, validated, anatomically defined, and image-based five-point ordinal rating scale to determine severity of post-swallow pharyngeal residue location (vallecula and pyriform sinus) and amount (i. none, ii. trace, iii. mild, iv. moderate, and v. severe) during FEES.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment in reducing global dysphagia severity</measure>
    <time_frame>Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment</time_frame>
    <description>Exploratory analysis of changes in severity of dysphagia between FEES assessments measured by an IFRC using the Global Dysphagia Severity Rating Scale (GDS).&#xD;
The GDS is a simple, easy-to-use, 4-point scale developed to systematically rate the severity of dysphagia during FEES.&#xD;
0. No relevant dysphagia&#xD;
Mild dysphagia: Premature spillage and/or residues, but no penetration/aspiration events.&#xD;
Moderate dysphagia: Penetration/aspiration events with one consistency.&#xD;
Severe dysphagia: Penetration/aspiration events with two or more consistencies.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on time from extubation to hospital discharge</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Exploratory analysis of general health outcome measured by time from extubation to hospital discharge (days).</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on days on antimicrobials post-extubation (while in ICU)</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Exploratory analysis of general health outcome measured by days on antimicrobials post-extubation (while in ICU).</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on hospital discharge destination</measure>
    <time_frame>Up to 90 days after the final Phagenyx® treatment</time_frame>
    <description>Exploratory analysis of general health outcome measured by hospital discharge destination (home, home+care, nursing home, other hospital, rehabilitation centre).</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on ICU readmission rate during hospital stay</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Exploratory analysis of general health outcome measured by ICU readmission rate during hospital stay.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on tracheostomies per subgroup</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Exploratory analysis of general health outcome measured by number of and reason for tracheostomies per subgroup after PES-treatment during hospital stay.</description>
  </other_outcome>
  <other_outcome>
    <measure>Effectiveness of Phagenyx® treatment on chest X-rays for suspected pneumonia.</measure>
    <time_frame>Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).</time_frame>
    <description>Exploratory analysis of general health outcome measured by total number of chest X-rays during hospital stay after ICU discharge for suspected pneumonia.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">360</enrollment>
  <condition>Dysphagia</condition>
  <arm_group>
    <arm_group_label>Active PES</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to receive active Pharyngeal Electrical Stimulation (PES) via a Phagenyx Catheter.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham PES</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients randomized to sham will not receive any Pharyngeal Electrical Stimulation (PES) but will still have the Phagenyx Catheter inserted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Pharyngeal Electrical Stimulation (PES)</intervention_name>
    <description>The Phagenyx® system is a two-part neurostimulation system. It is composed of a durable component called the Base Station and the single-use sterile disposable Catheter. The Base Station acts as the user interface and provides the means to generate, optimize and monitor the delivery of electrical stimulation to the oropharynx. The Phagenyx® devices are CE labelled (2012) and will be used in accordance with their intended use label.</description>
    <arm_group_label>Active PES</arm_group_label>
    <arm_group_label>Sham PES</arm_group_label>
    <other_name>Phagenyx</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Pre-screening Inclusion Criteria:&#xD;
&#xD;
        All of the following criteria must be met for inclusion:&#xD;
&#xD;
          -  Age ≥ 18 ≤ 85,&#xD;
&#xD;
          -  Emergency ICU admission (unplanned admission),&#xD;
&#xD;
          -  Recent extubation following invasive mechanical ventilation (of any length of time) by&#xD;
             means of endotracheal tube,&#xD;
&#xD;
          -  Presence of post-extubation dysphagia as determined by the participating Sites'&#xD;
             Standard Of Care (SOC).&#xD;
&#xD;
        Screening / Enrolment Criteria:&#xD;
&#xD;
        To be eligible for enrolment in this study, an individual must meet all of the following&#xD;
        additional criteria:&#xD;
&#xD;
          -  Presence of written informed consent according to respective national guidelines,&#xD;
&#xD;
          -  Dysphagia severity status classified according to PAS on FEES assessment as&#xD;
             'aspiration' (PAS score ≥ 6),&#xD;
&#xD;
          -  Richmond Agitation and Sedation Scale (RASS) score within the range of -1 to +2 (i.e.&#xD;
             if score equals -2, -3, -4 or +3, +4, patient is excluded).&#xD;
&#xD;
        Randomisation Inclusion Criteria (post-consent)&#xD;
&#xD;
        The following additional criteria must be met for randomisation:&#xD;
&#xD;
        • Successful placement and subjective tolerance of the Phagenyx® Catheter within 2 days of&#xD;
        extubation.(post consent)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        An individual who meets any of the following criteria will be excluded from enrolment in&#xD;
        this study:&#xD;
&#xD;
          -  Nasal anatomical deformity, nasal airway obstruction; patient who have had recent&#xD;
             oral, nasal or oesophageal surgery or patient presenting with facial and/or cranial&#xD;
             fractures or any other circumstance (e.g. history of oesophageal perforation,&#xD;
             stricture, pouch, resection or rupture) where the placement of a standard nasogastric&#xD;
             feeding tube (NGT) would be deemed unsafe,&#xD;
&#xD;
          -  Cardiac or respiratory condition that might render the insertion (placement) of a&#xD;
             catheter into the throat unsafe,&#xD;
