Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Retinal Detachment

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ClinicalTrials.gov Identifier: NCT06033703

Recruitment Status : Not yet recruiting

First Posted : September 13, 2023

Last Update Posted : January 10, 2024

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Sponsor:

Information provided by (Responsible Party):

Leo Am Kim, M.D., Massachusetts Eye and Ear Infirmary

Study Description

Brief Summary:

This study has two main objectives. The first objective is to study the pharmacokinetics of topical netarsudil administration in the posterior segment of the eye, where netarsudil must exert its effect in order to prevent formation of tractional membranes.

The second objective is to assess the safety profile of topical netarsudil in the pre- and post-operative periods. A secondary objective of the study is to begin to assess signs of efficacy in preventing formation of tractional membranes post-operatively.

Condition or disease	Intervention/treatment	Phase
Rhegmatogenous Retinal Detachment Proliferative Vitreoretinopathy	Drug: Netarsudil Ophthalmic	Phase 1 Phase 2

Detailed Description:

This is an open-label, randomized study that will test the safety and pharmacokinetics of topical netarsudil at a dose frequency of once-daily in two cohorts of patients: those with primary rhegmatogenous detachments, and those with established proliferative vitreoretinopathy. The intervention will be topical application of Netarsudil from time of diagnosis of retinal detachment to 16 weeks post-operatively.

Patients will be randomized to one of the following groups:

The primary rhegmatogenous detachment cohort: A total of 24 study subjects (24 eyes) will be stratified by their lens status (12 phakic versus 12 pseudophakic). All patients will receive once per day dosing of netarsudil.
The proliferative vitreoretinopathy cohort: A total of 24 study subjects (24 eyes) will be stratified by their lens status (12 phakic versus 12 pseudophakic). All patients will receive once per day dosing of netarsudil.

After surgery, patients will continue on either once per day dosing of Netarsudil.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	48 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Primary Rhegmatogenous Detachments and Retinal Detachment Due to Proliferative Vitreoretinopathy or Open-Globe Injury: A Phase I/II Clinical Trial
Estimated Study Start Date :	February 2024
Estimated Primary Completion Date :	September 2024
Estimated Study Completion Date :	December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Retinal Detachment

Drug Information available for: Netarsudil Rhopressa

Genetic and Rare Diseases Information Center resources: Vitreoretinal Degeneration Conversion Disorder

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Primary retinal detachment, Phakic group Phakic patients with primary rhegmatogenous retinal detachment repair within 7 days of symptom onset, undergoing vitrectomy or vitrectomy with scleral buckle will be included. Patients will receive topical Netarsudil ophthalmic solution 0.02%: once per day, from time of diagnosis of retinal detachment to 16 weeks post-operatively.	Drug: Netarsudil Ophthalmic Topical administration of Netarsudil Other Name: Rhopressa
Experimental: Primary retinal detachment, Pseudophakic group Pseudophakic patients with primary rhegmatogenous retinal detachment repair within 7 days of symptom onset, undergoing vitrectomy or vitrectomy with scleral buckle will be included. Patients will receive topical Netarsudil ophthalmic solution 0.02%: once per day, from time of diagnosis of retinal detachment to 16 weeks post-operatively.	Drug: Netarsudil Ophthalmic Topical administration of Netarsudil Other Name: Rhopressa
Experimental: Secondary retinal detachment, Phakic group Phakic patients with retinal detachment due with proliferative vitreoretinopathy (grade C or higher) or retinal detachment associated with open globe trauma, undergoing vitrectomy or vitrectomy with scleral buckle will be included. Patients will receive topical Netarsudil ophthalmic solution 0.02%: once per day, from time of diagnosis of retinal detachment to 16 weeks post-operatively.	Drug: Netarsudil Ophthalmic Topical administration of Netarsudil Other Name: Rhopressa
Experimental: Secondary retinal detachment, Pseudophakic group Pseudophakic patients with retinal detachment due with proliferative vitreoretinopathy (grade C or higher) or retinal detachment associated with open globe trauma, undergoing vitrectomy or vitrectomy with scleral buckle will be included. Patients will receive topical Netarsudil ophthalmic solution 0.02%: once per day, from time of diagnosis of retinal detachment to 16 weeks post-operatively.	Drug: Netarsudil Ophthalmic Topical administration of Netarsudil Other Name: Rhopressa

