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FIXER: Intravitreal Infliximab for Proliferative Vitreoretinopathy

Sponsor
Cairo University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04891991
Collaborator
(none)
66
Enrollment
1
Location
2
Arms
23.5
Anticipated Duration (Months)
2.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Intravitreal infliximab
  • Procedure: Pars plana vitrectomy
 Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
66 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Primary Purpose:
Treatment
Official Title:
Treatment of Proliferative Vitreoretinopathy With Intravitreal Infliximab
Actual Study Start Date :
Nov 26, 2021
Anticipated Primary Completion Date :
Nov 10, 2023
Anticipated Study Completion Date :
Nov 10, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Infliximab group

This group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.

Drug: Intravitreal infliximab
1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.
Other Names:
  • Remicade

    • Procedure: Pars plana vitrectomy
    Standard pars plana vitrectomy
    Sham Comparator: Standard of care group

    This group will undergo standard pars plana vitrectomy.

    Procedure: Pars plana vitrectomy
    Standard pars plana vitrectomy

    Outcome Measures

    Primary Outcome Measures

    1. Anatomical success [9 months]

      Anatomical Success will be defined as stable complete retinal reattachment following pars plana vitrectomy and silicone oil removal.

    Secondary Outcome Measures

    1. Visual acuity [1, 3, 6, and 9 months]

      Best corrected visual acuity will be measured at follow up visits using standard Snellen charts.

    2. Macular structure [1, 3, 6, and 9 months]

      Optical coherence tomography will be done at each follow up visit to assess the structure of the macula.

    3. Macular vascularity [7 months]

      Optical coherence tomography angiography will be done at each follow up visit to assess macular vascular density.

    4. Macular function [7 months]

      Macular function will be assessed during follow up visits using multifocal electroretinography

    5. Single operation success rate [9 months]

      The rate of successful retinal reattachment following a single operation will be calculated.

    6. Recurrence rate [9 months]

      Cumulative rate of recurrence of retinal detachment and reoperation following the primary surgery will be calculated during the study period.

    7. Epiretinal proliferative [1, 3, 6, and 9 months]

      The formation of significant epiretinal proliferation will be assessed clinically at each follow up visit.

    Eligibility Criteria

    Criteria

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cairo University Cairo Egypt 11956

    Sponsors and Collaborators

    • Cairo University

    Investigators

    • Principal Investigator: Ayman G Elnahry, MD, PhD, Cairo University
    • Study Chair: Hany S Hamza, MD, PhD, Cairo University
    • Principal Investigator: Ahmed M Younes, MD, MSc, Cairo University
    • Study Director: Ahmed A Abdel-Kader, MD, PhD, Cairo University
    • Study Director: Ahmed M Abdelbaki, MD, PhD, Cairo University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Ayman Gehad Elnahry, Lecturer of Ophthalmology, Cairo University
    ClinicalTrials.gov Identifier:
    NCT04891991
    Other Study ID Numbers:
    • CU272021
    First Posted:
    May 19, 2021
    Last Update Posted:
    Dec 9, 2021
    Last Verified:
    Nov 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
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:
    Retinal Detachment
    Vitreoretinopathy, Proliferative
    Dissociative Disorders
    Infliximab

    Study Results

    No Results Posted as of Dec 9, 2021