&#xD;
          -  Permanently implanted electrical devices,&#xD;
&#xD;
          -  Are pregnant (pregnancy test) or known lactating women,&#xD;
&#xD;
          -  Have non-neurogenic dysphagia (e.g. Cancer-related),&#xD;
&#xD;
          -  Any prior tracheostomy,&#xD;
&#xD;
          -  Patients who at the time of extubation have any treatment limitation (i.e., palliative&#xD;
             care, life expectancy less than 48 hours, or are moribund), that prevents or would&#xD;
             prevent compliance with study-specific instructions or procedures (as judged by the&#xD;
             investigator),&#xD;
&#xD;
          -  Severe cognitive impairment or other reasons that prevents compliance with&#xD;
             study-specific instructions or procedures (as judged by the investigator),&#xD;
&#xD;
          -  Previous history of dysphagia of any origin,&#xD;
&#xD;
          -  Pre-existing tube feeding of any form (e.g. percutaneous gastric/enteral feeding tube&#xD;
             related to previous injuries indicating previous dysphagia. NGTs are not an exclusion&#xD;
             criterion),&#xD;
&#xD;
          -  Participation in another interventional study (medicinal or device) that could&#xD;
             influence the outcomes of PES,&#xD;
&#xD;
          -  Treatment of dysphagia with other forms of electrical stimulation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joerg Schefold, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Clinic for Intensive Medicine, Inselspital, University of Bern</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Micheal Joannidis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medizinische Universität Innsbruck - Universitätsklinik für Innere Medizin I</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Christopher Rugg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medizinische Universität Innsbruck - Universitätsklinik für Anästhesie und Intensivmedizin</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alois Schiefecker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medizinische Universität Innsbruck - Universitätsklinik für Neurologie</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stefan Kluge, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Hamburg-Eppendorf - Klinik für Intensivmedizin</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Satish Mistry, PhD</last_name>
    <phone>+44 161 820 4525</phone>
    <email>clinical@phagenesis.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Benaka Karanth</last_name>
    <phone>+44 1757 270044</phone>
    <email>bkaranth@namsa.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Medizinische Universität Innsbruck - Medizinische Universität Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020 INNSBRUCK</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alois Schiefecker, MD</last_name>
      <email>alois.schiefecker@tirol-kliniken.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Innsbruck - Universitätsklinik für Anästhesie und Intensivmedizin</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020 INNSBRUCK</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christopher Rugg</last_name>
      <email>christopher.rugg@tirol-kliniken.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Innsbruck - Universitätsklinik für Innere Medizin I</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020 INNSBRUCK</zip>
        <country>Austria</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Micheal Joannidis, MD</last_name>
      <email>michael.joannidis@tirol-kliniken.at</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Helsinki University Hospital Perioperative, Intensive Care and Pain Medicine</name>
      <address>
        <city>Helsinki</city>
        <zip>00029 HUS</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Oulu University Hospital</name>
      <address>
        <city>Oulu</city>
        <zip>90220 OULU</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Hamburg-Eppendorf - Klinik für Intensivmedizin</name>
      <address>
        <city>Hamburg</city>
        <zip>20246 HAMBURG</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>UKE KIM-Studienzentrale</last_name>
      <email>kim-studienzentrale@uke.de</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Clinic for Intensive Medicine, Inselspital</name>
      <address>
        <city>Bern</city>
        <zip>CH-3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joerg C Schefold, MD</last_name>
      <email>Joerg.Schefold@insel.ch</email>
    </contact>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Finland</country>
    <country>Germany</country>
    <country>Switzerland</country>
  </location_countries>
  <link>
    <url>https://pubmed.ncbi.nlm.nih.gov/32176093/</url>
    <description>PhINEST Study - Protocol Manuscript</description>
  </link>
  <reference>
    <citation>Schefold JC, Backlund M, Ala-Kokko T, Zuercher P, Mukherjee R, Mistry S, Mayer SA, Dziewas R, Bakker J, Jakob SM. The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy: Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study. Medicine (Baltimore). 2020 Mar;99(11):e19503. doi: 10.1097/MD.0000000000019503.</citation>
    <PMID>32176093</PMID>
  </reference>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>September 6, 2023</last_update_submitted>
  <last_update_submitted_qc>September 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dysphagia</keyword>
  <keyword>Extubation</keyword>
  <keyword>Intensive Care Unit</keyword>
  <keyword>Pharyngeal Electrical Stimulation</keyword>
  <keyword>Oropharyngeal Dysphagia</keyword>
  <keyword>Mechanical Ventilation</keyword>
  <keyword>Critically ill patients</keyword>
  <keyword>Post-Extubation Dysphagia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deglutition Disorders</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/NCT03840395
org study id: AHE-06
nct id: NCT03840395
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a prospective, multi-site, randomised, sham-controlled, single-blind (outcome
      assessor-blinded) study designed to assess the effects of Pharyngeal Electrical Stimulation
      (PES) (using Phagenyx®) for the treatment of oropharyngeal dysphagia after invasive
      mechanical ventilation (of any duration) by means of naso or oro-tracheal tube in critically
      ill intensive care unit (ICU) patients.
