Back to resultsEfficacy and Safety of Topical Hydrocortisone on Signs and Symptoms of Dry Eye Associated to Meibomian Gland Dysfunction
Primary Purpose
Dry Eye, Meibomian Gland Dysfunction
Status
Recruiting
Phase
Phase 4
Locations
Spain
Study Type
Interventional
Intervention
Hydrocortisone Ophthalmic
MGD Rx EyeBag® eyelid warming device
Lephanet® lid wipes
Thealoz Duo® artificial tear with trehalose 3% and sodium hyaluronate 0.15%
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Documented diagnosis of DE defined by TBUT value ≤ 5 seconds and Schirmer I test value < 10 mm/5 min
- Normal ophthalmic findings except dry eye disease and meibomian gland dysfunction
- OSDI score > 23 (moderate symptoms)
- Documented diagnosis of MGD grade 2 to 3
- Patient who can understand the instructions and adhere to medications
- Patient who receives complete information regarding the study objectives, authorize their participation in the study and sign an informed consent form before entering in the study
Exclusion Criteria:
- Any contraindication or known allergies to Lephanet®, Thealoz Duo®, MGD Rx EyeBag® or Softacort®
- Ocular surgery in the past 6 months
- Ocular hypertension or glaucoma
- Cicatricial MGD
- Atopic condition including ocular allergy
- Suspect demodex lid infestation as evidenced by the presence of collarettes
- Intraocular inflammation
- Confirmed infection with COVID-19 in the last 3 months
- Systemic autoimmune disorder
- Use of contact lenses during the month prior to inclusion in the study or during the study
- Punctal occlusion
- Intraocular pressure > 22 mmHg
- Patient who has received topical or systemic anti-inflammatory treatments including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDS) within 3 months prior to be included in the study or with a prescription for receiving topical / systemic anti-inflammatory treatments for the next 3 months
- In the investigator´s opinion, use of systemic medications that could affect the function of the meibomian gland and tear production within 3 months prior to be included in the study
- Any ocular or systemic disease known to affect the tear film other than MGD
- Patient with any situation or state that in the opinion of the investigator discourages their participation in the study
- Patient participating in any other interventional or non-interventional study or who have participated in another study within 30 days prior to inclusion in this study
- Women who are pregnant, planning to become pregnant or breastfeeding
- Patient who will not be able to complete the study (e.g., not willing to attend the follow-up visits, way of life interfering with compliance)
Sites / Locations
- Hospital La FeRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Intervention group
Control group
Arm Description
Softacort® Lephanet® Thealoz Duo® MGD Rx EyeBag®
Lephanet® Thealoz Duo® MGD Rx EyeBag®
Outcomes
Primary Outcome Measures
Efficacy endpoint: Change from baseline in Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) at 14 days
Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) calculated by the sum of the Visual Analogue scale (VAS) score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in the following symptoms: itching, dry eye sensation, burning, foreign body sensation and ocular redness.
Safety endpoint: Incidence of increased intraocular pressure and change from baseline at Day 0, Day 14, Day 28 and Day 84
Mean of 3 measures of intraocular pressure measured with Goldmann tonometer in each eye on Day 0, Day 14, Day 28 and Day 84. Increased intraocular pressure defined as >21 mmHg.
Secondary Outcome Measures
Change from baseline in Ocular Surface Disease Index (OSDI) questionnaire at Day 14, Day 28 and Day 84
12-item questionnaire related to vision-related function, ocular symptoms, and environmental triggers of dry eye. Response on a 0 to 4 scale that ranges from "none of the time" to "all of the time". The final score is calculated by multiplying the sum of all the scores by 25 and then dividing the total by the number of questions answered. Scores range from 0 to 100 with 0 to 12 representing normal, 13 to 22 mild DED, 23 to 32 moderate DED, and 33 severe DED
Change from baseline in Meibomian Gland Dysfunction Dry Eye symptom score at Day 14, Day 28 and Day 84
Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) calculated by the sum of the VAS score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in the following symptoms: itching, dry eye sensation, burning, foreign body sensation and ocular redness.
