The Effects of BAK on the Blood Aqueous Barrier of Pseudophakic Patients

• Sponsor: University of Campinas, Brazil (Other)
• Overall Status: Completed
• CT.gov ID: NCT01280110
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 44
• Location: 1
• Arms: 2
• Duration (Months): 10.1
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

BAK is one of the most frequent preservatives in eye drops. BAK is a quaternary ammonium salt with surfactant qualities. It can be bacteriostatic or bactericidal depending on the concentrations used. It has been shown to be effective against most bacteria with a few exceptions, such as Pseudomonas aeruginosa, or picornaviruses. It as been widely used in eyedrops, nose sprays, hand and face washes, mouthwashes, spermicidal creams, and in various other cleaners, sanitizers, and disinfectants. BAK gained popularity when it was first introduced because it also enhances corneal penetration of some drugs by causing epithelial separation.

It is present in several ophthalmic formulations, including most of the antiglaucoma medications. If used chronically, BAK has been found to cause ocular surface changes, such as dry eye and punctuate keratitis. BAK has also been suggested to promote a break in the blood aqueous barrier, which may lead to undesirable consequences, such as uveitis and cystoid macular edema. However, this information is controversial. The purpose of this study is to evaluate the consequences of BAK on the blood-retinal and blood-aqueous barriers of pseudophakic patients receiving BAK-preserved lubricating drops.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndromes	Drug: Hydroxypropylmethylcellulose; Drug: Carboxymethylcellulose	Phase 4

Detailed Description

The primary hypothesis behind the study is that BAK may lead to a break in the blood-retina barrier in pseudophakic eyes, leading to an increase in macular thickness, compared to a non-BAK containing solution. The secondary hypothesis is that solutions containing BAK will increase the permeability of the blood aqueous barrier compared to non-BAK solutions. If the hypotheses are confirmed, they may serve as a contraindication to the use of BAK-preserved drops in pseudophakic eyes requiring chronic use of medications.

This is a prospective, randomized, examiner-masked, controlled study involving 44 pseudophakic eyes of 44 patients. Patients receiving any other eyedrop, with a previous history of uveitis, posterior capsule rupture or any other ophthalmic surgery will be excluded. Patients will be randomized to the use of a BAK-preserved lubricating drop or to the use of a non-preserved lubricating drop q.i.d for one month. Effects on the blood aqueous barrier will be objectively measured with a laser flare meter (Kowa, Japan) at baseline, 15 days and one month after inclusion. Patients will also have OCT images (Cirrus, Zeiss, USA) of the macula at the same time intervals to evaluate the possible effects on the blood-retina barrier. Macular thickness and the presence of cystoid macular edema will be evaluated at each time interval.

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: The Effects of BAK on the Blood Aqueous Barrier of Pseudophakic Patients
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Preserved (BAK 0.006%) lubricating drop One group will receive preserved lubricating drops 4 times a day for 1 month.	Drug: Hydroxypropylmethylcellulose; 22 patients will receive this lubricating drop 4 times a day for 1 month; Other Names: Retin Active
Active Comparator: Preservative-free lubricating drops The second group will receive preservative-free lubricating drops 4 times a day for 1 month.	Drug: Carboxymethylcellulose; 22 patients will receive this lubricating drop 4 times a day for 1 month.; Other Names: Optive UD

Outcome Measures

Primary Outcome Measures

1. Aqueous Humor Flare [Baseline, 15 days and 30 days.]

   Aqueous humor flare indicates the degree of a break in the blood-aqueous barrier. It is objectively measured with a Laser flare meter.

Secondary Outcome Measures

1. Macular Thickness [Baseline, 15 days and 30 days.]

   Macular thickness will be measured with an Optical coherence tomography (OCT). Measures 5% under the normal population according to the OCT software will be considered break in the blood-retina barrier.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Pseudophakic eyes that underwent cataract surgery at least 6 months before.

Exclusion Criteria:

• Use of any eyedrop.

• Other conditions associated with a break in the blood-aqueous or blood retina barrier (ie diabetes, ARMD, vasculitis, uveitis)

• Previous history of cystoid macular edema.

• Previous ocular surgery other than cataract surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Ophthalmology, University of Campinas	Campinas	SP	Brazil

Sponsors and Collaborators

• University of Campinas, Brazil
• Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Vital P Costa, MD, Department of Ophthalmology, University of Campinas

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ammar DA, Noecker RJ, Kahook MY. Effects of benzalkonium chloride-preserved, polyquad-preserved, and sofZia-preserved topical glaucoma medications on human ocular epithelial cells. Adv Ther. 2010 Nov;27(11):837-45. doi: 10.1007/s12325-010-0070-1. Epub 2010 Oct 7.
• Baudouin C, Labbé A, Liang H, Pauly A, Brignole-Baudouin F. Preservatives in eyedrops: the good, the bad and the ugly. Prog Retin Eye Res. 2010 Jul;29(4):312-34. doi: 10.1016/j.preteyeres.2010.03.001. Epub 2010 Mar 17.
• Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004 Jul;23(5):490-6.

