<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/NCT03803722</url>
  </required_header>
  <id_info>
    <org_study_id>048/SI</org_study_id>
    <nct_id>NCT03803722</nct_id>
  </id_info>
  <brief_title>To Demonstrate the Non-inferiority of Eyestil Protection® Compared to Vismed® in Terms of Clinical Performance</brief_title>
  <official_title>A Prospective Multicenter, Comparative, Randomized, Single-blind, Non-inferiority Study of Eyestil Protection® Unidose Versus Vismed® Unidose in Patients With Moderate to Severe Dry Eye Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SIFI SpA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SIFI SpA</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 is a national, prospective, multicenter, comparative, randomized, single-blinded&#xD;
      non-inferiority study performed in two parallel groups.&#xD;
&#xD;
      3 months (plus a run in period of 15 days prior inclusion) Patients with moderate to severe&#xD;
      dry eye syndrome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Public hospitals and private practices specialized in ophthalmology Approximately 10 sites&#xD;
      France Approximately 80 patients globally: 40 per arm with a 1:1 ratio including an expected&#xD;
      dropout rate of 15%.&#xD;
&#xD;
      Dry eye has been defined as a multifactorial disease of the ocular surface characterized by a&#xD;
      loss of homeostasis of the tear film and accompanied by ocular symptoms, in which the tear&#xD;
      film instability and hyperosmolarity, ocular surface inflammation and damage, and&#xD;
      neurosensory abnormalities play etiological roles.&#xD;
&#xD;
      However, prevalence estimates for dry eye vary dramatically from 5% to 50% due to the various&#xD;
      operational definitions of dry eye used and the characteristics of the population studied.&#xD;
&#xD;
      The available evidence suggests also that dry eye has a negative impact on overall quality of&#xD;
      life. It causes pain and irritation and affects ocular and general health and well-being, the&#xD;
      perception of visual function and visual performance. Reduced quality of life in everyday&#xD;
      activities and leisure pursuits is reported by 60% of patients, while 38% of patients&#xD;
      complain of reduced efficiency at work.&#xD;
&#xD;
      Therefore, the economic burden and impact of dry eye on vision and quality of life, work&#xD;
      productivity, psychological and physical impact of pain are considerable. As a consequence,&#xD;
      dry eye represents a public health burden. However, only a handful of therapies are available&#xD;
      for dry eye patient and are used according to the disease severity.&#xD;
&#xD;
      In such context, SIFI SpA. has developed Eyestil Protection® (or SF-104 XNT Single dose). It&#xD;
      is a sterile preservative-free device (eye drops) for ophthalmic use containing 0.2% xanthan&#xD;
      gum, presented in 0.3 ml unidose containers. The main action of Eyestil Protection is to&#xD;
      lubricate and moisturize the ocular surface as well as to protect it from oxidative stress&#xD;
      thanks to the anti-oxidative properties of the xanthan gum (as demonstrated by in-vitro&#xD;
      studies (Amico, Tornetta et al. 2015). It is indicated in all cases of dry-eye related ocular&#xD;
      discomfort and to relief ocular discomfort due to the use of contact lenses.&#xD;
&#xD;
      Eyestil Protection® unidose is CE marked but is not available yet in all European countries,&#xD;
      notably in France.&#xD;
&#xD;
      Confronted to a European regulatory change on medical devices - from a Directive (Directive&#xD;
      1993/42/EEC) to a Regulation (MDR 2017/745) that now requires clinical evidence of device&#xD;
      performance and safety; SIFI SpA decided to implement the present clinical comparative&#xD;
      performance study. The choice of Vismed® (unidose) as the comparator has been done since it&#xD;
      is the current French standard of care treatment for patients with moderate to severe dry&#xD;
      eyes.&#xD;
&#xD;
      Primary objective&#xD;
&#xD;
      • To demonstrate the non-inferiority of Eyestil Protection® compared to Vismed® in terms of&#xD;
      clinical performance as detected by a reduction of keratitis lesions objectified by staining&#xD;
      tests after 1 month of treatment, in patients with moderate to severe dry eye syndrome with&#xD;
      keratoconjunctivitis.&#xD;
&#xD;
      Secondary objectives Clinical performance&#xD;
&#xD;
        -  To evaluate the tear film stability per group as objectified by the tear break up time&#xD;
           (TBUT) test at month 1 and 3;&#xD;
&#xD;
        -  To evaluate the long term clinical performance of Eyestil Protection® compared to&#xD;
