A Non-inferiority Study of Eyestil® Plus Multidose Versus Vismed Multi®

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

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.

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.

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).