To Compare Blephapad Combo vs Standard Treatment for Eyelid Cleansing in Bilateral Posterior Blepharitis

• Sponsor: NTC srl (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03301844
• Collaborator: (none)
• Enrollment: 19
• Location: 1
• Arms: 2
• Actual Duration (Months): 8.9
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of, and patient satisfaction with Blephapad Combo in the treatment of posterior blepharitis.

Condition or Disease	Intervention/Treatment	Phase
Bilateral Blepharitis (Disorder)	Combination Product: Blephapad Combo; Other: Standard treatment	N/A

Detailed Description

Blepharitis is the most common condition in patients seeking an eye examination due to discomfort or eye irritation. Treatment of blepharitis is recommended even in mild cases as chronic inflammation may cause permanent damage to the Meibomian glands.

Each eye of each patient represents an experimental unit. Each patient will apply Blephapad Combo to one eye and standard treatment to the other eye in accordance with the randomization procedure.

The aim of this randomized, controlled study with a closed sequential design is to evaluate versus standard treatment the efficacy of, and patient satisfaction with Blephapad Combo in the treatment of posterior blepharitis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: A randomized, controlled study with a closed sequential designA randomized, controlled study with a closed sequential design
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized, Controlled Study With a Closed Sequential Design to Compare the Efficacy, Safety and Patient Satisfaction of Blephapad Combo vs. Standard Treatment for Eyelid Cleansing in Patients Affected by Bilateral Posterior Blepharitis.
• Actual Study Start Date: May 15, 2017
• Actual Primary Completion Date: Feb 9, 2018
• Actual Study Completion Date: Feb 9, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study treatment Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics.	Combination Product: Blephapad Combo; Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.
Other: Standard treatment Wet, warm gauze twice daily for one month.	Other: Standard treatment; Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.

Outcome Measures

Primary Outcome Measures

1. Percentage Change of the Total Score of the Grading Scales for Meibomian Gland Dysfunction (MGD) [from baseline to week 4]

   The total score of the meibomian gland dysfunction (MGD) grading scale was automatically computed by the system as the sum of the six sub-scores (i.e. Lid margin findings of vascularity, Plugging of gland orifices, Lid margin irregularity, Lid margin thickening, Partial glands and Gland dropout), ranging from 0 to 15, where higher values rapresent a worse outcome. The first four parameters were evaluated using photographic images of anterior segments, while the last two were evaluated using infrared images of the meibomian glands Based on the percentage change from baseline to week 4 of the total score of MGD score, Investigators will choose which of the two eyes had a better change of clinical features.

Secondary Outcome Measures

1. Change of the Total Score of the Grading Scales for Meibomian Gland Dysfunction (Improved vs Not Improved) [From Visit 2 (baseline) to Visit 3 (week 4)]

   For each eye change from baseline to week 4 in the total score of Meibomian Gland Dysfunction was also expressed as one of the following outcomes: Eye on Blephapad Combo: Improved-Eye on Standard: Improved Eye on Blephapad Combo: Improved-Eye on Standard: NOT Improved Eye on Blephapad Combo: NOT Improved-Eye on Standard: Improved Eye on Blephapad Combo: NOT Improved-Eye on Standard: NOT Improved The total score was automatically computed by the system as the sum of the six sub-scores (i.e. Lid margin findings of vascularity, Plugging of gland orifices, Lid margin irregularity, Lid margin thickening, Partial glands and Gland dropout), ranging from 0 to 15 (higher values rapresent a worse outcome).If the change of the total score was positive or equal to 0 the specific eye was referred as "NOT improved",on the contrary if the change of the total score resulted negative the specific eye was referred as "Improved". For each patient the results on the two eyes were combined.

2. Number of Patients Preferring the Standard or the Study Treatment (i.e. Answers to a Specific Question on Patient Preference: Study Drug vs. Standard Treatment) [at Visit 3 (week 4)]

   At the end of study patients was asked to state their preference on the treatments used.

Other Outcome Measures

1. Incidence of Ocular Adverse Events Reported Throughout the Study [From Visit 2 (baseline) to Visit 3 (week 4)]

   A targeted physical examination was performed at all visits and monitoring for ocular and systemic adverse events occurred throughout the study

2. Compliance to Treatment Evaluated by Counting the Applications (Wet Wipes) to Each Eyes [From Visit 2 (baseline) to Visit 3 (week 4)]

   Adherence to treatment was evaluated at Visit 3 by counting given wipes/gauze and unused/lost/damaged wipes/gauze. The compliance to treatment was evaluated by counting given wipes/gauze and unused/lost/damaged wipes/gauze. The following formula was applied: (Given wipes/gauze - (sum of unused/lost/damaged wipes/gauze)) / Expected number of wipes/gauze used) x 100. Where the "given wipes/gauze" were 60 and the "expected number of wipes/gauze used" were 2 per days per 4 weeks = 56.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age > 40 years

• Male or female

• Diagnosis of bilateral posterior blepharitis

• Written informed consent of patient

Exclusion Criteria:

• Treatment with topical ophthalmic drugs (artificial tears allowed)

• Ocular surgery in the previous 6 months

• Pregnant or breastfeeding women

• Alcohol abuse

• Psychiatric disorders

• Cognitive impairment that could affect evaluation of preferences

• Participation in other clinical studies in the last month

• Hypersensitivity to one or more components of the study products

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O.U. Policlinico Mater Domini	Catanzaro	CZ	Italy	88100

Sponsors and Collaborators

• NTC srl

Investigators

• Principal Investigator: Vincenzo Scorcia, A.O.U. Policlinico Mater Domini

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 19, 2017

More Information

Publications

None provided.