           Vismed® as detected by a reduction of keratitis lesions objectified by staining tests&#xD;
           after 3 months of treatment;&#xD;
&#xD;
        -  To evaluate the tear production per group as objectified by the Schirmer test at month&#xD;
           3.&#xD;
&#xD;
      Patient reported outcomes&#xD;
&#xD;
        -  To compare patients reported outcomes (PRO) measures per group at month 1 and 3,&#xD;
           including:&#xD;
&#xD;
             -  Patient's reported symptoms and&#xD;
&#xD;
             -  Patient's quality of life (QoL). Investigator overall satisfaction&#xD;
&#xD;
        -  To assess investigator's overall satisfaction of the treatment's clinical performance at&#xD;
           month 1 and 3.&#xD;
&#xD;
      Safety • To describe the safety profile of Eyestil Protection® compared to Vismed® after 3&#xD;
      months of treatment.&#xD;
&#xD;
      Exploratory objectives&#xD;
&#xD;
      • To compare patient's QoL subscale scores per group at each time point.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow enrolment process and COVID situation worsened the situation. SIFI has developed a new&#xD;
    product with probably a better performance. SIFI changed its marketing strategy and decided&#xD;
    that Eyestil® Protection will be not marketed anymore&#xD;
  </why_stopped>
  <start_date type="Actual">July 8, 2019</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</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>
    <intervention_model_description>Approximately 80 patients globally: 40 per arm with a 1:1 ratio including an expected dropout rate of 15%. Single masked. Medical Device</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Single Blind: investigator masked</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Primary endpoint/clinical performance by Oxford scale</measure>
    <time_frame>between Day 1 and Day 35 ±4.</time_frame>
    <description>Clinical performance of the medical device under investigation: the between-group comparison of the average variation of the global fluorescein corneal and lissamine green conjunctival staining using the Oxford scale (0 to 15). This refers to the average variation between both time points of the Global Ocular Staining Score of the study eye (GOSS).&#xD;
0-5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/clinical performance by TBUT test</measure>
    <time_frame>between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7</time_frame>
    <description>The between-group comparisons of the average variation of the time obtained at the tear break up time test (TBUT). This full procedure will be performed 3 times per eye and per time point. Each obtained time will be recorded by the investigator in the eCRF. At screening and at baseline visits, the sum of these 3 times for at least one eye to be eligible must be ≤ 30 seconds.&#xD;
Conventionally TBUT's measures shorter than 10 seconds can be referred to tear film instability and measures shorter than 5 seconds, usually, are undoubtable sign of dry eye. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement) and a negative number change from baseline indicates a decrease in TBUT (worsening).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/patient reported outcome by DEQS questionnaire</measure>
    <time_frame>between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7</time_frame>
    <description>The between-group comparisons of the average variation of Dry Eye-Related Quality-of-Life (DEQS) general score. It is a validated 15-item scale divided into 2 subscales related to dry eye symptoms and its influence on daily life:&#xD;
The frequency is scored on a 5-point Likert scale ranging from 0 (no symptom) to 4 (highest frequency).&#xD;
• The degree is scored on a 4-point Likert scale ranging from 1 to 4, a larger number indicates a greater burden.&#xD;
The summary score ranges from 0 to 100, higher score indicates higher disability. .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/safety</measure>
    <time_frame>between Day 1 and Day 84 ±7</time_frame>
    <description>The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/clinical performance by Oxford scale</measure>
    <time_frame>between Day 1 and Day 84 ±7</time_frame>
    <description>The between-group comparison of the average variation of the global fluorescein corneal and lissamine green conjunctival staining using the Oxford scale (0-15).This refers to the average variation between both time points of the of the Global Ocular Staining Score of the study eye (GOSS) and the comparison between both treatment groups. -5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/clinical performance by Schirmer test</measure>
