Intravitreal Infliximab for Proliferative Vitreoretinopathy

NCT ID: NCT04891991

Last Updated: 2024-01-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-26

Study Completion Date

2023-11-10

Brief Summary

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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

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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.

Conditions

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Rhegmatogenous Retinal Detachment Proliferative Vitreoretinopathy Retinal Detachment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Infliximab group

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

Group Type ACTIVE_COMPARATOR

Intravitreal infliximab

Intervention Type DRUG

1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.

Pars plana vitrectomy

Intervention Type PROCEDURE

Standard pars plana vitrectomy

Standard of care group

This group will undergo standard pars plana vitrectomy.

Group Type SHAM_COMPARATOR

Pars plana vitrectomy

Intervention Type PROCEDURE

Standard pars plana vitrectomy

Interventions

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Intravitreal infliximab

1 mg/0.05 mL of infliximab will be injected intravitreally at the end of pars plana vitrectomy.

Intervention Type DRUG

Pars plana vitrectomy

Standard pars plana vitrectomy

Intervention Type PROCEDURE

Other Intervention Names

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Remicade

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cairo University

OTHER

Sponsor Role lead

Responsible Party

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Ayman Gehad Elnahry

Lecturer of Ophthalmology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ayman G Elnahry, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Hany S Hamza, MD, PhD

Role: STUDY_CHAIR

Cairo University

Ahmed M Younes, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Ahmed A Abdel-Kader, MD, PhD

Role: STUDY_DIRECTOR

Cairo University

Ahmed M Abdelbaki, MD, PhD

Role: STUDY_DIRECTOR

Cairo University

Locations

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Cairo University

Cairo, , Egypt

Site Status

Countries

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Egypt

References

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Nagasaki H, Shinagawa K, Mochizuki M. Risk factors for proliferative vitreoretinopathy. Prog Retin Eye Res. 1998 Jan;17(1):77-98. doi: 10.1016/s1350-9462(97)00007-4.

Reference Type BACKGROUND
PMID: 9537796 (View on PubMed)

Pastor JC. Proliferative vitreoretinopathy: an overview. Surv Ophthalmol. 1998 Jul-Aug;43(1):3-18. doi: 10.1016/s0039-6257(98)00023-x.

Reference Type BACKGROUND
PMID: 9716190 (View on PubMed)

Pastor JC, de la Rua ER, Martin F. Proliferative vitreoretinopathy: risk factors and pathobiology. Prog Retin Eye Res. 2002 Jan;21(1):127-44. doi: 10.1016/s1350-9462(01)00023-4.

Reference Type BACKGROUND
PMID: 11906814 (View on PubMed)

Pennock S, Haddock LJ, Mukai S, Kazlauskas A. Vascular endothelial growth factor acts primarily via platelet-derived growth factor receptor alpha to promote proliferative vitreoretinopathy. Am J Pathol. 2014 Nov;184(11):3052-68. doi: 10.1016/j.ajpath.2014.07.026. Epub 2014 Sep 26.

Reference Type BACKGROUND
PMID: 25261788 (View on PubMed)

Charteris DG, Sethi CS, Lewis GP, Fisher SK. Proliferative vitreoretinopathy-developments in adjunctive treatment and retinal pathology. Eye (Lond). 2002 Jul;16(4):369-74. doi: 10.1038/sj.eye.6700194.

Reference Type BACKGROUND
PMID: 12101443 (View on PubMed)

Leiderman YI, Miller JW. Proliferative vitreoretinopathy: pathobiology and therapeutic targets. Semin Ophthalmol. 2009 Mar-Apr;24(2):62-9. doi: 10.1080/08820530902800082.

Reference Type BACKGROUND
PMID: 19373688 (View on PubMed)

Heimann H, Bartz-Schmidt KU, Bornfeld N, Weiss C, Hilgers RD, Foerster MH; Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment Study Group. Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment: a prospective randomized multicenter clinical study. Ophthalmology. 2007 Dec;114(12):2142-54. doi: 10.1016/j.ophtha.2007.09.013.

Reference Type BACKGROUND
PMID: 18054633 (View on PubMed)

Savur F, Aydemir O, Ilhan N. The effect of infliximab and octreotide on cytokine levels experimental proliferative vitreoretinopathy. Cutan Ocul Toxicol. 2020 Mar;39(1):61-66. doi: 10.1080/15569527.2019.1701000. Epub 2019 Dec 17.

Reference Type BACKGROUND
PMID: 31809602 (View on PubMed)

Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behcet disease: a pilot study in 15 patients. Am J Ophthalmol. 2012 Sep;154(3):534-541.e1. doi: 10.1016/j.ajo.2012.03.035. Epub 2012 Jul 11.

Reference Type BACKGROUND
PMID: 22789563 (View on PubMed)

Pascual-Camps I, Hernandez-Martinez P, Monje-Fernandez L, Dolz-Marco R, Gallego-Pinazo R, Wu L, Arevalo JF, Diaz-Llopis M. Update on intravitreal anti-tumor necrosis factor alpha therapies for ocular disorders. J Ophthalmic Inflamm Infect. 2014 Oct 15;4:26. doi: 10.1186/s12348-014-0026-8. eCollection 2014.

Reference Type BACKGROUND
PMID: 25825604 (View on PubMed)

Pastor JC, Rojas J, Pastor-Idoate S, Di Lauro S, Gonzalez-Buendia L, Delgado-Tirado S. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical consequences. Prog Retin Eye Res. 2016 Mar;51:125-55. doi: 10.1016/j.preteyeres.2015.07.005. Epub 2015 Jul 21.

Reference Type BACKGROUND
PMID: 26209346 (View on PubMed)

Hamza MM, Macky TA, Sidky MK, Ragab G, Soliman MM. INTRAVITREAL INFLIXIMAB IN REFRACTORY UVEITIS IN BEHCET'S DISEASE: A Safety and Efficacy Clinical Study. Retina. 2016 Dec;36(12):2399-2408. doi: 10.1097/IAE.0000000000001109.

Reference Type BACKGROUND
PMID: 27870802 (View on PubMed)

Korthagen NM, van Bilsen K, Swagemakers SM, van de Peppel J, Bastiaans J, van der Spek PJ, van Hagen PM, Dik WA. Retinal pigment epithelial cells display specific transcriptional responses upon TNF-alpha stimulation. Br J Ophthalmol. 2015 May;99(5):700-4. doi: 10.1136/bjophthalmol-2014-306309. Epub 2015 Feb 13.

Reference Type BACKGROUND
PMID: 25680620 (View on PubMed)

Pennock S, Haddock LJ, Eliott D, Mukai S, Kazlauskas A. Is neutralizing vitreal growth factors a viable strategy to prevent proliferative vitreoretinopathy? Prog Retin Eye Res. 2014 May;40:16-34. doi: 10.1016/j.preteyeres.2013.12.006. Epub 2014 Jan 9.

Reference Type BACKGROUND
PMID: 24412519 (View on PubMed)

Other Identifiers

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CU272021

Identifier Type: -

Identifier Source: org_study_id

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