Comparison of Two Steroid Regimens to Prevent Transplant Rejection After Corneal Transplant (DMEK)

• Sponsor: Price Vision Group (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01448213
• Collaborator: (none)
• Enrollment: 264
• Locations: 2
• Arms: 2
• Duration (Months): 27
• Patients Per Site: 132
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare two different commonly used steroid dosing regimens after Descemet's membrane endothelial keratoplasty (DMEK) transplant surgery. The investigators hope to determine if one is more effective at preventing rejection or if both are equally effective.

Condition or Disease	Intervention/Treatment	Phase
Fuchs' Dystrophy; Bullous Keratopathy	Drug: Prednisolone acetate; Drug: Fluorometholone	Phase 2

Detailed Description

Graft rejection is one of the leading causes of cornea transplant failure. To help prevent rejection, corticosteroid eye drops are used after transplant surgery. The steroid eye drop dosing regimen varies from surgeon to surgeon, because no studies have been done to determine the optimum dosing regimen.

Study Design

• Study Type: Interventional
• Actual Enrollment: 264 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Prevention
• Official Title: Comparison Of Two Corticosteroid Dosing Regimens For Prevention Of Corneal Transplant Rejection Episodes After Descemet's Membrane Endothelial Keratoplasty
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fluorometholone 0.1% Solution Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.	Drug: Fluorometholone; Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.
Active Comparator: Prednisolone acetate 1% Solution Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.	Drug: Prednisolone acetate; Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.

Outcome Measures

Primary Outcome Measures

1. Number of Eyes With Immunologic Graft Rejection Episodes [Within 1 year]

Secondary Outcome Measures

1. Number of Eyes With Intraocular Pressure (IOP) Elevation [one day, two days, one week, one month, 3 months, 6 months and 12 months after DMEK]

   Absolute IOP greater than or equal to 24 mm Hg or a relative increase of 10 mm Hg over the baseline preoperative reading.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA: The following are requirements for inclusion in the study:

• Male or female patient, at least 18 years of age, who is a candidate for DMEK due to corneal endothelial dysfunction or who has undergone DMEK within the last 7 weeks

• Patient is able and willing to administer eye drops.

• Patient is able to comprehend and has signed the Informed Consent form.

• Patient is likely to complete the entire one-year course of the study.

• Patient has best corrected visual acuity (BCVA) of at least 20/200 in the fellow eye.

• Corneal neovascularization will not be judged as an exclusion criteria for the study

EXCLUSION CRITERIA: The following are exclusion criteria for patients in this study:

• A patient with a previous failed graft in the study eye with a history of a prior rejection episode

• A patient exhibiting any intraocular inflammation

• A patient with a known sensitivity to any of the ingredients in the study medications

• A patient who has a condition (i.e., UNCONTROLLED systemic disease) or is in a situation which in the investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study

• A patient with abnormal eyelid function

• A patient that is exhibiting active corneal ulceration, keratitis, or conjunctivitis, or who has a history of herpetic keratitis

• A patient with the presence of any ocular disease that would interfere with the evaluation of the study treatment

• A patient with a history of non-compliance with using prescribed medication

• A patient who is concurrently involved in or participated in another clinical trial within 30 days prior to enrollment in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Price Vision Group	Indianapolis	Indiana	United States	46260
2	University of Erlangen	Erlangen		Germany

Sponsors and Collaborators

• Price Vision Group

Investigators

• Principal Investigator: Francis W Price, MD, Price Vision Group
• Principal Investigator: Friedrich Kruse, MD, University of Erlangen, Germany

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Price Vision Group Website

Publications

None provided.

• Responsible Party: Price Vision Group
• ClinicalTrials.gov Identifier: NCT01448213
• Other Study ID Numbers: 2011-0329
• First Posted: Oct 7, 2011
• Last Update Posted: Sep 3, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Price Vision Group: DMEK; Rejection; Corticosteroid
• Additional relevant MeSH terms: Fuchs' Endothelial Dystrophy; Fluorometholone; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Study Results

Participant Flow

Arm/Group Title	Fluorometholone 0.1% Solution	Prednisolone Acetate 1% Solution
Arm/Group Description	Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study. Fluorometholone: Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.	Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study. Prednisolone acetate: Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.
Period Title: Overall Study
STARTED	130	134
COMPLETED	113	112
NOT COMPLETED	17	22

Baseline Characteristics

Arm/Group Title	Fluorometholone 0.1% Solution	Prednisolone Acetate 1% Solution	Total
Arm/Group Description	Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study. Fluorometholone: Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.	Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study. Prednisolone acetate: Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.	Total of all reporting groups
Overall Participants	161	164	325
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69	67	68
Sex: Female, Male (Count of Participants)
Female	107 66.5%	105 64%	212 65.2%
Male	54 33.5%	59 36%	113 34.8%

Outcome Measures

1. Primary Outcome

Title	Number of Eyes With Immunologic Graft Rejection Episodes
Time Frame	Within 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluorometholone 0.1% Solution	Prednisolone Acetate 1% Solution
Arm/Group Description	Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study. Fluorometholone: Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.	Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study. Prednisolone acetate: Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.
Measure Participants	130	134
Measure Number of Eyes	161	164
Number [eyes]	2	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluorometholone 0.1% Solution, Prednisolone Acetate 1% Solution
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	Number of Eyes With Intraocular Pressure (IOP) Elevation
Description	Absolute IOP greater than or equal to 24 mm Hg or a relative increase of 10 mm Hg over the baseline preoperative reading.
Time Frame	one day, two days, one week, one month, 3 months, 6 months and 12 months after DMEK

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluorometholone 0.1% Solution	Prednisolone Acetate 1% Solution
Arm/Group Description	Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study. Fluorometholone: Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.	Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study. Prednisolone acetate: Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.
Measure Participants	130	134
Measure eyes	161	164
Number [eyes]	9	32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fluorometholone 0.1% Solution, Prednisolone Acetate 1% Solution
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Log Rank
	Comments

Adverse Events

Arm/Group Title	Fluorometholone 0.1% Solution		Prednisolone Acetate 1% Solution
Arm/Group Description	Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study. Fluorometholone: Subjects assigned to Treatment Regimen B will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for one month. Then they will instill one drop of fluorometholone four times a day in the transplant eye for 2 months, then 3 times a day for 1 month, then twice a day for 1 month, then once a day until the subject exits the study.		Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study. Prednisolone acetate: Subjects assigned to Treatment Regimen A will instill 1 drop of prednisolone acetate 1% four times a day in the transplant eye for 3 months, then 3 times a day for one month, then twice a day for one month, then once a day until the subject exits the study.
All Cause Mortality
	Fluorometholone 0.1% Solution		Prednisolone Acetate 1% Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluorometholone 0.1% Solution		Prednisolone Acetate 1% Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/130 (0%)		0/134 (0%)
Other (Not Including Serious) Adverse Events
	Fluorometholone 0.1% Solution		Prednisolone Acetate 1% Solution
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/130 (0%)		13/134 (9.7%)
Eye disorders
Intraocular pressure control problem requiring discontinuation of study drug	0/130 (0%)	0	13/134 (9.7%)	13

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.