    <time_frame>between [Day 1 and Day 84 ±7]</time_frame>
    <description>The between-group comparisons of the average variation of the paper length obtained at the Schirmer Test. The Schirmer test without anesthesia will be here performed to measure the rate of secretion of tears produced by the study eye over 5 minutes.The cut-off value for a severe dry eye in the first one is 6 mm. But the cut-off that will here use will be 9 mm with the following interpretation:&#xD;
Normal = ≥ 10 millimeters (mm) of tears,&#xD;
Dry Eye = ≤ 9 mm of tears A positive number change from baseline indicates an increase in tears (improvement) and a negative number change from baseline indicates a decrease in tears (worsening).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary endpoint/patient reported outcome by OSDI score</measure>
    <time_frame>between [Day 1 and Day 35 ±4] and [Day 1 and Day 84 ±7]</time_frame>
    <description>The between-group comparisons of the average variation of Ocular Symptoms Disease Index (OSDI) score. The patient's dry eye symptoms will be assessed with the Ocular Surface Disease Index (OSDI). It is a validated 12-questions scale for patients that covers a broad spectrum of ocular surface symptoms, the severity of such symptoms for patients and how these symptoms affect/impact visual function over a 1-week recall period. Its scores range from 0 to 100, with higher scores indicating greater severity of disease.Positive result is considered when the OSDI score is ≥ 18.To be consistent with the IMD indication, patient with moderate to severe dry eye thus with an OSDI ≥ 18 will be selected. If the patient's OSDI score will be strictly below 18 at the screening or baseline visit, s/he will be considered as a screening failure.&#xD;
Each item response will be collected in the study database since given separately to patients.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Investigator's overall treatment satisfaction (PRO)</measure>
    <time_frame>at [Day 35±4 and Day 84 ±7].</time_frame>
    <description>The between group comparison using on a four-point scale assessing investigator's overall satisfaction on the treatment's clinical performance&#xD;
• The between group comparison using on a four-point scale assessing investigator's overall satisfaction on the treatment's clinical performance at [Day 35±4 and Day 84 ±7].&#xD;
Overall investigator' satisfaction of the product's clinical performance will be assessed at the end of the patient follow-up period on a four-point scale from 0: very satisfactory, 1: satisfactory; 2: somewhat unsatisfactory; 3: unsatisfactory Safety • The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated.&#xD;
Exploratory endpoints&#xD;
• PROs: the between-group comparisons of the average variation of the DEQS subscale scores between [Day 1 and Day 35 ±4] and [Day 1 and Day 84 ±7].</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Dry Eye Syndrome</condition>
  <arm_group>
    <arm_group_label>Arm A Eyestil Protection®</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>No inferiority of Eyestil Protection® unidose versus Vismed® unidose The intervention consists of Eyestil Protection® : sterile preservative free, medical device, class IIa and CE marked. It contains 0.2% xanthan gum, presented in 0.3 ml unidose containers. It is not available yet on the French Market.&#xD;
dosage: 6 drops a day for three months period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B Vismed®</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Vismed®: sterile preservative free, medical device class IIb and CE marked. It contains 0.18% sodium hyaluronate, presented in 0.3 ml unidose containers. It is already on the French market.&#xD;
dosage: 6 drops a day for three months period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Eyestil Protection® unidose</intervention_name>
    <description>to demonstrate the non-inferiority of Eyestil Protection® in terms of performance and safety, when compared to Vismed® in treatment of dry eye disease.</description>
    <arm_group_label>Arm A Eyestil Protection®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients, male or female, of at least 18 years of age at the screening visit&#xD;
&#xD;
          -  Patients understanding the study, willing to follow the instructions and providing&#xD;
             their written Informed Consent Form to participate&#xD;
&#xD;
          -  Patients with moderate up severe dry eye with keratoconjunctivitis sicca diagnosed at&#xD;
             least 4 weeks before the screening visit&#xD;
&#xD;
          -  Patients using artificial tears at least once a day for at least 4 weeks before the&#xD;
             screening visit&#xD;
&#xD;