Outcome Measures

Primary Outcome Measures :

The concentration of netarsudil in the vitreous to assess its pharmacokinetic properties. [ Time Frame: Through study completion, an average of 1 year ]
Netarsudil concentration in the posterior segment of the eye, using High-performance liquid chromatography (HPLC)
Serious adverse events [ Time Frame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery ]
Unexpected serious adverse events

Secondary Outcome Measures :

Number of operations within 3 months [ Time Frame: Day 84 after surgery ]
Total number of operation during the first 3 months after surgery
Final attachment status at last follow-up [ Time Frame: Day 168 after surgery ]
Status of the retina (attached versus detached) at last follow-up visit
Visual acuity [ Time Frame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery ]
Best-corrected visual acuity measured using Snellen chart
Spectral domain optical coherence tomography (SD-OCT) of the macula [ Time Frame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery ]
Status of the macula (mac-on versus mac-off)
Adverse events [ Time Frame: Day 1, 7, 28, 56, 84, 126, and 168 after surgery ]
Adverse events including conjunctival injection, subconjunctival hemorrhage, and corneal verticillata, eye irritation, reticular edema of the cornea, hypotony

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

The primary rhegmatogenous detachment cohort will have the following selection criteria:

Inclusion criteria:

Patients > 18 years old
Patients presenting for primary rhegmatogenous retinal detachment repair within 7 days of symptom onset
Patients undergoing vitrectomy or vitrectomy with scleral buckle

Exclusion criteria:

Patient unable to give consent
Patient unable to follow-up
Prior history of retinal detachment incisional surgery in presenting eye
Prior history of open globe injury to presenting eye
Prior history of glaucoma surgery to presenting eye I.e., Status post trabeculectomy, Ahmed tube placement, minimally invasive glaucoma surgery, actively on glaucoma medication
Prior history of corneal disease, or history of corneal edema
Patient already on topical netarsudil in presenting eye
Patient without natural lens or intraocular lens implant (I.e., aphakic patients)
Patients with intraocular pressure <8mm Hg in operative eye
Active or chronic or recurrent uncontrolled ocular or systemic disease
Active or history of chronic or recurrent inflammatory eye disease
Diagnosis of proliferative diabetic retinopathy
Signs of ocular infection at presentation in either eye
Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
Inability to use/ apply topical eye drops

The proliferative vitreoretinopathy cohort will have the following selection criteria:

Inclusion criteria:

Patients > 18 years old
Patient presenting with retinal detachment due with proliferative vitreoretinopathy (grade C or higher) or retinal detachment associated with open globe trauma
Patients undergoing vitrectomy or vitrectomy with scleral buckle

Exclusion criteria:

Patient unable to give consent
Patient unable to follow-up
Prior history of glaucoma surgery to presenting eye I.e., Status post trabeculectomy, Ahmed tube placement, minimally invasive glaucoma surgery
Patient already on topical netarsudil in presenting eye
Patients with intraocular pressure <8mm Hg in operative eye
Active or chronic or recurrent uncontrolled ocular or systemic disease
Active or history of chronic or recurrent inflammatory eye disease
Diagnosis of severe nonproliferative or proliferative diabetic retinopathy or vasoproliferative disease in operative eye
Signs of ocular infection at presentation in either eye
Known or suspected sensitivity or allergy to any of the medications used in the operation or postoperatively
Inability to use/ apply topical eye drops
No Light Perception vision in operative eye
Failure to achieve intraoperative reattachment
Patient with silicone oil instilled in operative eye at time of presentation

