Trial of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation

• Sponsor: Cornea Research Foundation of America (Other)
• Overall Status: Completed
• CT.gov ID: NCT03248037
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.1
• Patients Per Site Per Month: 5.4

Study Details

Study Description

Brief Summary

Cornea transplant recipients who are using topical corticosteroids long-term to prevent transplant rejection will be randomized to use netarsudil or placebo.

Condition or Disease	Intervention/Treatment	Phase
Fuchs' Endothelial Dystrophy; Bullous Keratopathy	Drug: Netarsudil; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Randomized, Double-masked, Placebo-controlled Evaluation of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation
• Actual Study Start Date: Sep 5, 2017
• Actual Primary Completion Date: Jul 9, 2019
• Actual Study Completion Date: Jul 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Netarsudil Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months	Drug: Netarsudil; netarsudil opthalmic solution 0.02%
Placebo Comparator: Placebo Placebo eye drop, dosed topically once a day for 9 months	Drug: Placebo; Placebo eye drops

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure [from date of randomization until the date of first documented intraocular pressure elevation exceeding defined threshold up to 9 months]

   Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• At least 18 years of age; male or female patient undergoing Descemet membrane endothelial keratoplasty; 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 nine-month course of the study.

Exclusion Criteria:

• A patient exhibiting pre-operative 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 who has been diagnosed with uncontrolled glaucoma, prior aqueous shunt or trabeculectomy, or with preoperative intraocular pressure > 22 mm Hg in the potential study eye; presence of any ocular disease that would interfere with the evaluation of the study treatment (however, patients with a history of cystoid macular edema, age-related macular degeneration, corneal neovascularization, and other non-interfering comorbidities may be enrolled); a patient with a history of non-compliance with using prescribed medication; a patient who is concurrently involved in or participated in another randomized clinical trial within 30 days prior to enrollment in this study; patients who are pregnant or planning to become pregnant within the duration of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Price Vision Group	Indianapolis	Indiana	United States	46260

Sponsors and Collaborators

• Cornea Research Foundation of America

Investigators

• Principal Investigator: Francis W Price, Jr, MD, Price Vision Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 23, 2017

More Information

Publications

• Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22. Review.
• Vajaranant TS, Price MO, Price FW, Gao W, Wilensky JT, Edward DP. Visual acuity and intraocular pressure after Descemet's stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. Ophthalmology. 2009 Sep;116(9):1644-50. doi: 10.1016/j.ophtha.2009.05.034. Epub 2009 Jul 29.

• Responsible Party: Cornea Research Foundation of America
• ClinicalTrials.gov Identifier: NCT03248037
• Other Study ID Numbers: 2017-003
• First Posted: Aug 14, 2017
• Last Update Posted: Feb 12, 2021
• Last Verified: Jan 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
• Additional relevant MeSH terms: Fuchs' Endothelial Dystrophy

Study Results

Participant Flow

Recruitment Details	As specified in the protocol, a total of 120 unique participants were enrolled in the study; 71 enrolled both eyes in the study and the fellow eyes were automatically assigned to opposite treatment arms, so 71 subjects participated in both treatment arms.

Arm/Group Title	Netarsudil	Placebo
Arm/Group Description	Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months Netarsudil: netarsudil opthalmic solution 0.02%	Placebo eye drop, dosed topically once a day for 9 months Placebo: Placebo eye drops
Period Title: Overall Study
STARTED	95	96
COMPLETED	74	87
NOT COMPLETED	21	9

Baseline Characteristics

Arm/Group Title	Netarsudil	Placebo	Total
Arm/Group Description	Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months Netarsudil: netarsudil opthalmic solution 0.02%	Placebo eye drop, dosed topically once a day for 9 months Placebo: Placebo eye drops	Total of all reporting groups
Overall Participants	95	96	191
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68	67	67
Sex: Female, Male (Count of Participants)
Female	54 56.8%	61 63.5%	115 60.2%
Male	41 43.2%	35 36.5%	76 39.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	95 100%	96 100%	191 100%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure
Description	Intraocular pressure measurement exceeding 24 mm Hg or more than 10 mm Hg greater than the pre-randomization reading.
Time Frame	from date of randomization until the date of first documented intraocular pressure elevation exceeding defined threshold up to 9 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Netarsudil	Placebo
Arm/Group Description	Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months Netarsudil: netarsudil opthalmic solution 0.02%	Placebo eye drop, dosed topically once a day for 9 months Placebo: Placebo eye drops
Measure Participants	95	96
Count of Participants [Participants]	11 11.6%	18 18.8%

Adverse Events

Time Frame	9 months
Arm/Group Title	Netarsudil		Placebo
Arm/Group Description	Netarsudil ophthalmic solution 0.02%, dosed topically once a day for 9 months Netarsudil: netarsudil opthalmic solution 0.02%		Placebo eye drop, dosed topically once a day for 9 months Placebo: Placebo eye drops
All Cause Mortality
	Netarsudil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/96 (0%)
Serious Adverse Events
	Netarsudil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/95 (0%)		0/96 (0%)
Other (Not Including Serious) Adverse Events
	Netarsudil		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/95 (32.6%)		18/96 (18.8%)
Eye disorders
Air re-injection	20/95 (21.1%)	20	18/96 (18.8%)	18
Ocular irritation considered related to study drug use	22/95 (23.2%)	22	0/96 (0%)	0

Limitations/Caveats

[Not Specified]

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.