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A Non-inferiority Study of Eyestil® Plus Multidose Versus Vismed Multi® (047/SI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03803748
Recruitment Status : Recruiting
First Posted : January 15, 2019
Last Update Posted : May 27, 2020
Sponsor:
Information provided by (Responsible Party):
SIFI SpA

Brief Summary:

SIFI SpA had developed Eyestil Plus®. It is sterile eyedrops without preservatives with a physiological pH containing sodium hyaluronate. Its intended purpose is to moisturize, lubricate and protect the ocular surface and gives temporary relief to burning, irritation and dry eye-related discomfort, and other complaints induced, for example, by: prolonged use of either soft, semi rigid or rigid contact lenses; exposure to environmental factors (air conditioning, exposure to solar radiation, wind, smoke, pollution, severe climatic conditions, dust); ocular fatigue caused by studying, working, driving or prolonged exposure to electronic devices.

Eyestil Plus® is CE marked but not available yet in all European countries. Considering the 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 Multi® as the comparator has been done since it is the current French standard of care treatment for patients with moderate to severe dry eyes.


Condition or disease Intervention/treatment Phase
Dry Eye Syndromes Device: Eyestil Plus® Not Applicable

Detailed Description:
The aim of the study is to demonstrate the non-inferiority of Eyestil Plus® compared to Vismed Multi® 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. Secondly, the study is aimed at evaluating the safety profile of the product and the patients' quality of life.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a national, prospective, multicenter, comparative, randomized, double-blinded non-inferiority study performed in two parallel groups.
Masking: Double (Participant, Investigator)
Masking Description: Double blind
Primary Purpose: Other
Official Title: A Prospective Multicenter, Comparative, Randomized, Double-blind, Non-inferiority Study of Eyestil® Plus Multidose Versus Vismed Multi® in Patients With Moderate to Severe Dry Eye Syndrome
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020

Arm Intervention/treatment
Experimental: Eyestil Plus®

It's a clinical comparative performance study. Eyestil Plus® eyedrops multidose to be not inferior to Vismed multidose eye drops. Eyestil Plus is an ophthalmic aqueous formulation, multidose sterile preservative free, medical device, class IIB and CE marked. It contains 0.4% sodium hyaluronate. It is not available yet in the French Market.

The dosage per medical device will be 6 drops a day per dry eye during the three months study period,

Device: Eyestil Plus®
• To demonstrate the non-inferiority of Eyestil Plus® compared to Vismed Multi® 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

No Intervention: Vismed

Vismed Multi® is also a sterile multidose preservative free, medical device class IIb and CE marked. It contains 0.18% sodium hyaluronate.

The dosage per medical device will be 6 drops a day per dry eye during the three months study period.

The choice of Vismed Multi® 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 Outcome Measures :
  1. Primary endpoint/clinical performance by Oxford scale [ Time Frame: between Day 1 and Day 35 ±4 ]
    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 timepoints of the Global Ocular Staining Score of the study eye (GOSS) and the comparison between both treatment groups. 0-5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15


Secondary Outcome Measures :
  1. secondary endpoint/clinical performance by TBUT test [ Time Frame: between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7 ]

    The between-group comparisons of the average variation of the time obtained at the TBUT test. This full procedure will be performed 3 times per eye and per time point. 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).


  2. secondary endpoint/clinical performance by Oxford scale [ Time Frame: between Day 1 and Day 84 ±7 days ]
    The between-group comparison of the average variation of the global fluorescein corneal and lissamine green conjunctival staining using the Oxford scale. This refers to the average variation between both time points of the Global Ocular Staining Score of the study eye (GOSS) and the comparison between both treatment groups. 0-5 cornea; 0-5 temporal conjuctiva; 0-5 nasal conjunctiva. Max total score: 15

  3. secondary endpoint/clinical performance by Schirmer Test [ Time Frame: test between Day 1 and Day 84 ±7 ]

    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).

  4. secondary endpoint/patient symptoms by Ocular Symptoms Disease Index (OSDI) score [ Time Frame: Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7 ]
    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.

  5. secondary endpoint/patient symptoms by Dry Eye-Related Quality -of-Life(DEQS) questionnaire [ Time Frame: Day 1 and Day 35 ±4 and [Day 1 and Day 84 ±7 ]

    The between-group comparisons of the average variation of Dry Eye-Related Quality-of-Life (DEQS) questionnaire. 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


  6. secondary endpoint/safety [ Time Frame: Day 1 and Day 84 ±7 ]
    The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated.

  7. secondary endpoint/Investigator overall treatment satisfaction using by a four-point scale [ Time Frame: Day 35±4 and Day 84 ±7 ]
    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. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, male or female, of at least 18 years of age at the screening visit
  • Patients understanding the study, willing to follow the instructions and providing their written Informed Consent Form to participate
  • Patients with moderate up severe dry eye with keratoconjunctivitis sicca diagnosed at least 4 weeks before the screening visit
  • Patients using artificial tears at least once a day for at least 4 weeks months before the screening visit*
  • Patients with corneal/conjunctival lesions consistent with a diagnosis of keratoconjunctivitis measured by tests of staining: i.e. the overall score of the corneal staining test must be ≥ 3 and ≤ 9 on the 15-point Oxford scale
  • And at least one of the following element:

Tear volume decreased: must be either present a Schirmer test ≥ 3 mm and ≤ 9 mm / 5 minutes or the sum of 3 consecutive measurements of the tear film break-up time (TBUT) ≤ 30s for at least one eye An OSDI score ≥18

- Covered by healthcare insurance.