Change from baseline in ocular symptoms Visual Analogue scale (VAS) questionnaire at Day 14, Day 28 and Day 84
VAS score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in each of the following symptoms: itching, dry eye sensation, burning, foreign body sensation, ocular redness, ocular fatigue, and blurry vision.
Change from baseline in hyperemia score (McMonnies-Chapman scale) at Day 14, Day 28 and Day 84.
Inferior conjunctival hyperemia will be estimated by comparison with the photographic conjunctival hyperemia reference scale covering six grades, with highest grade as worst hyperemia.
Change from baseline in Tear break up time (TBUT) at Day 14, Day 28 and Day 84
Number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film observed with slit-lamp after instillation of fluorescein. A TBUT under 10 seconds is considered abnormal
Change from baseline in corneal and conjunctival staining with fluorescein (Oxford grading scale) at Day 14, Day 28 and Day 84
After instillation of fluorescein in conjunctival sac a comparison to the Oxford chart panels A to E, with E being the worst outcome.
Change from baseline in corneal and conjunctival staining with lissamine green (Van Bijsterveld scale) at Day 14, Day 28 and Day 84
Scoring system that divides the ocular surface into three zones: nasal bulbar conjunctiva, temporal bulbar conjunctiva, and cornea. Each zone is evaluated on a scale of 0 to 3, with 0 indicating no staining and 3 indicating confluent staining; the maximum possible worse outcome score with this system is 9.
Change from baseline in meniscus height at Day 14, Day 28 and Day 84
Measured with anterior segment optical coherence tomography. The lower the tear meniscus height the worst outcome.
Change from baseline in Schirmer I test at Day 14, Day 28 and Day 84
Folded edge Schirmer strip is placed over the rim of the lower eyelid and the eyes are then lightly closed. The amount of wetting after 5 minutes on the strip is measured in mm. Normal more than 10 mm / 5 min
Change from baseline in MGD grading at Day 14, Day 28 and Day 84
Grading of MGD: 0 to 4 where 0 is no meibomian gland dropout and expressed meibum with clear appearance and 4 is with gland dropout of more than half the lid margin or complete keratinization of the ducts and no expression of meibum. Higher grade is a worse outcome.
Change from baseline in lid abnormalities at Day 14, Day 28 and Day 84
Lid margin irregularity (presence or absence), thickness, and plugging of the meibomian orifices. A scale from 0 to 2, with 0 = no findings, 1 = mild findings, and 2 = severe findings.
Change from baseline in Eyelid telangiectasia score at Day 14, Day 28 and Day 84
Eyelid telangiectasia score from 0 to 3, where 0 is no findings and 3 is severe findings.
Change from baseline in Lissamine green staining score at Day 14, Day 28 and Day 84
Mean of longitudinal staining of upper lid margin after instilation with lissamine green graded from 0 to 3 and sagittal staining graded from 0 to 3 estimated by comparison with standard chart. Higher grade is a worse outcome.
Change from baseline in Meibomian gland expressibility score at Day 14, Day 28 and Day 84
Express each of 5 glands in temporal, central and lower lid and grade each gland on a scale from 0 to 3, with 3 = clear liquid secretion, 2 = cloudy liquid secretion, 1 = inspissated / toothpaste consistency, and 0 = no secretion. Total score range from 0 to 45. A lower grade is a worse outcome.
Change from baseline in tear inflammatory cytokines at Day 14
Levels of 8 inflammatory cytokines in tears will be determined 2 micro liter samples taken from each eye.
Incidence of adverse events and serious adverse events occurred during the study.
Report of any untoward medical occurrence in a patient during the study
Change from baseline in ETDRS visual acuity at Day 14, Day 28 and Day 84
Best corrected visual acuity in each eye measured with the ETDRS optotype.
