Effect of Nepafenac on Post-operative Macular Swelling Following Uncomplicated Cataract Surgery

• Sponsor: University of North Carolina, Chapel Hill (Other)
• Overall Status: Completed
• CT.gov ID: NCT00494494
• Collaborator: Research to Prevent Blindness (Other)
• Enrollment: 82
• Location: 1
• Arms: 2
• Duration (Months): 10
• Patients Per Site Per Month: 8.2

Study Details

Study Description

Brief Summary

Purpose: Study the effect of nepafenac ophthalmic suspension 0.1% to prevent post-operative cystoid macular edema following uncomplicated cataract surgery

Participants: Patients having cataract surgery at UNC who meet eligibility criteria

Procedures (methods): Patients will have pre and post-operative vision measured and optical coherence tomography (OCT) testing, also cataract density and intraoperative phacoemulsification parameters including ultrasound power and ultrasound time will be measured. Patients will be randomized into two groups. Group 1 will be treated with standard post-operative cataract management. Group 2 will be treated with standard post-operative cataract management plus topical nepafenac for one month. Post-operative macular thickness will be studied by analyzing the visual acuity and OCT measurements at two months post surgery.

Condition or Disease	Intervention/Treatment	Phase
Cystoid Macular Edema	Drug: Standard Care; Drug: nepafenac	Phase 4

Detailed Description

We plan to enroll 80 patients in this prospective randomized clinical trial. Eligible patients will be randomized into two groups. All patients will have pre-operative Early Treatment of Diabetic Retinopathy Study (ETDRS) vision measured and pre-operative OCT (Humphrey-Zeiss Medical Systems, San Leandro, CA) in both eyes. OCT measurements will include total macular volume, central foveal thickness, and average macular thickness. Pre-operatively, all cataracts will be graded using the LOCS III classification system.10 Group 1 will receive pre-operative topical nepafenac to maintain intra-operative pupillary dilation which is standard care for cataract surgery. Following surgery Group 1 will be treated with standard post operative cataract treatment, including a topical antibiotic and a topical corticosteroid. Group 2 will also receive pre-operative topical nepafenac to maintain intra-operative pupillary dilation. Following surgery patients in Group 2 will be treated with topical nepafenac, a topical antibiotic, and a topical corticosteroid. Group 2 will be given the 3ml bottle of nepafenac to take home and instructed to use it three times per day for one month. Intra-operative surgical parameters including ultrasound time and average percent phacoemulsification power will be recorded for all surgeries. All patients will be seen on post-operative day one, one week, one month, and two months. At the two month visit, best corrected ETDRS vision and OCT will be repeated in both eyes. The two month visual acuity and post-operative OCT will be analyzed to evaluate the effect of nepafenac on CME following cataract surgery. Wilcoxon signed rank test will be used to compare pre-operative and post-operative differences between visual acuity and OCT measurements. The Spearman correlation will be used to compare the variables in the study including cataract density, ultrasound time, average percent phacoemulsification power, and OCT measurements.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Effect of Nepafenac on Post-operative Cystoid Macular Edema Following Uncomplicated Cataract Surgery
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard Treatment topical antibiotic for 10 days and a topical corticosteroid for 1 month	Drug: Standard Care; topical antibiotic for 10 days plus topical corticosteroids for 1 month
Experimental: Nepafenac 1 drop per study eye three times per day for 30 days in addition to standard care	Drug: nepafenac; liquid drops, administered three times per day for 1 month in addition to standard care use of topical antibiotic and topical corticosteroid

Outcome Measures

Primary Outcome Measures

1. Central Macular Thickness (Difference in Mean Pre-post Changes by the Two Treatment Groups) [baseline and 8 weeks]

   The endpoints of the study were change in macular thickness measured by OCT in the central 1mm diameter centred on the fovea (central macular thickness)

2. Pre-operative Best Corrected Visual Acuity (BCVA) [baseline]

   Patients were instructed to read letters on the EDTRS visual acuity chart. The mean and standard deviation for each group was measured. Letters range from 0 (20/2000) to 110 (20/12.5), with the higher number signaling better visual acuity.

3. Foveal Thickness [baseline and 8 weeks]

   difference in mean pre-post changes by the two treatment groups

4. Macular Volume (Difference in Mean Pre-post Changes by the Two Treatment Groups) [baseline and 8 weeks]

5. Post-operative Best Corrected Visual Acuity (BCVA) [baseline and 8 weeks]

   The patients were again instructed to read letters on the ETDRS chart 8 weeks post-surgery. The mean and standard deviation for each group was recorded. Letters range from 0 (20/2000) to 110 (20/12.5), with the higher number signaling better visual acuity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• over age 50

• having cataract surgery at UNC

Exclusion Criteria:

• medically controlled diabetes

• history of intraocular surgery

• abnormal pre-op optical coherence tomography scan

• history of ocular inflammation

• have age related macular degeneration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27517