• Responsible Party: NTC srl
• ClinicalTrials.gov Identifier: NCT03301844
• Other Study ID Numbers: BLEPHA 01-2017
• First Posted: Oct 4, 2017
• Last Update Posted: Dec 19, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Blepharitis; Meibomian Gland Dysfunction

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between May 2017 and January 2018 at the Ophthalmology Unit of the Magna Graecia University of Catanzaro in Italy
Pre-assignment Detail	During a 2-week run-in period starting at Visit 1, and after the patient has provided informed consent, the Investigator will collect demographic data and medical history and perform a physical examination of the patient.

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Period Title: Overall Study
STARTED	19	19
COMPLETED	18	18
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Study Treatment	Standard Treatment	Total
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.	Total of all reporting groups
Overall Participants	18	18	18
Overall eyes	18	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 27.8%	5 27.8%	10 55.6%
>=65 years	13 72.2%	13 72.2%	26 144.4%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.9 (9.03)	66.9 (9.03)	66.9 (9.03)
Sex: Female, Male (Count of Participants)
Female	9 50%	9 50%	18 100%
Male	9 50%	9 50%	18 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	18 100%	18 100%	36 200%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	18 100%	18 100%	18 100%
Meibomian Gland Dysfunction (MGD) at baseline (visit 2) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	9.17 (2.64)	9.39 (2.73)	9.28 (2.65)

Outcome Measures

1. Primary Outcome

Title	Percentage Change of the Total Score of the Grading Scales for Meibomian Gland Dysfunction (MGD)
Description	The total score of the meibomian gland dysfunction (MGD) grading scale was automatically computed by the system as the sum of the six sub-scores (i.e. Lid margin findings of vascularity, Plugging of gland orifices, Lid margin irregularity, Lid margin thickening, Partial glands and Gland dropout), ranging from 0 to 15, where higher values rapresent a worse outcome. The first four parameters were evaluated using photographic images of anterior segments, while the last two were evaluated using infrared images of the meibomian glands Based on the percentage change from baseline to week 4 of the total score of MGD score, Investigators will choose which of the two eyes had a better change of clinical features.
Time Frame	from baseline to week 4

Outcome Measure Data

Analysis Population Description

patients with symmetrical bilateral posterior blepharitis

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Measure Participants	18	18
Mean (Standard Deviation) [percentage of change in the total score]	-38.5 (21.3)	-29.9 (17.6)

2. Secondary Outcome

Title	Change of the Total Score of the Grading Scales for Meibomian Gland Dysfunction (Improved vs Not Improved)
Description	For each eye change from baseline to week 4 in the total score of Meibomian Gland Dysfunction was also expressed as one of the following outcomes: Eye on Blephapad Combo: Improved-Eye on Standard: Improved Eye on Blephapad Combo: Improved-Eye on Standard: NOT Improved Eye on Blephapad Combo: NOT Improved-Eye on Standard: Improved Eye on Blephapad Combo: NOT Improved-Eye on Standard: NOT Improved The total score was automatically computed by the system as the sum of the six sub-scores (i.e. Lid margin findings of vascularity, Plugging of gland orifices, Lid margin irregularity, Lid margin thickening, Partial glands and Gland dropout), ranging from 0 to 15 (higher values rapresent a worse outcome).If the change of the total score was positive or equal to 0 the specific eye was referred as "NOT improved",on the contrary if the change of the total score resulted negative the specific eye was referred as "Improved". For each patient the results on the two eyes were combined.
Time Frame	From Visit 2 (baseline) to Visit 3 (week 4)

Outcome Measure Data

Analysis Population Description

Patiens with symmetrical bilateral posterior blepharitis who applied treatment at least once in one eye and had a baseline evaluation of the primary efficacy endpoint.

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Measure Participants	18	18
Eye improved	16 88.9%	15 83.3%
Eye NOT improved	1 5.6%	2 11.1%
Missing	1 5.6%	1 5.6%

3. Secondary Outcome

Title	Number of Patients Preferring the Standard or the Study Treatment (i.e. Answers to a Specific Question on Patient Preference: Study Drug vs. Standard Treatment)
Description	At the end of study patients was asked to state their preference on the treatments used.
Time Frame	at Visit 3 (week 4)

Outcome Measure Data

Analysis Population Description

Patiens with symmetrical bilateral posterior blepharitis who applied treatment at least once in one eye and had a baseline evaluation of the primary efficacy endpoint. One patient didn't express the preference therefore 17 patients were considered.