          -  Patients with corneal/conjunctival lesions consistent with a diagnosis of&#xD;
             keratoconjunctivitis measured by tests of staining: i.e. the overall score of the&#xD;
             corneal staining test must be ≥ 3 and ≤ 9 on the 15-point Oxford scale&#xD;
&#xD;
          -  And at least one of the following element: Tear volume decreased: must be either&#xD;
             present a Schirmer test ≥ 3 mm and ≤ 9 mm / 5 minutes or the sum of 3 consecutive&#xD;
             measurements of the tear film break-up time (TBUT) ≤ 30s for at least one eye;&#xD;
&#xD;
          -  OSDI score ≥18&#xD;
&#xD;
          -  Covered by healthcare insurance.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with medical history of herpetic keratitis, peripheral ulcerative keratitis,&#xD;
             sclerites, diabetic retinopathy&#xD;
&#xD;
          -  Any systemic disease that is not well controlled for at least 2 months (e.g. lupus,&#xD;
             rheumatoid arthritis, thyroiditis…) according to clinical judgment&#xD;
&#xD;
          -  Patients using any topical therapies such as non-steroidal anti-inflammatory drugs,&#xD;
             cortisone, cyclosporine, vasoconstrictor&#xD;
&#xD;
          -  Patients with at least one of the following concomitant ocular inflammatory disease:&#xD;
             Stevens Johnson Disease, Atopic Keratoconjunctivitis; Scarlet Eye Pemphigoid&#xD;
&#xD;
          -  Patients with anomalies of the eyelid, sucking, infectious conjunctivitis, pterygia,&#xD;
             and/or a glaucoma treated with eyedrops&#xD;
&#xD;
          -  Presence of graft versus host disease (GVHD)&#xD;
&#xD;
          -  Patients who have undergone surgery in the eye, within three months before the study&#xD;
             enrolment&#xD;
&#xD;
          -  Patients who have undergone corneal transplantation or refractive surgery or plan to&#xD;
             undergo any eye surgery in the next four months&#xD;
&#xD;
          -  Patients with known or suspected eye allergy&#xD;
&#xD;
          -  Patients with a condition or history that, in the opinion of the investigator, may&#xD;
             interfere significantly with the subject's participation in the study&#xD;
&#xD;
          -  Female pregnant, planning a pregnancy during the study period and nursing an infant&#xD;
&#xD;
          -  Patients who are participating or have participated in other clinical trial with&#xD;
             investigational drug or device within 30 days prior to screening&#xD;
&#xD;
          -  Patients unable to be compliant with the study procedures and requirements, according&#xD;
             to the opinion of the investigator&#xD;
&#xD;
          -  Patient deprived of liberty by a judicial or administrative decision, or who is under&#xD;
             a measure of legal protection (e.g. guardianship or curatorship)&#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>Marc Labetoulle, MD; Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU KREMLIN-BICETRE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU d'Amiens</name>
      <address>
        <city>Amiens</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Rétine Anjou</name>
      <address>
        <city>Angers</city>
        <zip>49000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cabinet d'ophtalmologie Fosh</name>
      <address>
        <city>Bordeaux</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Vincent de Paul</name>
      <address>
        <city>Lille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Edouard Herriot</name>
      <address>
        <city>Lyon</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Joseph</name>
      <address>
        <city>Marseille</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Kremlin-Bicetre</name>
      <address>
        <city>Paris</city>
        <zip>94270</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APHP - Hôpital Cochin</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Universitaire de Rennes</name>
      <address>
        <city>Rennes</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet</name>
      <address>
        <city>Zaragoza</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>May 6, 2022</last_update_submitted>
  <last_update_submitted_qc>May 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2022</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>Dry Eye Syndromes</mesh_term>
    <mesh_term>Keratoconjunctivitis Sicca</mesh_term>
    <mesh_term>Syndrome</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/NCT03803722
org study id: 048/SI
nct id: NCT03803722
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a national, prospective, multicenter, comparative, randomized, single-blinded
      non-inferiority study performed in two parallel groups.

