Intravitreal Infliximab for Proliferative Vitreoretinopathy (FIXER)
Primary Purpose
Rhegmatogenous Retinal Detachment, Proliferative Vitreoretinopathy, Retinal Detachment
Status
Active
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Intravitreal infliximab
Pars plana vitrectomy
Sponsored by
About this trial
This is an interventional treatment trial for Rhegmatogenous Retinal Detachment
Eligibility Criteria
Inclusion Criteria:
- Age: more than or equal to 18 years
- Primary rhegmatogenous retinal detachment with proliferative vitreoretinopathy more than or equal to grade C
Exclusion Criteria:
- Patients with a history of open globe injury
- Recurrent retinal detachment or primary failed retinal detachment surgery
- History of vitreoretinal procedure
- Retinal vascular diseases (Diabetic retinopathy, retinal vein occlusion,...etc)
- Pregnant or breastfeeding females
- Inability to attend regular follow-up visits
- History of pulmonary or extra-pulmonary tuberculosis.
Sites / Locations
- Cairo University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Infliximab group
Standard of care group
Arm Description
This group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.
This group will undergo standard pars plana vitrectomy.
Outcomes
Primary Outcome Measures
Anatomical success
Anatomical Success will be defined as stable complete retinal reattachment following pars plana vitrectomy and silicone oil removal.
Secondary Outcome Measures
Visual acuity
Best corrected visual acuity will be measured at follow up visits using standard Snellen charts.
Macular structure
Optical coherence tomography will be done at each follow up visit to assess the structure of the macula.
Macular vascularity
Optical coherence tomography angiography will be done at each follow up visit to assess macular vascular density.
Macular function
Macular function will be assessed during follow up visits using multifocal electroretinography
Single operation success rate
The rate of successful retinal reattachment following a single operation will be calculated.
Recurrence rate
Cumulative rate of recurrence of retinal detachment and reoperation following the primary surgery will be calculated during the study period.
Epiretinal proliferative
The formation of significant epiretinal proliferation will be assessed clinically at each follow up visit.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04891991
Brief Title
Intravitreal Infliximab for Proliferative Vitreoretinopathy
Acronym
FIXER
Official Title
Treatment of Proliferative Vitreoretinopathy With Intravitreal Infliximab
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 26, 2021 (Actual)
Primary Completion Date
November 10, 2023 (Anticipated)
Study Completion Date
November 10, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cairo University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis.
Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with the retinal pigment epithelium (RPE) cell contribute to the initiation of PVR. This may occur through the action of TNF-α on the RPE cells inducing changes in cellular morphologies that lead to the formation of fibroblastic cells.
Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model.
The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment.
Detailed Description
Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity on both sides of the retinal surface as well as intraretinal fibrosis.
The incidence of PVR in all cases of retinal detachment is estimated to be 5- 10%. The incidence of PVR has largely remained unchanged in prospective studies despite the evolution of vitreoretinal techniques over the past 25 years, including valved trocars and smaller gauge instrumentation.
Numerous risk factors for the development of PVR have been identified. Almost all risk factors for PVR are associated with intravitreal dispersion of retinal pigment epithelial cells or breakdown of the blood-ocular barrier. Following a retinal break, the retinal pigment epithelial (RPE) cells are exposed to the vitreous cavity to react to growth factors and cytokines in the vitreous, resulting in a forward feedback to secret more growth factors and cytokines to further stimulate cellular responses.
Multiple therapeutic agents have been tried as an adjunctive to retinal detachment surgery for PVR with no consistent efficacy. Tumor necrosis factor-α (TNF-α), which is a prominent inflammatory cytokine, is secreted in response to trauma, infection, and inflammation. It is a key mediator of ocular inflammation and its interactions with RPE cells contribute to the initiation of PVR. This is because TNF-α was found to act on the RPE cells consequently inducing changes in cellular morphologies leading to the formation of fibroblastic cells. Additionally, if TNF-α is combined with other growth factors, a strong synergistic effect can be induced to form epithelial-mesenchymal transition (EMT)-associated fibrotic focus.
