Efficacy of Different Treatment Regimens With Chitosan-N- Acetylcysteine in Moderate-to-severe Dry Eye Disease

Efficacy of Different Treatment Regimens With Chitosan-N- Acetylcysteine (Lacrimera®) in Moderate-to-severe Dry Eye Disease: A Pilot Study

Aim of this pilot study is to evaluate the best treatment regime of Chitosan-N-Acetylcysteine (Lacrimera®) compared to preservative-free, Hyaluronic-acid containing eyedrops (Hylo-Vision® sine).

Study Overview

• Status: Terminated
• Conditions: Eye Diseases
• Intervention / Treatment: Device: Lacrimera; Device: Hylo-Vision

Detailed Description

The present pilot study seeks to investigate the best fitting treatment regime of moderate-to-severe DED with C-NAC compared to preservative-free, Hyaluronic-acid containing eyedrops (Hylo-Vision® sine) by applying a randomized, prospective, adaptive, controlled design.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1140
    • Vienna Institute for Research in Ocular Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age older than 22 years
• Corneal staining (marked to severe; NEI grading scale >=10)

Exclusion Criteria:

• Usage of eye drops other than lubricants (e.g. antibiotics, steroids, cyclosporin-A)
• Usage of systemic antibiotic therapy
• Any pathology of the ocular surface except dry eye disease (e.g. corneal scarring, cornea ectasia)
• Ocular surgery within prior 3 months to screening
• Preceding refractive corneal surgery (e.g. LASIK)
• Ocular injury within prior 3 months
• Ocular herpes of eye or eyelid within prior 3 months
• Active ocular infection
• Active ocular inflammation or history of chronic, recurrent ocular inflammation within prior 3 months
• Eyelid abnormalities that affect lid function
• Ocular surface abnormality that may compromise corneal integrity
• Pregnancy and nursing women (in women of childbearing age a pregnancy test will be performed before inclusion into the study)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; After enrolment into the study and randomization to the study group (V0) and baseline examinations (V1), patients will receive 1 drop of Lacrimera at the study site and will be instructed to apply one drop of C-NAC into both eyes before bedtime for the following 5 consecutive days and return for a follow-up visit after 7±1 days (V2). Patients will complete a diary describing symptoms during the day, use of Lacrimera and potential side effects until the next visit. If the NEI grading is ≤1 OR the OSDI score <20 at the next visit, treatment with Lacrimera will be discontinued and one further physical follow-up appointment will be arranged, which will take place 28±2 days after the last physical visit.	Device: Lacrimera; A new preservative-free formulation of eye drops consists of a novel biopolymer, chitosan-N-acetylcysteine (C-NAC; Lacrimera®, Croma-Pharma GmbH, Leobendorf, Austria), which electrostatically binds to the mucine layer of the tear film forming a glycocalyx-like structure.
Active Comparator: Group 2; The study days are conducted in the same way as for the study group. Patients of the control group will receive preservative-free, Hyaluronic-acid containing eyedrops (Hylo-Vision® sine) for 4 times a day as control.	Device: Hylo-Vision; Preservative-free, Hyaluronic-acid containing eyedrops (Hylo-Vision® sine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of treatment	Duration of treatment in days until objectively confirmed recovery (NEI (National Eye Institute) grading ≤1 OR OSDI (Ocular Surface Disease Index) score <20, either 7±1, 14±1, 21±1 or 28±1 days) in the study group compared to the control group.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BUT (Break Up Time)	Change in BUT (Break Up Time) at different visits in both groups. Fluorescein Break Up time is measured after instillation of 100 μl fluorescein into the inferior fornix. Using a stopwatch time after the last blink until the first break up of the tear film is recorded. Three consecutive measurements are performed, and the average is calculated. Non-invasive first and averaged BUT is measured three times and averaged afterwards using the Dry eye module build into the corneal tomography device (Sirius, CSO, Italy).	1 month
Change in NI-BUT (Non-invasive Break Up Time)	Change in NI-BUT (Non-invasive Break Up Time) at different visits in both groups. The Sirius device is a routinely used device for the detailed assessment of the cornea and the tear film. NI-BUT is assessed by monitoring placido discs (Sirius, CSO, Italy) projected onto the cornea. 3 consecutive measurements are made in every eye.	1 month
OSDI (Ocular Surface Disease Index)	OSDI (Ocular Surface Disease Index) at different visits in both groups. The OSDI Questionnaire is a standardized questionnaire to evaluate the subjective disease burden caused by dry eye syndrome. The patients answer up to 12 questions regarding their symptoms. Thereafter, the OSDI Score is calculated.	1 month
Flourescein staining / Lissamin green staining grading using the NEI Score (National Eye Institute)	Lissamin green staining at different visits in both groups using the NEI Score. Fluorescein and Lissamin green dye will be used to examine the anterior surface of the human eye. Anterior Segment Photography will be used to document the findings, which are graded using the National Eye Institute (NEI) grading scale.	1 month
Change in number of MMP-positive eyes (Matrix Metallopeptidase 9)	Change in number of MMP-positive eyes in both groups (Matrix Metallopeptidase 9). MMP-9 is an inflammatory marker of the ocular surface. InflammaDry® allows to indicate elevated levels of MMP-9 in tear fluid by microfiltration technology. Patients will be instructed to look upward, and the lower eye lid will be pulled downward gently. Samples will be collected by dabbing a tear sample collector in 6-8 locations on the palpebral conjunctiva. The test is routinely performed in our dry eye unit.	1 month

Collaborators and Investigators

• Sponsor: Vienna Institute for Research in Ocular Surgery

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): August 27, 2021
• Study Completion (Actual): August 27, 2021

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 21, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Eye Diseases; Dry Eye Syndromes
• Other Study ID Numbers: Lacrimera Efficacy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No