Dry Eye Syndromes047/SINCT03803748
A Non-inferiority Study of Eyestil® Plus Multidose Versus Vismed Multi®
A study testing Eyestil Plus® in people with Dry Eye Syndromes, run by SIFI SpA at 12 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dry Eye Syndromes
- What is being tested?
- Eyestil Plus®
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 17 Jul 2019to 31 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 14Show fewer
- 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).
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
France9 sites
CHU de Bordeaux - Hôpital Pellegrin
Bordeaux
Chu Morvan
Brest
CHU François Mitterand
Dijon
Hôpital de la Croix Rousse
Lyon
Centre Monticelli
Marseille
Hopital La Timone Adultes
Marseille
CHU de Nice - Hôpital Pasteur
Nice
CHU Saint Etienne/Hôpital Nord
Saint-Etienne
Hopital Bretonneau
Tours
Spain3 sites
Instituto Oftalmologico Fernandez-Vega
Madrid
Hospital Universitario Virgen Macarena
Seville
Hospital Recoletas Campo Grande
Valladolid
About this study
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
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.
Read the 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.
- Conditions
- Dry Eye Syndromes
- Being tested
- Eyestil Plus®
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eyestil Plus®Device
- 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
| Study group | Role | What they receive |
|---|---|---|
| Eyestil Plus® | Experimental | 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, Receives: Device: Eyestil Plus® |
| Vismed | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint/clinical performance by Oxford scale
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
Measured: between Day 1 and Day 35 ±4
Secondary outcomes (7)
secondary endpoint/clinical performance by TBUT test
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).
Measured: between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7
secondary endpoint/clinical performance by Oxford scale
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
Measured: between Day 1 and Day 84 ±7 days
secondary endpoint/clinical performance by Schirmer Test
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).
Measured: test between Day 1 and Day 84 ±7
secondary endpoint/patient symptoms by Ocular Symptoms Disease Index (OSDI) score
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.
Measured: Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7
secondary endpoint/patient symptoms by Dry Eye-Related Quality -of-Life(DEQS) questionnaire
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
Measured: Day 1 and Day 35 ±4 and [Day 1 and Day 84 ±7
secondary endpoint/safety
The description of all adverse events, related and unrelated to the medical devices, anticipated or unanticipated.
Measured: Day 1 and Day 84 ±7
secondary endpoint/Investigator overall treatment satisfaction using by a four-point scale
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.
Measured: Day 35±4 and Day 84 ±7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2019
- Study start17 Jul 2019
- Primary completion2 May 2022
- Study completion31 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dry Eye SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a national, prospective, multicenter, comparative, randomized, double-blinded non-inferiority study performed in two parallel groups.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- SIFI SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pierre Jean Pisella, MD, Pr, Principal investigator, HOPITAL BRETONNEAU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03803748
- Sponsor's protocol ID
- 047/SI
- Acronym
- 047/SI
- Status last verified
- May 2022
- First submitted
- 19 Dec 2018
- Last updated
- 23 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03803748
- Acronym / sponsor ID
- 047/SI / 047/SI
- Conditions
- Dry Eye Syndromes
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- SIFI SpAIndustry (pharma, biotech, devices)
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 2 May 2022 (actual)
- Study completion
- 31 Aug 2022 (actual)
- First posted
- 15 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This is a national, prospective, multicenter, comparative, randomized, double-blinded non-inferiority study performed in two parallel groups.
| Arm | Type | Receives |
|---|---|---|
| Eyestil Plus® | Experimental | Device: 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, |
| Vismed | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Device | Eyestil Plus® |
Primary outcome
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
7 secondary outcomes
secondary endpoint/clinical performance by TBUT test
Time frame: between Day 1 and Day 35 ±4 and Day 1 and Day 84 ±7
secondary endpoint/clinical performance by Oxford scale
Time frame: between Day 1 and Day 84 ±7 days
secondary endpoint/clinical performance by Schirmer Test
Time frame: test between Day 1 and Day 84 ±7
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
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
secondary endpoint/safety
Time frame: Day 1 and Day 84 ±7
secondary endpoint/Investigator overall treatment satisfaction using by a four-point scale
Time frame: Day 35±4 and Day 84 ±7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pierre Jean Pisella, MD, Pr principal investigator
HOPITAL BRETONNEAU
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Eyestil Plus® in people with Dry Eye Syndromes, run by SIFI SpA at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint/clinical performance by Oxford scale (time frame: between Day 1 and Day 35 ±4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2022.