Loteprednol vs. Prednisolone and Fluorometholone

• Sponsor: University of Utah (Other)
• Overall Status: Completed
• CT.gov ID: NCT03123614
• Collaborator: (none)
• Enrollment: 131
• Location: 1
• Arms: 2
• Actual Duration (Months): 45.4
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

Corneal haze, in which the cornea becomes cloudy, is a well-known and a potentially vision-threatening postoperative complication of photorefractive keratectomy (PRK). Topical ophthalmic corticosteroids are routinely prescribed by most surgeons postoperatively to help prevent this complication.

Goals of topical steroids use after PRK include effective modulation of the healing response to prevent corneal haze while at the same time minimizing side effects, such as intraocular pressure elevation or cataract formation. Loteprednol etabonate is a corticosteroid that exerts its therapeutic effects and is then quickly changed into inactive metabolites. This relatively fast metabolism of loteprednol gives it a lower side effect profile than other steroids, including a smaller effect on intraocular pressure. In the ophthalmic literature, there is currently no consensus on a standard regimen or which type of corticosteroid should be used after PRK.

Investigators are conducting a prospective, randomized trial to compare the incidence of intraocular pressure rise and visually significant postoperative corneal haze after PRK with the use of loteprednol 0.5% gel compared to the use of earlier generation steroids, prednisolone acetate 1% suspension and fluorometholone 0.1% suspension.

Condition or Disease	Intervention/Treatment	Phase
Intraocular Pressure; Corneal Opacity	Drug: Loteprednol Etabonate 0.5% Oph Gel; Drug: Prednisolone Acetate 1% Oph Susp	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Examiners are masked to the treatment arm when obtaining measurements of intraocular pressure (IOP) and grading corneal haze.
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Loteprednol 0.5% Gel for Routine Prophylaxis After Photorefractive Keratectomy Compared to Prednisolone Acetate 1% Suspension and Fluorometholone 0.1% Suspension
• Actual Study Start Date: Sep 19, 2014
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Loteprednol Etabonate 0.5% Oph Gel Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response.	Drug: Loteprednol Etabonate 0.5% Oph Gel
Active Comparator: Prednisolone acetate 1% Oph Susp Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response.	Drug: Prednisolone Acetate 1% Oph Susp

Outcome Measures

Primary Outcome Measures

1. Change in Intraocular Pressure (IOP) From Baseline Through Month 3 [Baseline, 1 week post-op, 1 month post-op, 2 months post-op, 3 months post-op]

   Intraocular pressure will be measured by applanation tonometry

Secondary Outcome Measures

1. Number of Eyes With Corneal Haze [12 months]

   As determined by slit lamp examination

2. Uncorrected Visual Acuity [3 months]

   Best uncorrected visual acuity will be measured at 3 months

3. Best Corrected Visual Acuity at 3 Months [3 months]

   Best uncorrected visual acuity will be measured at 3 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All subjects who are deemed suitable candidates for PRK after routine refractive surgery screening will be considered eligible for participation in this study.

• Subjects must be at least 21 years of age and not pregnant or nursing (due to fluctuations in visual parameters during pregnancy).

Exclusion Criteria:

• Selection will be consistent with the current standard of care for PRK. Any patient that is not a suitable candidate for PRK will not be included.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moran Eye Center - Midvalley Location	Murray	Utah	United States	84107

Sponsors and Collaborators

• University of Utah

Investigators

• Principal Investigator: Mark Mifflin, MD, University of Utah Moran Eye Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 27, 2018

More Information

Publications

None provided.

• Responsible Party: Mark Mifflin, Professor, Ophthalmology/Visual Sciences, University of Utah
• ClinicalTrials.gov Identifier: NCT03123614
• Other Study ID Numbers: IRB # 75978
• First Posted: Apr 21, 2017
• Last Update Posted: May 26, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Mark Mifflin, Professor, Ophthalmology/Visual Sciences, University of Utah: Photorefractive keratectomy
• Additional relevant MeSH terms: Corneal Opacity; Loteprednol Etabonate; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
Period Title: Overall Study
STARTED	57	74
COMPLETED	57	74
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp	Total
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp	Total of all reporting groups
Overall Participants	57	74	131
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	57 100%	74 100%	131 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.6 (8.8)	35.3 (6.2)	35.0 (7.3)
Sex: Female, Male (Count of Participants)
Female	24 42.1%	36 48.6%	60 45.8%
Male	33 57.9%	38 51.4%	71 54.2%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	57 100%	74 100%	131 100%
Intraocular Pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	14.38 (2.11)	14.30 (2.13)	14.34 (2.12)

Outcome Measures

1. Primary Outcome

Title	Change in Intraocular Pressure (IOP) From Baseline Through Month 3
Description	Intraocular pressure will be measured by applanation tonometry
Time Frame	Baseline, 1 week post-op, 1 month post-op, 2 months post-op, 3 months post-op

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
Measure Participants	57	74
Baseline intraocular pressure (IOP)	14.38 (2.11)	14.30 (2.13)
IOP 1 week postop	13.67 (2.34)	13.28 (3.37)
IOP 1 month postop	14.15 (2.88)	14.60 (4.20)
IOP 2 months postop	13.36 (2.53)	13.16 (2.80)
IOP 3 months postop	13.15 (2.43)	12.22 (2.38)

2. Secondary Outcome

Title	Number of Eyes With Corneal Haze
Description	As determined by slit lamp examination
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
Measure Participants	57	74
Measure Eyes	114	147
Count of Units [Eyes]	3	7

3. Secondary Outcome

Title	Uncorrected Visual Acuity
Description	Best uncorrected visual acuity will be measured at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
Measure Participants	57	74
Mean (Standard Deviation) [logMAR]	-0.078 (0.10)	-0.075 (0.09)

4. Secondary Outcome

Title	Best Corrected Visual Acuity at 3 Months
Description	Best uncorrected visual acuity will be measured at 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel	Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel	Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
Measure Participants	57	74
Mean (Standard Deviation) [logMAR]	-0.120 (0.059)	-0.114 (0.03)

Adverse Events

Time Frame	3 years and 10 months
Arm/Group Title	Loteprednol Etabonate 0.5% Oph Gel		Prednisolone Acetate 1% Oph Susp
Arm/Group Description	Group 1 will use loteprednol 0.5% gel in both eyes, starting at a frequency of four times per day for the first week and then tapered off based on clinical judgement of the corneal healing response. Loteprednol Etabonate 0.5% Oph Gel		Group 2 will use prednisolone acetate 1% suspension in both eyes, starting at a frequency of four times per day for the first week, then tapered down to a regimen of fluorometholone 0.1% suspension, which will then be tapered off based on clinical judgement of the corneal healing response. Prednisolone Acetate 1% Oph Susp
All Cause Mortality
	Loteprednol Etabonate 0.5% Oph Gel		Prednisolone Acetate 1% Oph Susp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/74 (0%)
Serious Adverse Events
	Loteprednol Etabonate 0.5% Oph Gel		Prednisolone Acetate 1% Oph Susp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/74 (0%)
Other (Not Including Serious) Adverse Events
	Loteprednol Etabonate 0.5% Oph Gel		Prednisolone Acetate 1% Oph Susp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/57 (5.3%)		7/74 (9.5%)
Eye disorders
Non-visually significant corneal haze	3/57 (5.3%)	3	7/74 (9.5%)	7

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.