Inflammation, Pseudophakia
Conditions
Keywords
NSAID, Ocular Inflammation, bromfenac
Brief summary
This is a single-center, randomized, investigator-masked, parallel group, and active-comparator controlled study investigating the clinical outcomes for visual acuity and macular thickness after treatment with Bromday (bromfenac ophthalmic solution) 0.09% QD or Nevanac (nepafenac ophthalmic suspension) 0.1% TID in subjects who have undergone cataract extraction with posterior chamber intraocular lens implantation.
Detailed description
Two topical NSAIDs currently approved for postoperative treatment of pain and inflammation in cataract surgery are bromfenac 0.09% and nepafenac 0.1%. Both purport to treat ocular inflammation by acting as a potent inhibitor of COX-1 and COX-2 enzymes. Clinical studies to date lack clarity on which topical NSAID may be the most efficacious.
Interventions
Sponsors
Bausch & Lomb Incorporated
Toyos Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are male or female at least 18 years of age who are scheduled for unilateral cataract surgery (phacoemulsification or extracapsular) with posterior chamber intraocular lens implantation and for whom no other ophthalmic surgical procedures (e.g., relaxing incisions, iridectomy, conjunctival excisions, etc) are to be conducted during the cataract surgery. * Agree not to have any other ocular surgical procedures in the study or fellow (non study) eye within 15 days prior to the initiation of dosing with the test article or throughout the duration of the study. * Have a Best Corrected Visual Acuity of 20/200 or better in either eye. * If a woman capable of becoming pregnant, agree to have urine pregnancy testing performed at screening (must be negative) and agree to use a medically acceptable form of birth control throughout the study duration and for at least one week prior to and after completion of the study. Women considered capable of becoming pregnant include all females who have experienced menarche and who have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). * Have IOP ≥ 5 mmHg and ≤ 22 mmHg (in study eye) with or without anti glaucoma therapy at the pre operative screening visit (if \>22 mmHg, adjust following pachymetry).
Exclusion criteria
* Have known hypersensitivity to bromfenac or Nepafenac or to any component of the test article (including procedural medications such as anesthetic and/or fluorescein drops, dilating drops, etc.). * Have a known hypersensitivity to salicylates (i.e., aspirin) or to other non steroidal anti inflammatory drugs (NSAIDs). * Have intraocular inflammation (i.e., cells or flare in the anterior chamber as measured on slit lamp examination) in the study eye at the screening visit. * Have a known blood dyscrasia or bone marrow suppression, a diagnosis of uncontrolled/unstable peptic ulcer disease, inflammatory bowel disease, or ulcerative colitis, or any uncontrolled/unstable pulmonary, cardiac, vascular, autoimmune, hepatic, renal, or central nervous system disease. * Have used ocular, topical, or systemic NSAIDs or ocular, topical, or systemic gentamicin, or cyclosporine ophthalmic emulsion within 7 days prior to initiation of dosing with the test article or throughout the duration of the study. * Have used any ocular prostaglandins within 30 days prior to initiation of dosing with the test article or throughout the duration of the study. * Have active corneal pathology noted in the study eye at the screening visit. Active corneal pathology is defined as corneal pathology that is non stable, or greater than mild, or will compromise assessment of the safety or efficacy of treatment. Superficial punctate keratitis in the study eye is a criterion for exclusion. * Have used topical, ocular, inhaled or systemic steroids within 14 days prior to screening. * Have had radial keratotomy, corneal transplant, or corneal refractive surgery in the study eye within the last two years. * Are pregnant or nursing/lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities | Week 6 | ETDRs visual acuities measured at week 6 following uncomplicated phacoemulsification (phaco). ETDRS charts are a standardized eye chart for visual acuity testing accepted by the National Eye Institute and the Food and Drug Administration. The scale is 30-90 letters with higher numbers signifying improved visual acuities. |
| Summed Ocular Inflammation Score (SOIS) | Week 6 | An assessment of the cells and flare, signs of inflammation in ocular tissue. SOIS (summed ocular inflammation) = cells in the anterior chamber/1mmx1mm high powered field+flare/1mmx1mm high powered field. The score of the number of cells in the anterior chamber per 1mmx1mm high powered field ranges from 0-4: 0=no cells, 1=1-5 cell, 2=6-15 cells, 3=16-30 cells, 4\>=30 cells.Flare scores range from 0-3:(0=none, 1=mild, 2=moderate, 3=severe). Cell+flare are added together (cell score + flare score=SOIS score) for a SOIS score (minimum score=0 and maximal score of 7). Higher numbers would indicate more inflammation.The SOIS scale could range from 0-7 with 0 indicating no cells, no flare and 7 reflecting maximal cell 4(\>30 cell/high powered field +3 (severe flare). |
| OCT Retinal Thickness | Week 6 | Stratus OCT scan retinal thickness/volume tabular output report. An experienced ophthalmic technician obtained two scan patterns. The first was the fast macular thickness using 6 radial line scans through a common central axis (fovea) with a retinal thickness/volume tabular output and a retinal-thickness output report. Central retinal thickness was defined as the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris in the central 1 mm area of the minimum 7 mm posterior pole scan. All scans were reviewed by the principal investigator for quality of foveal centration and signal strength. Macular volume is an objective indicator of macualr swelling and can illustrate the amount of inflammation following surgery. Only the study eye was assessed. |
| Macular Volume | 6 weeks | Stratus OCT by experienced technician. Reviewed by principal investigator for quality of foveal centration and signal strength |
Participant flow
Recruitment details
Clinical outcomes of bromfenac ophthalmic solution 0.09% QD and nepafenac 0.1% ophthalmic suspension TID post cataract surgery with posterior chamber intraocular lens implantation, specifically looking at any differences in Early Treatment Diabetic Retinopathy Study visual acuities, macular volume, and/or retinal thickness changes.