Full Information
NCT ID
NCT05159284
First Posted
October 25, 2021
Last Updated
December 2, 2021
Sponsor
Laboratorios Thea, Spain
1. Study Identification
Unique Protocol Identification Number
NCT05159284
Brief Title
Efficacy and Safety of Topical Hydrocortisone on Signs and Symptoms of Dry Eye Associated to Meibomian Gland Dysfunction
Official Title
Prospective Evaluation of the Efficacy and Safety of Topical Hydrocortisone Treatment on Clinical Signs and Symptoms of Dry Eye Disease Associated With Moderate Meibomian Gland Dysfunction
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 9, 2021 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
August 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Laboratorios Thea, Spain
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is assess the efficacy and safety of topical hydrocortisone (Softacort) for treatment of clinical signs and symptoms of dry eye disease when associated with moderate meibomian gland dysfunction.
Detailed Description
This is a prospective, interventional, randomized (1:1), single blind, of parallel groups and two treatment arms clinical trial (phase IV).
All patients diagnosed with dry eye disease (DED) associated with moderate MGD may participate in the study if they meet all the selection criteria.
Patients (or their representatives) will provide informed consent (IC) prior to the enrolment in the study and to the start of data collection. Patients must meet all the inclusion criteria and not meet any of the exclusion criteria.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye, Meibomian Gland Dysfunction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Phase IV, interventional, prospective, randomized, single blind, of parallel groups with two treatment arms clinical trial in one center.
Masking
Investigator
Masking Description
This is a single-blinded study for the PI or person designated to conduct the study (blinded investigator). Study medication will be labelled as blinded medication. The prescription will be done by the blinded investigator using a kit number, and study medication delivery will be done by a person designed by the PI for this topic through the study (unblinded collaborator). Patients will be instructed not to inform the investigators who perform the ophthalmological evaluation about the group they will be assigned to. Patient assessments will be performed by blinded investigator.
Allocation
Randomized
Enrollment
54 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention group
Arm Type
Experimental
Arm Description
Softacort® Lephanet® Thealoz Duo® MGD Rx EyeBag®
Arm Title
Control group
Arm Type
Other
Arm Description
Lephanet® Thealoz Duo® MGD Rx EyeBag®
Intervention Type
Drug
Intervention Name(s)
Hydrocortisone Ophthalmic
Other Intervention Name(s)
Softacort®
Intervention Description
1 drop 4 times daily for 12 days, followed by twice daily for 2 days and stop, for a total of 14 days of treatment. Repeat on day 28: 1 drop 4 times daily for 12 days, followed by twice daily for 2 days and stop. Patients in the intervention arm will receive two 14-day cycles of hydrocortisone.
Intervention Type
Device
Intervention Name(s)
MGD Rx EyeBag® eyelid warming device
Other Intervention Name(s)
Blepha EyeBag®
Intervention Description
Eyelid warming device used once daily for 10 minutes followed by lid massage for 12 weeks by patients in both control and intervention arm.
Intervention Type
Device
Intervention Name(s)
Lephanet® lid wipes
Other Intervention Name(s)
Blephaclean®
Intervention Description
Lid hygiene with Lephanet® lid wipes used twice daily for 3 weeks followed by once daily for 9 more weeks by patients in both control and intervention arm.
Intervention Type
Device
Intervention Name(s)
Thealoz Duo® artificial tear with trehalose 3% and sodium hyaluronate 0.15%
Intervention Description
Artificial tear supplementation with Thealoz Duo® 4 times daily for 12 weeks by patients in both control and intervention arm.
Primary Outcome Measure Information:
Title
Efficacy endpoint: Change from baseline in Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) at 14 days
Description
Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) calculated by the sum of the Visual Analogue scale (VAS) score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in the following symptoms: itching, dry eye sensation, burning, foreign body sensation and ocular redness.
