Prevention of ProliFerative Vitreoretinopathy with Intravitreal MethotreXate in Primary Retinal DEtachment Repair (FIXER) Trial

NCT06541574 | Recruiting Phase 2 FDA Drug

• 1 other identifier: FIXER-PVR
• Study Type: interventional
• Target: 860
• Locations: 1 country
• Sites: 1

Brief Summary

I. Title Prevention of ProliFerative Vitreoretinopathy with Intravitreal MethotreXate in Primary Retinal DEtachment Repair (FIXER) Trial

• Today's Date: September 18, 2023 II. Principal Investigator
• Principal Investigator: Christopher D. Riemann, M.D. (Cincinnati Eye Institute)
• Email: criemann@cvphealth.com, Phone: 513-708-1979 V. Research Summary Purpose: To evaluate methotrexate for the prevention of PVR after primary rhegmatogenous retinal detachment repair. Methods: Inclusion Criteria:
• Any adult patient, age ≥18 years-old, undergoing primary rhegmatogenous retinal detachment surgery with pars plana vitrectomy at the Cincinnati Eye Institute in Blue Ash, Ohio who is able to give informed consent. Exclusion Criteria:
• Age \<18 years old
• Pregnant patients or patients of child bearing potential unwilling to utilize long term contraception for the 12-week period spanning vitrectomy surgery for retinal detachment repair up until the 3 month postoperative visit.
• History of endophthalmitis, ruptured globe or significant trauma in the affected eye
• Chronic retinal detachment (symptoms greater than or equal to six weeks)
• Any previous previous retinal detachment repair with pars plana vitrectomy, or scleral buckling surgery. Patients having undergone previous pneumatic retinopexy will not be excluded.
• Presence of Grade C PVR: full thickness retinal folds or subretinal bands
• Patients with contraindications to methotrexate, including breastfeeding, pregnancy, attempting to conceive a child or any known hypersensitivity or intolerance to methotrexate
• Patients with diminished mental capacity precluding their ability to give informed consent. Study Design and Randomization This prospective double masked trial will randomize patients into four groups in a 1:1:1:1 fashion. All attending surgeons and patients will be masked to group randomization. Randomization into four groups will occur on the day of surgery by the Cincinnati Eye Institute's pharmacist, Deepali Chachare. Group A will consist of ≥ 150 patients receiving intraoperative infusion with balanced salt solution containing methotrexate (40mg/500mL BSS), and methotrexate intravitreal injections (400mcg/0.05mL) at postoperative weeks 1, 3, 6, and 10. Group B will consist of ≥ 150 patients receiving intraoperative balanced salt solution infusion containing methotrexate, and sham intravitreal injections at postoperative weeks 1, 3, 6, and 10. Group C will consist of ≥ 150 patients receiving a balanced salt solution infusion without methotrexate, and methotrexate injections at postoperative weeks 1, 3, 6, and 10. Group D will consist of ≥ 150 patients receiving intraoperative balanced salt solution infusion without methotrexate, and sham intravitreal injections at postoperative weeks 1, 3, 6, and 10.

Conditions

Proliferative Vitreoretinopathy; Rhegmatogenous Retinal Detachment

Keywords

Proliferative Vitreoretinopathy; Rhegmatogenous Retinal Detachment

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  Percentage of patients achieving single Surgery Success rate for primary Rhegmatogenous Retinal Detachment repair in each group.

  Month 12

Secondary Outcomes (6)

• number of retinal detachment repair reoperations

  12 months

• Visual Acuity

  12 months

• Time to Re-detachment from PVR

  12 months

• methotrexate-associated corneal epitheliopathy

  12 months

• Complications

  12 months

Study Arms (4)

Control Group

SHAM COMPARATOR

receiving no methotrexate

Drug: Sham Injection

Injection group

EXPERIMENTAL

receiving standard surgery without intraoperative methotrexate followed by postoperative 400µg intravitreal methotrexate injections 1, 3, 6, and 10 weeks after surgery.