The PhINEST study is designed to assess the effects of Pharyngeal Electrical Stimulation
      (PES) (using Phagenyx®) for treatment of oropharyngeal dysphagia after invasive mechanical
      ventilation (of any duration) by means of naso or oro-tracheal tube in critically ill
      intensive care unit (ICU) patients.

      The main clinical outcomes assessing unsafe swallows and dysphagia severity will be measured
      using the gold standard, i.e. Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and
      bedside swallowing assessments on day 2* after completion of final PES treatment.

      Randomisation will be on a 1:1 basis at each site stratified for neurological vs.
      non-neurological reason for admission (Acute Physiology and Chronic Health Evaluation
      (APACHE) IV diagnostic group). Patients will receive either PES/sham treatment in addition to
      standard supportive ICU care and standard of care treatments for dysphagia. Administration of
      all protocol-specific assessments will be conducted by personnel blinded to treatment
      assignment.

      The study will follow an adaptive population enrichment and sample size re-estimation (SSR)
      design with one interim look. The study will start with a planned sample size of 200 patients
      and a maximum (evaluable) sample size of 360. Interim analysis after completion of
      approximately 140 (evaluable) patients will determine:

      I. futility stopping; OR II. sample size increase for the overall sampled population; OR III.
      Enrichment based on the composite primary endpoint by pre-defined subgroups (neurological vs.
      non-neurological reason for admission according to APACHE IV diagnostic groups). Thus
      enrollment of patients in the non-performing sub-group will be stopped at the interim while a
      sample-size re-estimation based on conditional power will be carried out for the other
      sub-group.

      All interim decisions will be based on conditional power which for the Finkelstein-Schoenfeld
      (FS)-statistic will need to be computed via Monte-Carlo simulations.

      Up to thirty (30) investigational sites across Europe are planned to participate in this
      study which is expected to last 48 months from first patient first visit to last patient last
      visit. Patients will be assessed at the following intervals: screening, baseline, on day 2*
      after completion of final study treatment, 7 ± 1 days after final study treatment and 14 ± 1
      days after final study treatment (or hospital discharge if earlier). 30-day and 90-day
      mortality data will also be collected from the patients medical notes/electronic heath
      records/telephone call (no additional visit required).

      *The day two (FU1) visit is to be conducted on the second day (~24hrs) following final PES
      treatment but may, under certain circumstances, be conducted upon/by the fourth day (~60 hrs)
      following final study treatment in instances where the final study treatment is delivered on
      late Friday and where FEES assessment is only possible early on Monday as no weekend FEES
      service is available at the investigation site.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
measure: Effectiveness of Phagenyx® treatment in reducing severity of unsafe swallows - Penetration-Aspiration Scale (PAS) Scores
time frame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
description: Analysis of a two endpoints composite (FS-statistic) on a hierarchy of clinical priorities:
Endpoint 1 - Swallowing safety based on worst PAS score in up to 4 thin (water) boli for each patient during FEES assessment converted to a trichotomised ordinal response of safe (PAS 1-3), penetration (PAS 4-5), or aspiration (PAS 6-8).
The PAS provides a scoring system for airway closure and clearance during FEES. The PAS is a validated 8-point scale quantifying penetration and aspiration events primarily by the depth to which material passes into the airway and whether or not it is ejected.
measure: Effectiveness of Phagenyx® treatment in reducing the severity of unsafe swallows - Dysphagia Outcome and Severity Score (DOSS) score
time frame: 7±1 days after the final Phagenyx® treatment
description: Analysis of a two endpoints composite (FS-statistic) on a hierarchy of clinical priorities:
Endpoint 2 - DOSS scale score determined by bedside assessment.
