Dry Eye SyndromesPhase 4NCT01280110
The Effects of BAK on the Blood Aqueous Barrier of Pseudophakic Patients
A Phase 4 study testing Hydroxypropylmethylcellulose and Carboxymethylcellulose in people with Dry Eye Syndromes, run by University of Campinas, Brazil at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Dry Eye Syndromes
- What is being tested?
- Hydroxypropylmethylcellulose and Carboxymethylcellulose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteBrazil
- Study dates
- Mar 2011to Jan 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Pseudophakic eyes that underwent cataract surgery at least 6 months before.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Department of Ophthalmology, University of Campinas
Campinas, São Paulo
About this study
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.
Read the 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.
- Conditions
- Dry Eye Syndromes
- Being tested
- Hydroxypropylmethylcellulose, Carboxymethylcellulose
- Keywords
- dry eye, pseudophakia, cornea, lubricating drop, BAK, blood aqueous barrier, blood-retina barrier
- Medical subject headings
- Dry Eye Syndromes, Pseudophakia, Corneal Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxypropylmethylcelluloseDrug
Also called Retin Active
22 patients will receive this lubricating drop 4 times a day for 1 month
CarboxymethylcelluloseDrug
Also called Optive UD
22 patients will receive this lubricating drop 4 times a day for 1 month.
| Study group | Role | What they receive |
|---|---|---|
| Preserved (BAK 0.006%) lubricating drop | Active comparator | One group will receive preserved lubricating drops 4 times a day for 1 month. Receives: Drug: Hydroxypropylmethylcellulose |
| Preservative-free lubricating drops | Active comparator | The second group will receive preservative-free lubricating drops 4 times a day for 1 month. Receives: Drug: Carboxymethylcellulose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Aqueous Humor Flare
Aqueous humor flare indicates the degree of a break in the blood-aqueous barrier. It is objectively measured with a Laser flare meter.
Measured: Baseline, 15 days and 30 days.
Secondary outcomes (1)
Macular Thickness
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.
Measured: Baseline, 15 days and 30 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2011 (estimated)
- Study startMar 2011
- Primary completionDec 2011
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Dry Eye SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Campinas, Brazil
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Vital Paulino Costa, University of Campinas, Brazil
- Investigators
- Vital P Costa, MD, Principal investigator, Department of Ophthalmology, University of Campinas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01280110
- Sponsor's protocol ID
- VPC1
- Status last verified
- Jul 2012
- First submitted
- 18 Jan 2011
- Last updated
- 18 Jul 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Baudouin C, Labbe 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.
PubMed 20302969Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004 Jul;23(5):490-6. doi: 10.1097/01.ico.0000116526.57227.82.
PubMed 15220734Ammar 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.
PubMed 20931366
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of BAK on the Blood Aqueous Barrier of Pseudophakic Patients
- ClinicalTrials.gov ID
- NCT01280110
- Acronym / sponsor ID
- VPC1
- Conditions
- Dry Eye Syndromes
- Keywords
- dry eye, pseudophakia, cornea, lubricating drop, BAK, blood aqueous barrier, blood-retina barrier
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of Campinas, BrazilUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 20 Jan 2011 (estimated)
- Results
- Posted 12 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Preserved (BAK 0.006%) lubricating drop | Active comparator | Drug: HydroxypropylmethylcelluloseOne group will receive preserved lubricating drops 4 times a day for 1 month. |
| Preservative-free lubricating drops | Active comparator | Drug: CarboxymethylcelluloseThe second group will receive preservative-free lubricating drops 4 times a day for 1 month. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Pseudophakic eyes that underwent cataract surgery at least 6 months before.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxypropylmethylcelluloseAlso: Retin Active22 patients will receive this lubricating drop 4 times a day for 1 month | Drug | Preserved (BAK 0.006%) lubricating drop |
| CarboxymethylcelluloseAlso: Optive UD22 patients will receive this lubricating drop 4 times a day for 1 month. | Drug | Preservative-free lubricating drops |
Primary outcome
Aqueous Humor Flare
Time frame: 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.
1 secondary outcome
Macular Thickness
Time frame: Baseline, 15 days and 30 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20302969Baudouin C, Labbe 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.
- Background: PubMed 15220734Noecker RJ, Herrygers LA, Anwaruddin R. Corneal and conjunctival changes caused by commonly used glaucoma medications. Cornea. 2004 Jul;23(5):490-6. doi: 10.1097/01.ico.0000116526.57227.82.
- Background: PubMed 20931366Ammar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vital P Costa, MD principal investigator
Department of Ophthalmology, University of Campinas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxypropylmethylcellulose and Carboxymethylcellulose in people with Dry Eye Syndromes, run by University of Campinas, Brazil at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Aqueous Humor Flare (time frame: Baseline, 15 days and 30 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01280110, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2012.