BAK: Effects of Anti-Glaucoma Medications on the Ocular Surface

• Sponsor: Massachusetts Eye and Ear Infirmary (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01315574
• Collaborator: Alcon Research (Industry)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 34
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the efficacy of FDA-approved Travoprost (Travatan Z) and Latanoprost (Xalatan)as anti-glaucoma treatment. Several studies indicate that glaucoma medications may be associated with decreased tear production and tear film break-up time (TBUT), and increased inflammatory cells in the conjunctiva (membrane lining of the eye lids and the covering of the eye) leading to dry eye. Normal tear film (coating of the eye) is continuous and blinking maintains the tear film continuity. If you keep your eyes open long enough without blinking, the tear film will start breaking up. Your eye will feel uncomfortable forcing you to blink. In patients with dry eyes, the tear film is unstable, and breaks up faster. Therefore the tear break up time in patients who have dry eyes is shorter.

In this study, the investigators will be comparing the two previously mentioned FDA-approved eye drops Latanoprost and Travoprost. The difference between the two medications is a preservative called benzalkonium chloride (BAK). Latanoprost contains BAK while Travoprost does not. The investigators will be comparing the efficacy of each medication in lowering IOP as well as trying to track the density of immune cells across the corneal surface by taking photos of your eye. The investigators will also be assessing whether either drop leads to symptoms of dry eye by comparing results from ocular surface exam tests such as TBUT.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: Travoprost; Drug: Latanoprost	Phase 4

Detailed Description

The purpose of the study is to compare the early effects of two anti-glaucoma eye drops on eye pressure and inflammation of the eye using a microscope. One of the eye drops contains a commonly used preservative, benzalkonium chloride (BAK), while the other is free of this preservative, instead it utilises a new ionic buffer system called SofZia. Prolonged use of BAK may be damaging to the eye surface and thus being investigated at a microscopic level in this study.

Specific aims are to assess the in vivo effect of topical BAK-containing and BAK-free prostaglandin analogue anti-glaucoma therapy on intraocular pressure (IOP), as well as on density and morphology of corneal immune cells, epithelial cells and sub-basal nerve plexus.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: In Vivo Effects of Antiglaucomatous Prostaglandin Therapy on Immune Cells, Epithelium, and Nerves of the Ocular Surface: A Laser In Vivo Confocal Microscopy Study
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Latanoprost (Xalatan) 7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma.	Drug: Latanoprost; One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.; Other Names: Xalatan
Active Comparator: Travoprost (Travatan Z) 7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma.	Drug: Travoprost; One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.; Other Names: Travatan Z

Outcome Measures

Primary Outcome Measures

1. Effectiveness in Lowering Intraocular Pressure [At the 6 month follow-up time point]

   Applanation tonometry will be used to measure patients' intraocular pressure

Secondary Outcome Measures

1. Corneal Fluorescein Staining Score [At the 6 month follow-up time point]

   Corneal Fluorescein Staining score was used in this study to quantify changes in dry eye symptoms. Corneal fluorescein staining scores range from 0 to 4 points: 0=non-staining to 4 =regional whole staining of the cornea. Higher scores indicate worse eye condition.

2. Tear Film Break-Up Time [At the 6 month follow-up time point]

   Tear Film Break-Up Time (TBUT) is a clinical test used to quantify changes in dry eye symptoms. The Tear Film Break-Up time is the number of seconds between the subjects last blink and the detection of the first dry spot in the tear film.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must be 18 years of age and may be of any race and either gender;

• Subjects must not have ever used topical prostaglandin anti-glaucomatous therapy;

• Subject has not used anti-glaucomatous treatment in the past 30 days and has not been using prescribed anti-glaucomatous medication for more than 6 months.

• Subject is using other topical anti-glaucomatous topical treatment and wants to switch to a prostaglandin (must have undergone 30 day washout period)

• The IRB Approved informed consent and the privacy document must be read, signed, and dated by the subject or legally authorized representative before enrollment. Additionally, the informed consent document must be signed and dated by the individual consenting the subject, as well as signed and dated by a witness, if applicable;

• Subjects must be generally healthy and have normal ocular health; and

• Subjects must be willing to follow the study procedures and visit schedule.

Exclusion Criteria:

• Subjects must not have known sensitivities to any ingredient in any of the test articles

• Subjects must not have any systemic or ocular disease or disorder (exc refractive error), complicating factors or structural abnormality that would negatively affect the conduct or outcome of the study:

• No prior (within 30 days of enrollment) or current ocular infections (bacterial, viral or fungal), active ocular inflammation (i.e., follicular conjunctivitis, allergic conjunctivitis, iritis), glaucoma, or preauricular lymphadenopathy.

• No clinically significant lash or lid abnormality (e.g., trichiasis, entropion or ectropion).

• No uncontrolled systemic disease or debilitating disease (e.g. cardiovascular disease, hypertension, diabetes, or cystic fibrosis.).

• No prior (within 7 days of enrollment) or current, unstable active illness (e.g., upper respiratory infection).

