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

Primary Purpose

Rhegmatogenous Retinal Detachment, Proliferative Vitreoretinopathy

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Netarsudil Ophthalmic
Sponsored by
Massachusetts Eye and Ear Infirmary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rhegmatogenous Retinal Detachment focused on measuring Vitrectomy, Netarsudil, Pharmacokinetics, Safety, Efficacy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Primary retinal detachment, Phakic group

    Primary retinal detachment, Pseudophakic group

    Secondary retinal detachment, Phakic group

    Secondary retinal detachment, Pseudophakic group

    Arm Description

    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.

    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.

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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)
    Serious adverse events
    Unexpected serious adverse events

    Secondary Outcome Measures

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

    Full Information

    First Posted
    August 17, 2023
    Last Updated
    September 9, 2023
    Sponsor
    Massachusetts Eye and Ear Infirmary
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06033703
    Brief Title
    Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Retinal Detachment
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    September 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Massachusetts Eye and Ear Infirmary

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rhegmatogenous Retinal Detachment, Proliferative Vitreoretinopathy
    Keywords
    Vitrectomy, Netarsudil, Pharmacokinetics, Safety, Efficacy

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    48 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Primary retinal detachment, Phakic group
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Primary retinal detachment, Pseudophakic group
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Secondary retinal detachment, Phakic group
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Secondary retinal detachment, Pseudophakic group
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Netarsudil Ophthalmic
    Other Intervention Name(s)
    Rhopressa
    Intervention Description
    Topical administration of Netarsudil
    Primary Outcome Measure Information:
    Title
    The concentration of netarsudil in the vitreous to assess its pharmacokinetic properties.
    Description
    Netarsudil concentration in the posterior segment of the eye, using High-performance liquid chromatography (HPLC)
    Time Frame
    Through study completion, an average of 1 year
    Title
    Serious adverse events
    Description
    Unexpected serious adverse events
    Time Frame
    Day 1, 7, 28, 56, 84, 126, and 168 after surgery
    Secondary Outcome Measure Information:
    Title
    Number of operations within 3 months
    Description
    Total number of operation during the first 3 months after surgery
    Time Frame
    Day 84 after surgery
    Title
    Final attachment status at last follow-up
    Description
    Status of the retina (attached versus detached) at last follow-up visit
    Time Frame
    Day 168 after surgery
    Title
    Visual acuity
    Description
    Best-corrected visual acuity measured using Snellen chart
    Time Frame
    Day 1, 7, 28, 56, 84, 126, and 168 after surgery
    Title
    Spectral domain optical coherence tomography (SD-OCT) of the macula
    Description
    Status of the macula (mac-on versus mac-off)
    Time Frame
    Day 1, 7, 28, 56, 84, 126, and 168 after surgery
    Title
    Adverse events
    Description
    Adverse events including conjunctival injection, subconjunctival hemorrhage, and corneal verticillata, eye irritation, reticular edema of the cornea, hypotony
    Time Frame
    Day 1, 7, 28, 56, 84, 126, and 168 after surgery

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Leo Kim, MD, PhD
    Phone
    6175237900
    Email
    Leo_Kim@meei.harvard.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Center for Clinical Research Operations (CCRO)
    Phone
    6175736060
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Leo Kim, MD, PhD
    Organizational Affiliation
    Massachusetts Eye and Ear
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    28609185
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    32826769
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    33758139
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    30653957
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    29199013
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    30318038
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    32289295
    Citation
    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.
    Results Reference
    background
    PubMed Identifier
    33369939
    Citation
    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.
    Results Reference
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    Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Retinal Detachment

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