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Measure Participants	17	17
Count of Participants [Participants]	12 66.7%	5 27.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Treatment, Standard Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.071
	Comments
	Method	Chi-squared
	Comments
Other Statistical Analysis		Patient preference for one of the two treatments at Visit 3 was presented overall in terms of number and percentage of patients preferring the standard or the study treatment. Patient preference was compared between the standard and the study treatment with a Chi-Square test for equal proportion.

4. Other Pre-specified Outcome

Title	Incidence of Ocular Adverse Events Reported Throughout the Study
Description	A targeted physical examination was performed at all visits and monitoring for ocular and systemic adverse events occurred throughout the study
Time Frame	From Visit 2 (baseline) to Visit 3 (week 4)

Outcome Measure Data

Analysis Population Description

Patiens with symmetrical bilateral posterior blepharitis who applied treatment at least once in one eye. One patient reported a treatment-emergent systemic adverse event, i.e. "Suspected colon cancer" of mild severity that led to permanent treatment discontinuation.

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Measure Participants	18	18
Eyes with Serious Ocular Adverse Event	0 0%	0 0%
Eyes with Ocular Adverse Event	8 44.4%	7 38.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Treatment, Standard Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7353
	Comments
	Method	Chi-squared
	Comments
Other Statistical Analysis		The incidence of all the treatment-emergent systemic Adverse Events recorded in the eCRF was presented overall at patient level; the incidence of all the treatment-emergent ocular Adverse Events recorded in eCRF was presented by treatment group at eye level. Incidence of treatment-emergent ocular Adverse Events was compared between treatment groups by means of a Chi-square test.

5. Other Pre-specified Outcome

Title	Compliance to Treatment Evaluated by Counting the Applications (Wet Wipes) to Each Eyes
Description	Adherence to treatment was evaluated at Visit 3 by counting given wipes/gauze and unused/lost/damaged wipes/gauze. The compliance to treatment was evaluated by counting given wipes/gauze and unused/lost/damaged wipes/gauze. The following formula was applied: (Given wipes/gauze - (sum of unused/lost/damaged wipes/gauze)) / Expected number of wipes/gauze used) x 100. Where the "given wipes/gauze" were 60 and the "expected number of wipes/gauze used" were 2 per days per 4 weeks = 56.
Time Frame	From Visit 2 (baseline) to Visit 3 (week 4)

Outcome Measure Data

Analysis Population Description

Patiens with symmetrical bilateral posterior blepharitis who applied treatment at least once in one eye.

Arm/Group Title	Study Treatment	Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.	Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
Measure Participants	18	18
Mean (Standard Deviation) [percentage of Application (Wet Wipes)]	96.1 (8.8)	94.2 (9.5)

Adverse Events

Time Frame	from baseline to week 4
Adverse Event Reporting Description	The patient will be given a diary on which to record the application of all morning and evening treatments, as well as any adverse events occurred. The diary is to be returned at Visit 3 for review
Arm/Group Title	Study Treatment		Standard Treatment
Arm/Group Description	Blephapad Combo twice daily for one month. Blephapad is a disposable wet wipe containing Hy-Ter® solution (sodium hyaluronate acid and 4-terpineol), aloe, natural anti-inflammatories and antiseptics. Blephapad Combo: Blephapad Combo is used to cleanse, soften, sooth and decongest inflamed eyelids and cilia. The combo also presents an applicator with a heatable tablet that is applied to the eyelid in order to clean and open occluded Meibomian glands, thereby allowing the production of lipids necessary for a healthy tear film. The heatable tablet is to be used prior to cleansing with Blephapad wipes.		Wet, warm gauze twice daily for one month. Standard treatment: Standard treatment, twice daily for one month, consisting in eyelid hygiene using wet, warm gauze.
All Cause Mortality
	Study Treatment		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	Study Treatment		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Study Treatment		Standard Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/18 (44.4%)		7/18 (38.9%)
Eye disorders
Dry eye	3/18 (16.7%)		3/18 (16.7%)
Ocular pain	4/18 (22.2%)		2/18 (11.1%)
Irritation	2/18 (11.1%)		2/18 (11.1%)
Itching or discomfort	3/18 (16.7%)		2/18 (11.1%)
Increased lacrimation	2/18 (11.1%)		1/18 (5.6%)
Conjunctival hyperaemia	1/18 (5.6%)		1/18 (5.6%)
Ocular secretions	1/18 (5.6%)		1/18 (5.6%)
Crusts on eyelid margins	1/18 (5.6%)		1/18 (5.6%)
Blurred vision	1/18 (5.6%)		0/18 (0%)
Ocular hyperaemia	2/18 (11.1%)		1/18 (5.6%)
Purulent discharge	1/18 (5.6%)		0/18 (0%)
Madarosis	0/18 (0%)		1/18 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.