Infliximab (Remicade; Janssen Biotech, Horsham, PA, USA) is a mouse-human chimeric antibody that neutralizes the biological activity of TNF-α by high-affinity binding to the soluble and transmembrane forms of TNF-α, therefore preventing the effective binding of TNF-α with its receptors. Infliximab is used in the treatment of various ocular and systemic inflammatory conditions. Furthermore, intravitreal infliximab has been used for the treatment of various ocular diseases and has proven to be generally safe for the short term in inflammatory ocular conditions. A recent study showed that intravitreal infliximab can inhibit the development of PVR and reduce levels of cytokines in an experimental dispase-induced PVR model.
The purpose of this randomized controlled trial is to evaluate the efficacy of intravitreal infliximab injection as an adjunct to pars plana vitrectomy in the treatment of PVR associated with primary rhegmatogenous retinal detachment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhegmatogenous Retinal Detachment, Proliferative Vitreoretinopathy, Retinal Detachment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
66 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Infliximab group
Arm Type
Active Comparator
Arm Description
This group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.
Arm Title
Standard of care group
Arm Type
Sham Comparator
Arm Description
This group will undergo standard pars plana vitrectomy.
Intervention Type
Drug
Intervention Name(s)
Intravitreal infliximab
Other Intervention Name(s)
Remicade
Intervention Description
1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.
Intervention Type
Procedure
Intervention Name(s)
Pars plana vitrectomy
Intervention Description
Standard pars plana vitrectomy
Primary Outcome Measure Information:
Title
Anatomical success
Description
Anatomical Success will be defined as stable complete retinal reattachment following pars plana vitrectomy and silicone oil removal.
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Visual acuity
Description
Best corrected visual acuity will be measured at follow up visits using standard Snellen charts.
Time Frame
1, 3, 6, and 9 months
Title
Macular structure
Description
Optical coherence tomography will be done at each follow up visit to assess the structure of the macula.
Time Frame
1, 3, 6, and 9 months
Title
Macular vascularity
Description
Optical coherence tomography angiography will be done at each follow up visit to assess macular vascular density.
Time Frame
7 months
Title
Macular function
Description
Macular function will be assessed during follow up visits using multifocal electroretinography
Time Frame
7 months
Title
Single operation success rate
Description
The rate of successful retinal reattachment following a single operation will be calculated.
Time Frame
9 months
Title
Recurrence rate
Description
Cumulative rate of recurrence of retinal detachment and reoperation following the primary surgery will be calculated during the study period.
Time Frame
9 months
Title
Epiretinal proliferative
Description
The formation of significant epiretinal proliferation will be assessed clinically at each follow up visit.
Time Frame
1, 3, 6, and 9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age: more than or equal to 18 years
Primary rhegmatogenous retinal detachment with proliferative vitreoretinopathy more than or equal to grade C
Exclusion Criteria:
Patients with a history of open globe injury
Recurrent retinal detachment or primary failed retinal detachment surgery
History of vitreoretinal procedure
Retinal vascular diseases (Diabetic retinopathy, retinal vein occlusion,...etc)
Pregnant or breastfeeding females
Inability to attend regular follow-up visits
History of pulmonary or extra-pulmonary tuberculosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ayman G Elnahry, MD, PhD
Organizational Affiliation
Cairo University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hany S Hamza, MD, PhD
Organizational Affiliation
Cairo University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ahmed M Younes, MD, MSc
Organizational Affiliation
Cairo University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ahmed A Abdel-Kader, MD, PhD
Organizational Affiliation
Cairo University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Ahmed M Abdelbaki, MD, PhD
Organizational Affiliation
Cairo University
Official's Role
Study Director
Facility Information:
Facility Name
Cairo University
City
Cairo
ZIP/Postal Code
11956
Country
Egypt
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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Intravitreal Infliximab for Proliferative Vitreoretinopathy
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