Drug: Methotrexate Injection

Infusion Group

EXPERIMENTAL

receiving surgery with intraoperative intraocular methotrexate infusion as described above and postoperative sham injections.

Drug: Methotrexate Infusion

Combined Infusion/Injection group

EXPERIMENTAL

receiving both intraoperative intraocular methotrexate infusion and postoperative 400µg intravitreal methotrexate injections 1, 3, 6, and 10 weeks after surgery.

Drug: Methotrexate Injection; Drug: Methotrexate Infusion

Interventions

Methotrexate Injection DRUG

Methotrexate injection

Combined Infusion/Injection group; Injection group

Methotrexate Infusion DRUG

Methotrexate Infusion

Combined Infusion/Injection group; Infusion Group

Sham Injection DRUG

Sham Injection

Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any adult patient, age \> 18 years-old, undergoing primary rhegmatogenous retinal detachment surgery with pars plana vitrectomy at the Cincinnati Eye Institute in Blue Ash, Ohio who is able to give informed consent.

You may not qualify if:

• Age \<18 years-old
• Pregnant patients or patients of child bearing potential unwilling to utilize long term contraception for the 12-week period spanning vitrectomy surgery for retinal detachment repair up until the 3 month postoperative visit.
• History of endophthalmitis, ruptured globe or significant trauma in the affected eye
• Chronic retinal detachment (symptoms \> six weeks)
• Any previous previous retinal detachment repair with pars plana vitrectomy, or scleral buckling surgery. Patients having undergone previous pneumatic retinopexy will not be excluded.
• Presence of Grade C PVR: full thickness retinal folds or subretinal bands
• Patients with contraindications to methotrexate, including breastfeeding, pregnancy, attempting to conceive a child or any known hypersensitivity or intolerance to methotrexate
• Patients with diminished mental capacity precluding their ability to give informed consent.

Sponsors & Collaborators

• Cincinnati Eye Institute, Southwest Ohio: lead

Study Sites (1)

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

RECRUITING

Related Publications (17)

• McCannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011 Apr;31(4):654-61. doi: 10.1097/IAE.0b013e31820a67e4.

  PMID: 21330939 BACKGROUND

• Dave VP, Pathengay A, Schwartz SG, Flynn HW Jr. Endophthalmitis following pars plana vitrectomy: a literature review of incidence, causative organisms, and treatment outcomes. Clin Ophthalmol. 2014 Oct 31;8:2183-8. doi: 10.2147/OPTH.S71293. eCollection 2014.

  PMID: 25382968 BACKGROUND

• Habot-Wilner Z, Frenkel S, Pe'er J. Efficacy and safety of intravitreal methotrexate for vitreo-retinal lymphoma - 20 years of experience. Br J Haematol. 2021 Jul;194(1):92-100. doi: 10.1111/bjh.17451. Epub 2021 Apr 26.

  PMID: 33900619 BACKGROUND

• Choudhury H, Jindal A, Pathengay A, Flynn HW Jr. An outbreak of Ralstonia pickettii endophthalmitis following intravitreal methotrexate injection. Clin Ophthalmol. 2015 Jun 23;9:1117-20. doi: 10.2147/OPTH.S81218. eCollection 2015.

  PMID: 26150690 BACKGROUND

• Zhou X, Zhou X, Shi H, Lai J, Wang Q, Li Y, Chen K, Li Q, Zhou Q, Cao X, Chen B, Xiao J. Reduced frequency of Intravitreal methotrexate injection lowers the risk of Keratopathy in Vitreoretinal lymphoma patients. BMC Ophthalmol. 2020 May 12;20(1):189. doi: 10.1186/s12886-020-01464-3.

