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Rhegmatogenous Retinal DetachmentPhase 2FIXERNCT04891991

Intravitreal Infliximab for Proliferative Vitreoretinopathy

A Phase 2 study testing Intravitreal infliximab and Pars plana vitrectomy in people with Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy, run by Cairo University at 1 site in Egypt.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Intravitreal infliximab and Pars plana vitrectomy
Type of treatment
Surgery or procedure
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
66 participants
Where
1 siteEgypt
Study dates
26 Nov 2021to 10 Nov 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age: more than or equal to 18 years
  • Primary rhegmatogenous retinal detachment with proliferative vitreoretinopathy more than or equal to grade C

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Egypt1 site
  • Cairo University

    Cairo, 11956

Other trials in Egypt

About this study

Official title: Treatment of Proliferative Vitreoretinopathy With Intravitreal Infliximab

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.

Read more

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.

Read the 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.

Being tested
Intravitreal infliximab, Pars plana vitrectomy
Medical subject headings
Vitreoretinopathy, Proliferative, Retinal Detachment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intravitreal infliximabDrug

    Also called Remicade

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

  • Pars plana vitrectomyProcedure or surgery

    Standard pars plana vitrectomy

Study groups in NCT04891991
Study groupRoleWhat they receive
Infliximab groupActive comparatorThis group will receive 1 mg/0.05 mL of intravitreal infliximab at the end of standard pars plana vitrectomy.
Receives: Drug: Intravitreal infliximab; Procedure: Pars plana vitrectomy
Standard of care groupSham comparatorThis group will undergo standard pars plana vitrectomy.
Receives: Procedure: Pars plana vitrectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Anatomical success

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

    Measured: 9 months

Secondary outcomes (7)
  1. Visual acuity

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

    Measured: 1, 3, 6, and 9 months

  2. Macular structure

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

    Measured: 1, 3, 6, and 9 months

  3. Macular vascularity

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

    Measured: 7 months

  4. Macular function

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

    Measured: 7 months

  5. Single operation success rate

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

    Measured: 9 months

  6. Recurrence rate

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

    Measured: 9 months

  7. Epiretinal proliferative

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

    Measured: 1, 3, 6, and 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2021
  2. Study start26 Nov 2021
  3. Primary completion10 Nov 2023
  4. Study completion10 Nov 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04891991
Sponsor's protocol ID
CU272021
Acronym
FIXER
Status last verified
Jan 2024
First submitted
10 May 2021
Last updated
19 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 9537796
  • Pastor JC. Proliferative vitreoretinopathy: an overview. Surv Ophthalmol. 1998 Jul-Aug;43(1):3-18. doi: 10.1016/s0039-6257(98)00023-x.

    PubMed 9716190
  • 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.

    PubMed 11906814
  • 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.

    PubMed 25261788
  • 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.

    PubMed 12101443
  • Leiderman YI, Miller JW. Proliferative vitreoretinopathy: pathobiology and therapeutic targets. Semin Ophthalmol. 2009 Mar-Apr;24(2):62-9. doi: 10.1080/08820530902800082.

    PubMed 19373688
  • 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.

    PubMed 18054633
  • 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.

    PubMed 31809602
  • 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.

    PubMed 22789563
  • 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.

    PubMed 25825604
  • 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.

    PubMed 26209346
  • 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.

    PubMed 27870802
  • 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.

    PubMed 25680620
  • 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.

    PubMed 24412519

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Intravitreal infliximab and Pars plana vitrectomy in people with Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy, run by Cairo University at 1 site in Egypt.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Anatomical success (time frame: 9 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04891991, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2024.

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