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06033703

Contacts

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Contact: Leo Kim, MD, PhD	6175237900	Leo_Kim@meei.harvard.edu
Contact: Center for Clinical Research Operations (CCRO)	6175736060

Sponsors and Collaborators

Massachusetts Eye and Ear Infirmary

Investigators

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Principal Investigator:	Leo Kim, MD, PhD	Massachusetts Eye and Ear

More Information

Publications:

Lin CW, Sherman B, Moore LA, Laethem CL, Lu DW, Pattabiraman PP, Rao PV, deLong MA, Kopczynski CC. Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma. J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):40-51. doi: 10.1089/jop.2017.0023. Epub 2017 Jun 13.

Singh IP, Fechtner RD, Myers JS, Kim T, Usner DW, McKee H, Sheng H, Lewis RA, Heah T, Kopczynski CC. Pooled Efficacy and Safety Profile of Netarsudil Ophthalmic Solution 0.02% in Patients With Open-angle Glaucoma or Ocular Hypertension. J Glaucoma. 2020 Oct;29(10):878-884. doi: 10.1097/IJG.0000000000001634.

Davies E, Jurkunas U, Pineda R 2nd. Pilot Study of Corneal Clearance With the Use of a Rho-Kinase Inhibitor After Descemetorhexis Without Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy. Cornea. 2021 Jul 1;40(7):899-902. doi: 10.1097/ICO.0000000000002691.

Kahook MY, Serle JB, Mah FS, Kim T, Raizman MB, Heah T, Ramirez-Davis N, Kopczynski CC, Usner DW, Novack GD; ROCKET-2 Study Group. Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2). Am J Ophthalmol. 2019 Apr;200:130-137. doi: 10.1016/j.ajo.2019.01.003. Epub 2019 Jan 15.

Serle JB, Katz LJ, McLaurin E, Heah T, Ramirez-Davis N, Usner DW, Novack GD, Kopczynski CC; ROCKET-1 and ROCKET-2 Study Groups. Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2). Am J Ophthalmol. 2018 Feb;186:116-127. doi: 10.1016/j.ajo.2017.11.019. Epub 2017 Dec 1.

Fernandez MM. Reticular Epithelial Edema in Edematous Corneas Treated with Netarsudil. Ophthalmology. 2018 Nov;125(11):1709. doi: 10.1016/j.ophtha.2018.08.004. No abstract available.

Wisely CE, Liu KC, Gupta D, Carlson AN, Asrani SG, Kim T. Reticular Bullous Epithelial Edema in Corneas Treated with Netarsudil: A Case Series. Am J Ophthalmol. 2020 Sep;217:20-26. doi: 10.1016/j.ajo.2020.04.002. Epub 2020 Apr 11.

LoBue SA, Moustafa GA, Vu A, Amin M, Nguyen T, Goyal H. Transient Reticular Cystic Corneal Epithelial Edema With Topical Netarsudil: A Case Series and Review. Cornea. 2021 Aug 1;40(8):1048-1054. doi: 10.1097/ICO.0000000000002621.

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Responsible Party:	Leo Am Kim, M.D., Assistant Professor of Ophthalmology, Massachusetts Eye and Ear Infirmary
ClinicalTrials.gov Identifier:	NCT06033703
Other Study ID Numbers:	2022P000152
First Posted:	September 13, 2023 Key Record Dates
Last Update Posted:	January 10, 2024
Last Verified:	January 2024

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Leo Am Kim, M.D., Massachusetts Eye and Ear Infirmary:


Vitrectomy Netarsudil Pharmacokinetics Safety Efficacy

Additional relevant MeSH terms:

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Retinal Detachment Vitreoretinopathy, Proliferative Dissociative Disorders	Mental Disorders Retinal Diseases Eye Diseases

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