Pre-assignment details
Subjects were randomized to receive bromfenac(n=12) QD or nepafenac(n=11) TID. Dosing was 3 days before cataract surgery through day 21 postop. Subjects could not have used ocular/topical, systemic NSAIDs, gentamicin, or cyclosporine ophthalmic emulsion 7 days or prostaglandins 30 days prior to initial dosing of test article or during the study.
Participants by arm
| Arm | Count |
|---|---|
| Bromday Bromfenac : bromfenac 0.9% QD starting 3 days prior to cataract surgery, on the day of surgery and for up to 45 days after surgery | 12 |
| Nevanac Nepafenac : nepafenac ophthalmic suspension 0.1% TID dosed 3 days prior to cataract surgery, on the day of surgery, and for up to 45 days after surgery | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | advanced psc cataract outlier | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Nevanac | Bromday | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 11 Participants | 21 Participants |
| Age, Continuous | 69.7 years STANDARD_DEVIATION 9 | 70.1 years STANDARD_DEVIATION 10.5 | 69.9 years STANDARD_DEVIATION 9.5 |
| Region of Enrollment United States | 11 participants | 12 participants | 23 participants |
| Sex: Female, Male Female | 6 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 1 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities
ETDRs visual acuities measured at week 6 following uncomplicated phacoemulsification (phaco). ETDRS charts are a standardized eye chart for visual acuity testing accepted by the National Eye Institute and the Food and Drug Administration. The scale is 30-90 letters with higher numbers signifying improved visual acuities.
Time frame: Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bromday | Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities | 51.3 letters | Standard Deviation 6.818 |
| Nevanac | Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuities | 52 letters | Standard Deviation 6.75 |
Primary
Macular Volume
Stratus OCT by experienced technician. Reviewed by principal investigator for quality of foveal centration and signal strength
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bromday | Macular Volume | 0.1815 mm cubed | Standard Deviation 0.49 |
| Nevanac | Macular Volume | 0.1765 mm cubed | Standard Deviation 0.34 |
Primary
OCT Retinal Thickness
Stratus OCT scan retinal thickness/volume tabular output report. An experienced ophthalmic technician obtained two scan patterns. The first was the fast macular thickness using 6 radial line scans through a common central axis (fovea) with a retinal thickness/volume tabular output and a retinal-thickness output report. Central retinal thickness was defined as the distance between the inner limiting membrane of the retina and the inner border of the choriocapillaris in the central 1 mm area of the minimum 7 mm posterior pole scan. All scans were reviewed by the principal investigator for quality of foveal centration and signal strength. Macular volume is an objective indicator of macualr swelling and can illustrate the amount of inflammation following surgery. Only the study eye was assessed.
Time frame: Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bromday | OCT Retinal Thickness | 230.7 micrometers cubed | Standard Deviation 30.63 |
| Nevanac | OCT Retinal Thickness | 223.8 micrometers cubed | Standard Deviation 25.36 |
Primary
Summed Ocular Inflammation Score (SOIS)
An assessment of the cells and flare, signs of inflammation in ocular tissue. SOIS (summed ocular inflammation) = cells in the anterior chamber/1mmx1mm high powered field+flare/1mmx1mm high powered field. The score of the number of cells in the anterior chamber per 1mmx1mm high powered field ranges from 0-4: 0=no cells, 1=1-5 cell, 2=6-15 cells, 3=16-30 cells, 4\>=30 cells.Flare scores range from 0-3:(0=none, 1=mild, 2=moderate, 3=severe). Cell+flare are added together (cell score + flare score=SOIS score) for a SOIS score (minimum score=0 and maximal score of 7). Higher numbers would indicate more inflammation.The SOIS scale could range from 0-7 with 0 indicating no cells, no flare and 7 reflecting maximal cell 4(\>30 cell/high powered field +3 (severe flare).
Time frame: Week 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Bromday | Summed Ocular Inflammation Score (SOIS) | 0.15 units on a scale | Standard Deviation 0.229 |
| Nevanac | Summed Ocular Inflammation Score (SOIS) | 0.2 units on a scale | Standard Deviation 0.245 |