Sponsors and Collaborators

• University of North Carolina, Chapel Hill
• Research to Prevent Blindness

Investigators

• Principal Investigator: Kenneth C Cohen, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00494494
• Other Study ID Numbers: 05-3115
• First Posted: Jun 29, 2007
• Last Update Posted: Jul 12, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: cystoid macular edema; cataract; nonsteroidal antiinflammatory drugs; optical coherence tomography
• Additional relevant MeSH terms: Cataract; Macular Edema; Edema; Nepafenac

Study Results

Participant Flow

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Period Title: Overall Study
STARTED	40	39
COMPLETED	40	39
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard Treatment	Nepafenac	Total
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care	Total of all reporting groups
Overall Participants	40	39	79
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	40 100%	39 100%	79 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.33 (8.04)	73.95 (8.99)	72.14 (8.52)
Sex: Female, Male (Count of Participants)
Female	19 47.5%	18 46.2%	37 46.8%
Male	21 52.5%	21 53.8%	42 53.2%
Region of Enrollment (participants) [Number]
United States	40 100%	39 100%	79 100%

Outcome Measures

1. Primary Outcome

Title	Central Macular Thickness (Difference in Mean Pre-post Changes by the Two Treatment Groups)
Description	The endpoints of the study were change in macular thickness measured by OCT in the central 1mm diameter centred on the fovea (central macular thickness)
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

Three subjects in the treatment group and two subjects in the control group had unreliable preoperative OCT scans because of dense posterior subcapsular cataracts. These subjects were excluded from the analysis.

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Measure Participants	40	39
Mean (95% Confidence Interval) [microns]	2.78	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment, Nepafenac
	Comments	The null hypothesis is that there is no correlation between the 2 groups. Standard methods were used for power calculation to determine the sample size needed to have 0.90 power for the comparison between two groups at the two-sided significance of 0.05.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Our estimate of a clinically relevant increase is 25 microns. With these specifications, the sample size that is required to have 0.90 power for the comparison between two groups at the two-sided 0.05 significance level is about 10 per group.
Statistical Test of Hypothesis	p-Value	0.7029
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.82
	Confidence Interval	(2-Sided) 95%; -3.27 to 8.91
	Parameter Dispersion	Type: Standard Deviation; Value: 13.8
	Estimation Comments

2. Primary Outcome

Title	Pre-operative Best Corrected Visual Acuity (BCVA)
Description	Patients were instructed to read letters on the EDTRS visual acuity chart. The mean and standard deviation for each group was measured. Letters range from 0 (20/2000) to 110 (20/12.5), with the higher number signaling better visual acuity.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

The analysis was per protocol. At baseline, everybody was given a Best Corrected Visual Acuity Assessment (BCVA).

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Measure Participants	40	39
Mean (Standard Deviation) [letters]	38.48 (9.83)	40.49 (9.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment, Nepafenac
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1937
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.01
	Confidence Interval	(2-Sided) 95%; -2.41 to 6.43
	Parameter Dispersion	Type: Standard Deviation; Value: 9.56
	Estimation Comments

3. Primary Outcome

Title	Foveal Thickness
Description	difference in mean pre-post changes by the two treatment groups
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Measure Participants	40	39
Mean (95% Confidence Interval) [microns]	-2.0	4.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment, Nepafenac
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5066
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	6.70
	Confidence Interval	(2-Sided) 95%; -3.12 to 16.52
	Parameter Dispersion	Type: Standard Deviation; Value: 19.6
	Estimation Comments

4. Primary Outcome

Title	Macular Volume (Difference in Mean Pre-post Changes by the Two Treatment Groups)
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Measure Participants	40	39
Mean (95% Confidence Interval) [microns]	0.05	0.10

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment, Nepafenac
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5099
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.227
	Parameter Dispersion	Type: Standard Deviation; Value: 0.21
	Estimation Comments

5. Primary Outcome

Title	Post-operative Best Corrected Visual Acuity (BCVA)
Description	The patients were again instructed to read letters on the ETDRS chart 8 weeks post-surgery. The mean and standard deviation for each group was recorded. Letters range from 0 (20/2000) to 110 (20/12.5), with the higher number signaling better visual acuity.
Time Frame	baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Treatment	Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.	1 drop per study eye three times per day for 30 days plus standard care
Measure Participants	40	39
Mean (95% Confidence Interval) [letters]	54.46	55.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Treatment, Nepafenac
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5005
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; -1.49 to 3.55
	Parameter Dispersion	Type: Standard Deviation; Value: 5.64
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Serious and/or other adverse Events were not collected for this study.
Arm/Group Title	Standard Treatment		Nepafenac
Arm/Group Description	These subjects only received the standard of care for post-operative cataract, which consists of a topical antibiotic and a topical corticosteroid.		1 drop per study eye three times per day for 30 days plus standard care
All Cause Mortality
	Standard Treatment		Nepafenac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Treatment		Nepafenac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Standard Treatment		Nepafenac
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Although the peak incidence of CME is said to be at 4-12 weeks after surgery, we may have missed the time course for detecting the maximum increased OCT measured macular thickness.

More Information

Certain Agreements

All Principal Investigators ARE 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.