Time Frame
Day 0 and Day 14
Title
Safety endpoint: Incidence of increased intraocular pressure and change from baseline at Day 0, Day 14, Day 28 and Day 84
Description
Mean of 3 measures of intraocular pressure measured with Goldmann tonometer in each eye on Day 0, Day 14, Day 28 and Day 84. Increased intraocular pressure defined as >21 mmHg.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Secondary Outcome Measure Information:
Title
Change from baseline in Ocular Surface Disease Index (OSDI) questionnaire at Day 14, Day 28 and Day 84
Description
12-item questionnaire related to vision-related function, ocular symptoms, and environmental triggers of dry eye. Response on a 0 to 4 scale that ranges from "none of the time" to "all of the time". The final score is calculated by multiplying the sum of all the scores by 25 and then dividing the total by the number of questions answered. Scores range from 0 to 100 with 0 to 12 representing normal, 13 to 22 mild DED, 23 to 32 moderate DED, and 33 severe DED
Time Frame
Day 0, Day 14, Day 28 and Day 84.
Title
Change from baseline in Meibomian Gland Dysfunction Dry Eye symptom score at Day 14, Day 28 and Day 84
Description
Meibomian Gland Dysfunction Dry Eye symptom score (MGD-DE) calculated by the sum of the VAS score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in the following symptoms: itching, dry eye sensation, burning, foreign body sensation and ocular redness.
Time Frame
Day 0, Day 14, Day 28 and Day 84.
Title
Change from baseline in ocular symptoms Visual Analogue scale (VAS) questionnaire at Day 14, Day 28 and Day 84
Description
VAS score assigned by the patient on a scale from 0 (no symptoms) to 100 (worst symptoms) in each of the following symptoms: itching, dry eye sensation, burning, foreign body sensation, ocular redness, ocular fatigue, and blurry vision.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in hyperemia score (McMonnies-Chapman scale) at Day 14, Day 28 and Day 84.
Description
Inferior conjunctival hyperemia will be estimated by comparison with the photographic conjunctival hyperemia reference scale covering six grades, with highest grade as worst hyperemia.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in Tear break up time (TBUT) at Day 14, Day 28 and Day 84
Description
Number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film observed with slit-lamp after instillation of fluorescein. A TBUT under 10 seconds is considered abnormal
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in corneal and conjunctival staining with fluorescein (Oxford grading scale) at Day 14, Day 28 and Day 84
Description
After instillation of fluorescein in conjunctival sac a comparison to the Oxford chart panels A to E, with E being the worst outcome.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in corneal and conjunctival staining with lissamine green (Van Bijsterveld scale) at Day 14, Day 28 and Day 84
Description
Scoring system that divides the ocular surface into three zones: nasal bulbar conjunctiva, temporal bulbar conjunctiva, and cornea. Each zone is evaluated on a scale of 0 to 3, with 0 indicating no staining and 3 indicating confluent staining; the maximum possible worse outcome score with this system is 9.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in meniscus height at Day 14, Day 28 and Day 84
Description
Measured with anterior segment optical coherence tomography. The lower the tear meniscus height the worst outcome.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in Schirmer I test at Day 14, Day 28 and Day 84
Description
Folded edge Schirmer strip is placed over the rim of the lower eyelid and the eyes are then lightly closed. The amount of wetting after 5 minutes on the strip is measured in mm. Normal more than 10 mm / 5 min
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in MGD grading at Day 14, Day 28 and Day 84
Description
Grading of MGD: 0 to 4 where 0 is no meibomian gland dropout and expressed meibum with clear appearance and 4 is with gland dropout of more than half the lid margin or complete keratinization of the ducts and no expression of meibum. Higher grade is a worse outcome.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in lid abnormalities at Day 14, Day 28 and Day 84
Description
Lid margin irregularity (presence or absence), thickness, and plugging of the meibomian orifices. A scale from 0 to 2, with 0 = no findings, 1 = mild findings, and 2 = severe findings.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in Eyelid telangiectasia score at Day 14, Day 28 and Day 84
Description
Eyelid telangiectasia score from 0 to 3, where 0 is no findings and 3 is severe findings.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in Lissamine green staining score at Day 14, Day 28 and Day 84
Description
Mean of longitudinal staining of upper lid margin after instilation with lissamine green graded from 0 to 3 and sagittal staining graded from 0 to 3 estimated by comparison with standard chart. Higher grade is a worse outcome.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in Meibomian gland expressibility score at Day 14, Day 28 and Day 84
Description
Express each of 5 glands in temporal, central and lower lid and grade each gland on a scale from 0 to 3, with 3 = clear liquid secretion, 2 = cloudy liquid secretion, 1 = inspissated / toothpaste consistency, and 0 = no secretion. Total score range from 0 to 45. A lower grade is a worse outcome.