      3 months (plus a run in period of 15 days prior inclusion) Patients with moderate to severe
      dry eye syndrome.
Public hospitals and private practices specialized in ophthalmology Approximately 10 sites
      France Approximately 80 patients globally: 40 per arm with a 1:1 ratio including an expected
      dropout rate of 15%.

      Dry eye has been defined as a multifactorial disease of the ocular surface characterized by a
      loss of homeostasis of the tear film and accompanied by ocular symptoms, in which the tear
      film instability and hyperosmolarity, ocular surface inflammation and damage, and
      neurosensory abnormalities play etiological roles.

      However, prevalence estimates for dry eye vary dramatically from 5% to 50% due to the various
      operational definitions of dry eye used and the characteristics of the population studied.

      The available evidence suggests also that dry eye has a negative impact on overall quality of
      life. It causes pain and irritation and affects ocular and general health and well-being, the
      perception of visual function and visual performance. Reduced quality of life in everyday
      activities and leisure pursuits is reported by 60% of patients, while 38% of patients
      complain of reduced efficiency at work.

      Therefore, the economic burden and impact of dry eye on vision and quality of life, work
      productivity, psychological and physical impact of pain are considerable. As a consequence,
      dry eye represents a public health burden. However, only a handful of therapies are available
      for dry eye patient and are used according to the disease severity.

      In such context, SIFI SpA. has developed Eyestil Protection® (or SF-104 XNT Single dose). It
      is a sterile preservative-free device (eye drops) for ophthalmic use containing 0.2% xanthan
      gum, presented in 0.3 ml unidose containers. The main action of Eyestil Protection is to
      lubricate and moisturize the ocular surface as well as to protect it from oxidative stress
      thanks to the anti-oxidative properties of the xanthan gum (as demonstrated by in-vitro
      studies (Amico, Tornetta et al. 2015). It is indicated in all cases of dry-eye related ocular
      discomfort and to relief ocular discomfort due to the use of contact lenses.

      Eyestil Protection® unidose is CE marked but is not available yet in all European countries,
      notably in France.

      Confronted to a European regulatory change on medical devices - from a Directive (Directive
      1993/42/EEC) to a Regulation (MDR 2017/745) that now requires clinical evidence of device
      performance and safety; SIFI SpA decided to implement the present clinical comparative
      performance study. The choice of Vismed® (unidose) as the comparator has been done since it
      is the current French standard of care treatment for patients with moderate to severe dry
      eyes.

      Primary objective

      • To demonstrate the non-inferiority of Eyestil Protection® compared to Vismed® in terms of
      clinical performance as detected by a reduction of keratitis lesions objectified by staining
      tests after 1 month of treatment, in patients with moderate to severe dry eye syndrome with
      keratoconjunctivitis.

      Secondary objectives Clinical performance

        -  To evaluate the tear film stability per group as objectified by the tear break up time
           (TBUT) test at month 1 and 3;

        -  To evaluate the long term clinical performance of Eyestil Protection® compared to
           Vismed® as detected by a reduction of keratitis lesions objectified by staining tests
           after 3 months of treatment;

        -  To evaluate the tear production per group as objectified by the Schirmer test at month
           3.

      Patient reported outcomes

        -  To compare patients reported outcomes (PRO) measures per group at month 1 and 3,
           including:

             -  Patient's reported symptoms and

             -  Patient's quality of life (QoL). Investigator overall satisfaction

        -  To assess investigator's overall satisfaction of the treatment's clinical performance at
           month 1 and 3.

      Safety • To describe the safety profile of Eyestil Protection® compared to Vismed® after 3
      months of treatment.