  PMID: 32397978 BACKGROUND

• Sadaka A, Sisk RA, Osher JM, Toygar O, Duncan MK, Riemann CD. Intravitreal methotrexate infusion for proliferative vitreoretinopathy. Clin Ophthalmol. 2016 Sep 19;10:1811-1817. doi: 10.2147/OPTH.S111893. eCollection 2016.

  PMID: 27698550 BACKGROUND

• Noble CW, Kim HJ, Pham H, Riemann CD. Prophylactic intravitreal methotrexate for PVR prevention in patients undergoing primary RRD repair with PPV with history of contralateral PVR. American Society of Retina Specialists Annual Meeting. Virtual July 24-26, 2020.

  BACKGROUND

• Ivanisevic M. The natural history of untreated rhegmatogenous retinal detachment. Ophthalmologica. 1997;211(2):90-2. doi: 10.1159/000310766.

  PMID: 9097312 BACKGROUND

• SCHEPENS CL, OKAMURA ID, BROCKHURST RJ. The scleral buckling procedures. I. Surgical techniques and management. AMA Arch Ophthalmol. 1957 Dec;58(6):797-811. doi: 10.1001/archopht.1957.00940010819003. No abstract available.

  PMID: 13478226 BACKGROUND

• Steel D. Retinal detachment. BMJ Clin Evid. 2014 Mar 3;2014:0710.

  PMID: 24807890 BACKGROUND

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

  PMID: 9716190 BACKGROUND

• Rachal WF, Burton TC. Changing concepts of failures after retinal detachment surgery. Arch Ophthalmol. 1979 Mar;97(3):480-3. doi: 10.1001/archopht.1979.01020010230008.

  PMID: 420635 BACKGROUND

• Di Lauro S, Kadhim MR, Charteris DG, Pastor JC. Classifications for Proliferative Vitreoretinopathy (PVR): An Analysis of Their Use in Publications over the Last 15 Years. J Ophthalmol. 2016;2016:7807596. doi: 10.1155/2016/7807596. Epub 2016 Jun 27.

  PMID: 27429798 BACKGROUND

• Chan ES, Cronstein BN. Methotrexate--how does it really work? Nat Rev Rheumatol. 2010 Mar;6(3):175-8. doi: 10.1038/nrrheum.2010.5.

  PMID: 20197777 BACKGROUND

• BSS- basic salt solution. (https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=4bd4d59c-eb3b-4a5e-9eb7-ae95b0a92bea&type=display

  BACKGROUND

• Wang G, Peng X. A Review of Clinical Applications and Side Effects of Methotrexate in Ophthalmology. J Ophthalmol. 2020 Aug 11;2020:1537689. doi: 10.1155/2020/1537689. eCollection 2020.

  PMID: 32850138 BACKGROUND

• Tables of Possible Side Effects for Commonly-Used Oncology Drugs. NIH. (https://ctep.cancer.gov/protocoldevelopment/sideeffects/drugs.htm

  BACKGROUND

MeSH Terms

Conditions

Vitreoretinopathy, Proliferative

Interventions

Methotrexate; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Christopher Riemann, MD

CONTACT

513-708-1979; criemann@cvphealth.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The Doctor Administring the medication are not masked and are not involved with primary follow up of the patients
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 1:1:1:1 randomization strategy into four groups: 1. Control group - receiving no methotrexate 2. Injection group - receiving standard surgery without intraoperative methotrexate followed by postoperative 400µg intravitreal methotrexate injections 1, 3, 6, and 10 weeks after surgery. 3. Infusion group - receiving surgery with intraoperative intraocular methotrexate infusion as described above and postoperative sham injections. 4. Combined Infusion/Injection group - receiving both intraoperative intraocular methotrexate infusion and postoperative 400µg intravitreal methotrexate injections 1, 3, 6, and 10 weeks after surgery.

Study Record Dates

• First Submitted: July 30, 2024
• First Posted: August 7, 2024
• Study Start: March 1, 2024
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

US (1)