• Responsible Party: Vital Paulino Costa, Professor of Ophthalmology, University of Campinas, Brazil
• ClinicalTrials.gov Identifier: NCT01280110
• Other Study ID Numbers: VPC1
• First Posted: Jan 20, 2011
• Last Update Posted: Jul 18, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Vital Paulino Costa, Professor of Ophthalmology, University of Campinas, Brazil: dry eye; pseudophakia; cornea; lubricating drop; BAK; blood aqueous barrier; blood-retina barrier
• Additional relevant MeSH terms: Dry Eye Syndromes; Carboxymethylcellulose Sodium

Study Results

Participant Flow

Recruitment Details	Recruitment period started on March 2011 through December 2011 in the Department of Ophthalmology at the Hospital das Clínicas - State University of Campinas.

Arm/Group Title	Preserved (BAK 0.006%) Lubricating Drop	Preservative-free Lubricating Drops
Arm/Group Description	One group will receive preserved lubricating drops 4 times a day for 1 month.	The second group will receive preservative-free lubricating drops 4 times a day for 1 month.
Period Title: Overall Study
STARTED	22	22
COMPLETED	22	22
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Preserved (BAK 0.006%) Lubricating Drop	Preservative-free Lubricating Drops	Total
Arm/Group Description	One group will receive preserved lubricating drops 4 times a day for 1 month.	The second group will receive preservative-free lubricating drops 4 times a day for 1 month.	Total of all reporting groups
Overall Participants	22	22	44
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	6 27.3%	7 31.8%	13 29.5%
>=65 years	16 72.7%	15 68.2%	31 70.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (10.7)	65.2 (12.2)	67.1 (11.5)
Sex: Female, Male (Count of Participants)
Female	9 40.9%	13 59.1%	22 50%
Male	13 59.1%	9 40.9%	22 50%
Region of Enrollment (participants) [Number]
Brazil	22 100%	22 100%	44 100%

Outcome Measures

1. Primary Outcome

Title	Aqueous Humor Flare
Description	Aqueous humor flare indicates the degree of a break in the blood-aqueous barrier. It is objectively measured with a Laser flare meter.
Time Frame	Baseline, 15 days and 30 days.

Outcome Measure Data

Analysis Population Description

Statiscal power of 80%.

Arm/Group Title	Preserved (BAK 0.006%) Lubricating Drop	Preservative-free Lubricating Drops
Arm/Group Description	One group will receive preserved lubricating drops 4 times a day for 1 month. The flare will be evaluated with Laser Flare Cell Meter (Kowa, FM 500, Japan). The patients will have 3 evaluations (baseline, 15 days and 30 days). The baseline measure is done before the use of the eyedrops.	he second group will receive preservative-free lubricating drops 4 times a day for 1 month. The flare will be evaluated with Laser Flare Cell Meter (Kowa, FM 500, Japan). The patients will have 3 evaluations (baseline, 15 days and 30 days). The baseline measure is done before the use of the eyedrops.
Measure Participants	22	22
Baseline	8.4 (2.7)	9.3 (2.6)
15 days	11.4 (5.1)	8.4 (2.8)
30 days	11.9 (5.9)	8.4 (2.5)

2. Secondary Outcome

Title	Macular Thickness
Description	Macular thickness will be measured with an Optical coherence tomography (OCT). Measures 5% under the normal population according to the OCT software will be considered break in the blood-retina barrier.
Time Frame	Baseline, 15 days and 30 days.

Outcome Measure Data

Analysis Population Description

Statiscal power of 80%

Arm/Group Title	Preserved (BAK 0.006%) Lubricating Drop	Preservative-free Lubricating Drops
Arm/Group Description	One group will receive preserved lubricating drops 4 times a day for 1 month. The central macular thickness was obtained through Cirrus™ HD-OCT (Zeiss). Mode 512x128 macular cube scan	The second group will receive preservative-free lubricating drops 4 times a day for 1 month. The central macular thickness was obtained through Cirrus™ HD-OCT (Zeiss). Mode 512x128 macular cube scan
Measure Participants	22	22
Baseline	258.5 (26.7)	259.2 (26.8)
15 days	254.9 (24.2)	256.4 (27.6)
30 days	255.9 (25.1)	258.3 (29.1)

Adverse Events

Arm/Group Title	Preserved (BAK 0.006%) Lubricating Drop		Preservative-free Lubricating Drops
Arm/Group Description	One group will receive preserved lubricating drops 4 times a day for 1 month.		The second group will receive preservative-free lubricating drops 4 times a day for 1 month.
All Cause Mortality
	Preserved (BAK 0.006%) Lubricating Drop		Preservative-free Lubricating Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Preserved (BAK 0.006%) Lubricating Drop		Preservative-free Lubricating Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Preserved (BAK 0.006%) Lubricating Drop		Preservative-free Lubricating Drops
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

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.