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in tear inflammatory cytokines at Day 14
Description
Levels of 8 inflammatory cytokines in tears will be determined 2 micro liter samples taken from each eye.
Time Frame
Day 0 and Day 14.
Title
Incidence of adverse events and serious adverse events occurred during the study.
Description
Report of any untoward medical occurrence in a patient during the study
Time Frame
Day 0, Day 14, Day 28 and Day 84
Title
Change from baseline in ETDRS visual acuity at Day 14, Day 28 and Day 84
Description
Best corrected visual acuity in each eye measured with the ETDRS optotype.
Time Frame
Day 0, Day 14, Day 28 and Day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Documented diagnosis of DE defined by TBUT value ≤ 5 seconds and Schirmer I test value < 10 mm/5 min
Normal ophthalmic findings except dry eye disease and meibomian gland dysfunction
OSDI score > 23 (moderate symptoms)
Documented diagnosis of MGD grade 2 to 3
Patient who can understand the instructions and adhere to medications
Patient who receives complete information regarding the study objectives, authorize their participation in the study and sign an informed consent form before entering in the study
Exclusion Criteria:
Any contraindication or known allergies to Lephanet®, Thealoz Duo®, MGD Rx EyeBag® or Softacort®
Ocular surgery in the past 6 months
Ocular hypertension or glaucoma
Cicatricial MGD
Atopic condition including ocular allergy
Suspect demodex lid infestation as evidenced by the presence of collarettes
Intraocular inflammation
Confirmed infection with COVID-19 in the last 3 months
Systemic autoimmune disorder
Use of contact lenses during the month prior to inclusion in the study or during the study
Punctal occlusion
Intraocular pressure > 22 mmHg
Patient who has received topical or systemic anti-inflammatory treatments including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDS) within 3 months prior to be included in the study or with a prescription for receiving topical / systemic anti-inflammatory treatments for the next 3 months
In the investigator´s opinion, use of systemic medications that could affect the function of the meibomian gland and tear production within 3 months prior to be included in the study
Any ocular or systemic disease known to affect the tear film other than MGD
Patient with any situation or state that in the opinion of the investigator discourages their participation in the study
Patient participating in any other interventional or non-interventional study or who have participated in another study within 30 days prior to inclusion in this study
Women who are pregnant, planning to become pregnant or breastfeeding
Patient who will not be able to complete the study (e.g., not willing to attend the follow-up visits, way of life interfering with compliance)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Beatriz Greaves, Dr
Phone
+34934766810
Ext
126
Email
maría.greaves@theapharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ana Hervas Ontiveros, Dr
Organizational Affiliation
anheront@gmail.com
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Hervas, MD
Phone
+34 961244063
Email
fom@gva.es
12. IPD Sharing Statement
Plan to Share IPD
No
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Efficacy and Safety of Topical Hydrocortisone on Signs and Symptoms of Dry Eye Associated to Meibomian Gland Dysfunction
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