      Exploratory objectives

      • To compare patient's QoL subscale scores per group at each time point.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Approximately 80 patients globally: 40 per arm with a 1:1 ratio including an expected dropout rate of 15%. Single masked. Medical Device
primary purpose: Other
masking: Single (Investigator)
masking description: Single Blind: investigator masked
measure: Primary endpoint/clinical performance by Oxford scale
time frame: between Day 1 and Day 35 ±4.
description: Clinical performance of the medical device under investigation: the between-group comparison of the average variation of the global fluorescein corneal and lissamine green conjunctival staining using the Oxford scale (0 to 15). This refers to the average variation between both time points of the Global Ocular Staining Score of the study eye (GOSS).
0-5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15
measure: Secondary endpoint/clinical performance by TBUT test
time frame: between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7
description: The between-group comparisons of the average variation of the time obtained at the tear break up time test (TBUT). This full procedure will be performed 3 times per eye and per time point. Each obtained time will be recorded by the investigator in the eCRF. At screening and at baseline visits, the sum of these 3 times for at least one eye to be eligible must be ≤ 30 seconds.
Conventionally TBUT's measures shorter than 10 seconds can be referred to tear film instability and measures shorter than 5 seconds, usually, are undoubtable sign of dry eye. The longer it takes, the more stable the tear film. A short TBUT is a sign of poor tear film. A positive number change from baseline indicates an increase in TBUT (improvement) and a negative number change from baseline indicates a decrease in TBUT (worsening).
measure: Secondary endpoint/patient reported outcome by DEQS questionnaire
time frame: between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7
description: The between-group comparisons of the average variation of Dry Eye-Related Quality-of-Life (DEQS) general score. It is a validated 15-item scale divided into 2 subscales related to dry eye symptoms and its influence on daily life:
The frequency is scored on a 5-point Likert scale ranging from 0 (no symptom) to 4 (highest frequency).
• The degree is scored on a 4-point Likert scale ranging from 1 to 4, a larger number indicates a greater burden.
The summary score ranges from 0 to 100, higher score indicates higher disability. .
measure: Secondary endpoint/safety
time frame: between Day 1 and Day 84 ±7
description: The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated
measure: Secondary endpoint/clinical performance by Oxford scale
time frame: between Day 1 and Day 84 ±7
description: The between-group comparison of the average variation of the global fluorescein corneal and lissamine green conjunctival staining using the Oxford scale (0-15).This refers to the average variation between both time points of the of the Global Ocular Staining Score of the study eye (GOSS) and the comparison between both treatment groups. -5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15
measure: Secondary endpoint/clinical performance by Schirmer test
time frame: between [Day 1 and Day 84 ±7]
description: The between-group comparisons of the average variation of the paper length obtained at the Schirmer Test. The Schirmer test without anesthesia will be here performed to measure the rate of secretion of tears produced by the study eye over 5 minutes.The cut-off value for a severe dry eye in the first one is 6 mm. But the cut-off that will here use will be 9 mm with the following interpretation:
Normal = ≥ 10 millimeters (mm) of tears,
Dry Eye = ≤ 9 mm of tears A positive number change from baseline indicates an increase in tears (improvement) and a negative number change from baseline indicates a decrease in tears (worsening).
measure: Secondary endpoint/patient reported outcome by OSDI score
time frame: between [Day 1 and Day 35 ±4] and [Day 1 and Day 84 ±7]
description: The between-group comparisons of the average variation of Ocular Symptoms Disease Index (OSDI) score. The patient's dry eye symptoms will be assessed with the Ocular Surface Disease Index (OSDI). It is a validated 12-questions scale for patients that covers a broad spectrum of ocular surface symptoms, the severity of such symptoms for patients and how these symptoms affect/impact visual function over a 1-week recall period. Its scores range from 0 to 100, with higher scores indicating greater severity of disease.Positive result is considered when the OSDI score is ≥ 18.To be consistent with the IMD indication, patient with moderate to severe dry eye thus with an OSDI ≥ 18 will be selected. If the patient's OSDI score will be strictly below 18 at the screening or baseline visit, s/he will be considered as a screening failure.
Each item response will be collected in the study database since given separately to patients.
measure: Investigator's overall treatment satisfaction (PRO)
time frame: at [Day 35±4 and Day 84 ±7].
description: The between group comparison using on a four-point scale assessing investigator's overall satisfaction on the treatment's clinical performance
• The between group comparison using on a four-point scale assessing investigator's overall satisfaction on the treatment's clinical performance at [Day 35±4 and Day 84 ±7].
Overall investigator' satisfaction of the product's clinical performance will be assessed at the end of the patient follow-up period on a four-point scale from 0: very satisfactory, 1: satisfactory; 2: somewhat unsatisfactory; 3: unsatisfactory Safety • The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated.
Exploratory endpoints
• PROs: the between-group comparisons of the average variation of the DEQS subscale scores between [Day 1 and Day 35 ±4] and [Day 1 and Day 84 ±7].
arm group label: Arm A Eyestil Protection®
arm group type: Experimental
description: No inferiority of Eyestil Protection® unidose versus Vismed® unidose The intervention consists of Eyestil Protection® : sterile preservative free, medical device, class IIa and CE marked. It contains 0.2% xanthan gum, presented in 0.3 ml unidose containers. It is not available yet on the French Market.
dosage: 6 drops a day for three months period.
arm group label: Arm B Vismed®
arm group type: No Intervention
description: Vismed®: sterile preservative free, medical device class IIb and CE marked. It contains 0.18% sodium hyaluronate, presented in 0.3 ml unidose containers. It is already on the French market.
dosage: 6 drops a day for three months period.
intervention type: Device
intervention name: Eyestil Protection® unidose
description: to demonstrate the non-inferiority of Eyestil Protection® in terms of performance and safety, when compared to Vismed® in treatment of dry eye disease.
arm group label: Arm A Eyestil Protection®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc Labetoulle, MD; Pr
role: Principal Investigator
affiliation: CHU KREMLIN-BICETRE
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country: France
country: Spain
responsible party type: Sponsor
mesh term: Dry Eye Syndromes
mesh term: Keratoconjunctivitis Sicca
mesh term: Syndrome