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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Rhegmatogenous Retinal Detachment, Proliferative Vitreoretinopathy

Intervention / Treatment
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* Drug: Netarsudil Ophthalmic


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary retinal detachment, Phakic group<br>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<br>* Topical administration of Netarsudil<br>* Other names: Rhopressa;|
| Experimental: Primary retinal detachment, Pseudophakic group<br>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<br>* Topical administration of Netarsudil<br>* Other names: Rhopressa;|
| Experimental: Secondary retinal detachment, Phakic group<br>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<br>* Topical administration of Netarsudil<br>* Other names: Rhopressa;|
| Experimental: Secondary retinal detachment, Pseudophakic group<br>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<br>* Topical administration of Netarsudil<br>* Other names: Rhopressa;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitrectomy, Netarsudil, Pharmacokinetics, Safety, Efficacy