The DOSS is a simple, easy-to-use, 7-point scale developed to systematically rate the functional severity of dysphagia based on objective assessment and make recommendations for diet level, independence level, and type of nutrition.
Severe dysphagia
Moderately severe dysphagia
Moderate dysphagia
Mild-moderate dysphagia
Mild dysphagia
Functional limitation and modified independence
Normal in all situations
measure: Effectiveness of Phagenyx® treatment in improving DOSS score.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by the DOSS score.
measure: Effectiveness of Phagenyx® treatment on time from to feeding tube removal.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by time from randomisation to removal of feeding tube.
measure: Effectiveness of Phagenyx® treatment on time to oral intake.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by time to oral intake (if applicable).
measure: Effectiveness of Phagenyx® treatment on total days of enteral feeding.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by total days of enteral feeding.
measure: Effectiveness of Phagenyx® treatment in improving Functional Oral Intake Scale (FOIS) score.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by the FOIS score.
The FOIS provides a scoring system to document the functional level of oral intake of food and liquid in patients with dysphagia. It is a validated 7-point ordinal scale easily completed from information contained in medical charts, dietary journals, and/or patient reports.
Nothing by mouth
Tube dependent with minimal attempts of food or liquid
Tube dependent with consistent intake of liquid or food
Total oral diet of a single consistency
Total oral diet with multiple consistencies but requiring special preparation or compensations
Total oral diet with multiple consistencies without special preparation, but with specific food limitations
Total oral diet with no restriction
measure: Effectiveness of Phagenyx® treatment in improving Dysphagia Severity Rating Scale (DSRS) score.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Changes in nutritional management and severity of dysphagia as measured by the DSRS score.
The DSRS is a simple to use, validated 13-point scale composed of a 3-component score that includes feeding independence, but nutrition level and diet modification is split into the components of liquid feeding and overall diet consistency. The DSRS is the sum of the scores of each of the 3 individual components (range 0-4 for each component) rather than a combination of the three components into an ordinal scale.
Best score = 0 (no dysphagia) Worst score = 12 (NPO)
measure: Effectiveness of Phagenyx® treatment on time from extubation to ICU discharge
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: General health outcome measured by time from extubation to ICU discharge (days).
measure: Effectiveness of Phagenyx® treatment on length of stay in ICU
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: General health outcome measured by length of stay in ICU (days).
measure: Effectiveness of Phagenyx® treatment on length of stay in hospital.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: General health outcome measured by length of stay in hospital (days).
measure: Effectiveness of Phagenyx® treatment on number of patients with re-intubation during hospital stay
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: General health outcome measured by number of patients with re-intubation during hospital stay.
measure: Effectiveness of Phagenyx® treatment on mortality
time frame: Up to 90 days after completion of the final Phagenyx® treatment.
description: General health outcome measured by 30-day and 90-day mortality.
measure: Effectiveness of Phagenyx® treatment in reducing (dysphagia) secretion severity.
time frame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
description: Exploratory analysis of changes in secretion severity (severity of dysphagia) between FEES assessments measured by an Independent FEES Review Committee (IFRC) using the Murray Secretion Severity Rating Scale (SSS).
The SSS is a simple, easy-to-use, 4-point scale that can systematically rate the graduation of accumulated secretions within the pharyngolarynx and trachea during FEES.
0. Normal
Mild
Moderate
Severe
measure: Effectiveness of Phagenyx® treatment in improving swallowing safety and efficiency - PAS scores
time frame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
description: Exploratory analysis of changes in swallowing safety and efficiency (severity of dysphagia) between FEES assessments measured by an IFRC based on worst PAS score for each bolus consistency (semi-solid and solid) for each patient during FEES assessment converted to a dichotomised ordinal response of non-aspirator (PAS 1-5) or aspirator (PAS 6-8).
measure: Effectiveness of Phagenyx® treatment in reducing bolus residue
time frame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
description: Exploratory analysis of changes in bolus residue (severity of dysphagia) between FEES assessments measured by an IFRC using the Yale Pharyngeal Residue Severity Rating Scale (YRS).