Exclusion Criteria:

  • Patients with medical history of herpetic keratitis, peripheral ulcerative keratitis, sclerites, diabetic retinopathy
  • Any systemic disease that is not well controlled for at least 2 months (e.g. lupus, rheumatoid arthritis, thyroiditis…) according to clinical judgment
  • Patients using any topical therapies such as non-steroidal anti-inflammatory drugs, cortisone, cyclosporine, vasoconstrictor
  • Patients with at least one of the following concomitant ocular inflammatory disease: Stevens Johnson Disease, Atopic Keratoconjunctivitis; Scarlet Eye Pemphigoid
  • Patients with anomalies of the eyelid, sucking, infectious conjunctivitis, pterygia, and/or a glaucoma treated with eyedrops
  • Presence of graft versus host disease (GVHD)
  • Patients who have undergone surgery in the eye, within three months before the study enrolment
  • Patients who have undergone corneal transplantation or refractive surgery or plan to undergo any eye surgery in the next four months
  • Patients with known or suspected eye allergy
  • Patients with a condition or history that, in the opinion of the investigator, may interfere significantly with the subject's participation in the study
  • Female pregnant, planning a pregnancy during the study period and nursing an infant
  • Patients who are participating or have participated in other clinical trial with investigational drug or device within 30 days prior to screening
  • Patients unable to be compliant with the study procedures and requirements, according to the opinion of the investigator
  • Patient deprived of liberty by a judicial or administrative decision, or who is under a measure of legal protection (e.g. guardianship or curatorship).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03803748


Contacts
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Contact: Pierre Jean PISELLA, MD, Pr +33 247478766 pisella@med.univ-tours.fr

Locations
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France
CHU de Bordeaux - Hôpital Pellegrin Recruiting
Bordeaux, France
Contact: David Touboul, MD       david.touboul@chu-bordeaux.fr   
Principal Investigator: David Touboul, MD         
Chu Morvan Recruiting
Brest, France
Contact: Béatrice Cochener, MD       beatrice.cochener@ophtalmologie-chu29.fr   
Principal Investigator: Béatrice Cochener, MD         
CHU François Mitterand Recruiting
Dijon, France
Contact: Catherine Creuzot-Garcher, MD       catherine.creuzot-garcher@chu-dijon.fr   
Principal Investigator: Catherine Creuzot-Garcher, MD         
Hôpital de la Croix Rousse Recruiting
Lyon, France
Contact: Laurent Kodjikian, MD       laurent.kodjikian@chu-lyon.fr   
Principal Investigator: Laurent Kodjikian, MD         
Centre Monticelli Recruiting
Marseille, France
Contact: Stéphane Fauquier, MD       contact@dr-fauquier.fr   
Principal Investigator: Stéphane Fauquier, MD         
Hopital La Timone Adultes Recruiting
Marseille, France
Contact: Gaelle Ho Wang Yin, MD       GAELLE.HO-WANG-YIN@ap-hm.fr   
Principal Investigator: Gaelle Ho Wang Yin, MD         
CHU de Nice - Hôpital Pasteur Recruiting
Nice, France
Contact: Stéphanie Baillif, MD       baillif-gostoli.s@chu-nice.fr   
Principal Investigator: Stéphanie Baillif, MD         
CHU Saint Etienne/Hôpital Nord Recruiting
Saint-Étienne, France
Contact: Philippe Gain, MD       philippe.gain@univ-st-etienne.fr   
Principal Investigator: Philippe Gain, MD         
Hopital Bretonneau Recruiting
Tours, France
Contact: Pierre Jean Pisella, MD         
Principal Investigator: Pierre Jean Pisella, MD         
Spain
Instituto Oftalmologico Fernandez-Vega Recruiting
Madrid, Spain
Contact: Jésus MERAYO LLOVES, MD         
Principal Investigator: Jésus MERAYO LLOVES, MD         
Hospital Universitario Virgen Macarena Recruiting
Sevilla, Spain
Contact: Jesus Montero, MD       direccion@cartujavision.com   
Principal Investigator: Jesus Montero, MD         
Hospital Recoletas Campo Grande Recruiting
Valladolid, Spain
Contact: David Galaretta, MD         
Principal Investigator: David Galaretta, MD         
Sponsors and Collaborators
SIFI SpA
Investigators
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Principal Investigator: Pierre Jean Pisella, MD, Pr HOPITAL BRETONNEAU
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Responsible Party: SIFI SpA
ClinicalTrials.gov Identifier: NCT03803748    
Other Study ID Numbers: 047/SI
First Posted: January 15, 2019    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Keratoconjunctivitis Sicca
Dry Eye Syndromes
Syndrome
Disease
Pathologic Processes
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Keratitis
Corneal Diseases
Lacrimal Apparatus Diseases