• Pregnant woman

• Subjects must not have history of ocular surgery/trauma within the last 6 months

• Subjects must not have used any topical ocular or systemic antibiotics within 30 days of enrollment continuing throughout the study

• Subjects must not have used any topical ocular or systemic corticosteroids within 30 days of enrollment continuing throughout the study

• Subjects must not have used immunomodulator medications within 30 days of enrollment continuing throughout the study

• Subjects must not have a immune cell density of >60/fame present at their baseline confocal scan

• Subjects must not have participated in any other ophthalmic drug or device clinical trial within 30 days of enrollment.

• Inability to cooperate with the confocal exam

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts Eye and Ear Infirmary
• Alcon Research

Investigators

• Principal Investigator: Pedram Hamrah, MD, Mass Eye and Ear Infirmary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT01315574
• Other Study ID Numbers: 11-007H
• First Posted: Mar 15, 2011
• Last Update Posted: Mar 16, 2017
• Last Verified: Jan 1, 2015

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Massachusetts Eye and Ear Infirmary: Glaucoma; Xalatan; Travatan Z; Latanoprost; Travoprost; Dry Eye
• Additional relevant MeSH terms: Glaucoma; Travoprost; Latanoprost

Study Results

Participant Flow

Recruitment Details	Participants recruited from May 2011 to June 2013

Arm/Group Title	Latanoprost (Xalatan)	Travoprost (Travatan Z)
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.	7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.
Period Title: Overall Study
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Latanoprost (Xalatan)	Travoprost (Travatan Z)	Total
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.	7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.	Total of all reporting groups
Overall Participants	7	7	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.3 (7.9)	68.3 (10.0)	66.8 (8.8)
Sex: Female, Male (Count of Participants)
Female	5 71.4%	5 71.4%	10 71.4%
Male	2 28.6%	2 28.6%	4 28.6%
Region of Enrollment (participants) [Number]
United States	7 100%	7 100%	14 100%
Central Corneal Dendritic Cell Density (cells/mm^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cells/mm^2]	126 (88)	91 (60)	109 (75)
Intraocular Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	21 (6)	22 (4)	21.5 (4.8)
Corneal Fluorescein Staining Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.6 (1.1)	1.3 (2.0)	0.9 (1.6)
Tear Break-Up Time (TBUT) (seconds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [seconds]	7.9 (2.0)	8.4 (3.7)	8.1 (2.9)

Outcome Measures

1. Primary Outcome

Title	Effectiveness in Lowering Intraocular Pressure
Description	Applanation tonometry will be used to measure patients' intraocular pressure
Time Frame	At the 6 month follow-up time point

Outcome Measure Data

Analysis Population Description

Two subjects in each arm/group did not complete 6-month follow up visit. Data was not collected and analysis not completed.

Arm/Group Title	Latanoprost (Xalatan)	Travoprost (Travatan Z)
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.	7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.
Measure Participants	5	5
Mean (Standard Deviation) [mmHg]	13.7 (2.8)	17.2 (2.7)

2. Secondary Outcome

Title	Corneal Fluorescein Staining Score
Description	Corneal Fluorescein Staining score was used in this study to quantify changes in dry eye symptoms. Corneal fluorescein staining scores range from 0 to 4 points: 0=non-staining to 4 =regional whole staining of the cornea. Higher scores indicate worse eye condition.
Time Frame	At the 6 month follow-up time point

Outcome Measure Data

Analysis Population Description

Two subjects in each arm/group did not complete 6-month follow up visit. Data was not collected and analysis not completed.

Arm/Group Title	Latanoprost (Xalatan)	Travoprost (Travatan Z)
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.	7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.
Measure Participants	5	5
Mean (Standard Deviation) [units on a scale (1-4)]	1 (1.7)	1.5 (2.2)

3. Secondary Outcome

Title	Tear Film Break-Up Time
Description	Tear Film Break-Up Time (TBUT) is a clinical test used to quantify changes in dry eye symptoms. The Tear Film Break-Up time is the number of seconds between the subjects last blink and the detection of the first dry spot in the tear film.
Time Frame	At the 6 month follow-up time point

Outcome Measure Data

Analysis Population Description

Two subjects in each arm/group did not complete 6-month follow up visit. Data was not collected and analysis not completed.

Arm/Group Title	Latanoprost (Xalatan)	Travoprost (Travatan Z)
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.	7 Patients were randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.
Measure Participants	5	5
Mean (Standard Deviation) [Seconds]	6.3 (1.7)	6.7 (3.9)

Adverse Events

Time Frame	Over the course of the 6 month study period
Arm/Group Title	Latanoprost (Xalatan)		Travoprost (Travatan Z)
Arm/Group Description	7 Patients were randomized to receive BAK-containing Xalatan for treatment of their glaucoma. Latanoprost: One drop Xalatan (0.005% ophthalmic solution) in affected eye once daily.		7 Patients were be randomized to receive BAK-free Travatan Z for treatment of their glaucoma. Travoprost: One drop Travatan Z (0.004% ophthalmic solution) in affected eye once daily.
All Cause Mortality
	Latanoprost (Xalatan)		Travoprost (Travatan Z)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Latanoprost (Xalatan)		Travoprost (Travatan Z)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Latanoprost (Xalatan)		Travoprost (Travatan Z)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)

Limitations/Caveats

Early termination due to very slow rate of recruitment, hence reduced power of the study (small sample size); some patients lost to follow-up.

More Information

Certain Agreements

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

There is NOT 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.