The YRS is a reliable, validated, anatomically defined, and image-based five-point ordinal rating scale to determine severity of post-swallow pharyngeal residue location (vallecula and pyriform sinus) and amount (i. none, ii. trace, iii. mild, iv. moderate, and v. severe) during FEES.
measure: Effectiveness of Phagenyx® treatment in reducing global dysphagia severity
time frame: Day 2 (~24 to ~60 hours) after the final Phagenyx® treatment
description: Exploratory analysis of changes in severity of dysphagia between FEES assessments measured by an IFRC using the Global Dysphagia Severity Rating Scale (GDS).
The GDS is a simple, easy-to-use, 4-point scale developed to systematically rate the severity of dysphagia during FEES.
0. No relevant dysphagia
Mild dysphagia: Premature spillage and/or residues, but no penetration/aspiration events.
Moderate dysphagia: Penetration/aspiration events with one consistency.
Severe dysphagia: Penetration/aspiration events with two or more consistencies.
measure: Effectiveness of Phagenyx® treatment on time from extubation to hospital discharge
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Exploratory analysis of general health outcome measured by time from extubation to hospital discharge (days).
measure: Effectiveness of Phagenyx® treatment on days on antimicrobials post-extubation (while in ICU)
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Exploratory analysis of general health outcome measured by days on antimicrobials post-extubation (while in ICU).
measure: Effectiveness of Phagenyx® treatment on hospital discharge destination
time frame: Up to 90 days after the final Phagenyx® treatment
description: Exploratory analysis of general health outcome measured by hospital discharge destination (home, home+care, nursing home, other hospital, rehabilitation centre).
measure: Effectiveness of Phagenyx® treatment on ICU readmission rate during hospital stay
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Exploratory analysis of general health outcome measured by ICU readmission rate during hospital stay.
measure: Effectiveness of Phagenyx® treatment on tracheostomies per subgroup
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Exploratory analysis of general health outcome measured by number of and reason for tracheostomies per subgroup after PES-treatment during hospital stay.
measure: Effectiveness of Phagenyx® treatment on chest X-rays for suspected pneumonia.
time frame: Up to 14 ± 1 days after the final Phagenyx® treatment (or hospital discharge if earlier).
description: Exploratory analysis of general health outcome measured by total number of chest X-rays during hospital stay after ICU discharge for suspected pneumonia.
arm group label: Active PES
arm group type: Active Comparator
description: Patients randomized to receive active Pharyngeal Electrical Stimulation (PES) via a Phagenyx Catheter.
arm group label: Sham PES
arm group type: Sham Comparator
description: Patients randomized to sham will not receive any Pharyngeal Electrical Stimulation (PES) but will still have the Phagenyx Catheter inserted.
intervention type: Device
intervention name: Pharyngeal Electrical Stimulation (PES)
description: The Phagenyx® system is a two-part neurostimulation system. It is composed of a durable component called the Base Station and the single-use sterile disposable Catheter. The Base Station acts as the user interface and provides the means to generate, optimize and monitor the delivery of electrical stimulation to the oropharynx. The Phagenyx® devices are CE labelled (2012) and will be used in accordance with their intended use label.
arm group label: Active PES
arm group label: Sham PES
other name: Phagenyx
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Joerg Schefold, MD
role: Principal Investigator
affiliation: University Clinic for Intensive Medicine, Inselspital, University of Bern
last name: Micheal Joannidis, MD
role: Principal Investigator
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Innere Medizin I
last name: Christopher Rugg, MD
role: Principal Investigator
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Anästhesie und Intensivmedizin
last name: Alois Schiefecker, MD
role: Principal Investigator
affiliation: Medizinische Universität Innsbruck - Universitätsklinik für Neurologie
last name: Stefan Kluge, MD
role: Principal Investigator
affiliation: Universitätsklinikum Hamburg-Eppendorf - Klinik für Intensivmedizin
last name: Satish Mistry, PhD
phone: +44 161 820 4525
email: clinical@phagenesis.com
last name: Benaka Karanth
phone: +44 1757 270044
email: bkaranth@namsa.com
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Austria
country: Finland
country: Germany
country: Switzerland
url: https://pubmed.ncbi.nlm.nih.gov/32176093/
description: PhINEST Study - Protocol Manuscript
citation: Schefold JC, Backlund M, Ala-Kokko T, Zuercher P, Mukherjee R, Mistry S, Mayer SA, Dziewas R, Bakker J, Jakob SM. The PhINEST study - Pharyngeal ICU Novel Electrical Stimulation Therapy: Study protocol of a prospective, multi-site, randomized, sham-controlled, single-blind (outcome assessor-blinded) study. Medicine (Baltimore). 2020 Mar;99(11):e19503. doi: 10.1097/MD.0000000000019503.
PMID: 32176093
responsible party type: Sponsor
mesh term: Deglutition Disorders
sharing ipd: No