Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.

Phase 3

Completed

• Conditions: Rhegmatogenous Retinal Detachment; High-risk for Proliferative Vitreoretinopathy (PVR)
• Interventions: Drug: 5-fluorouracil and low molecular weight heparin; Drug: Placebo

• Registration Number: NCT02834559
• Lead Sponsor: Universitätsklinikum Köln

Brief Summary

This study investigates the effectiveness of a simple treatment to prevent proliferative vitreoretinopathy (PVR).

Intraoperative intravitreal 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) is used as a prophylactic therapy in high-risk patients with primary rhegmatogenous retinal detachment (RRD). Our major motivation is to reduce the incidence of PVR in the group that receives the trial drug.

Detailed Description

Proliferative vitreoretinopathy (PVR) is a common cause for postoperative failure after vitreoretinal surgery for primary RRD. There is no standard-therapy to prevent PVR. Several attempts using chemotherapeutic agents have been undertaken to prevent this proliferation-process, but none of these was introduced into routine clinical practice.

Until recently, it has been challenging to identify patients with high risk for postoperative PVR formation. This is especially important, because in this trial treatment with the trial drug will be restricted to patients at high risk for PVR only.

Patients are assigned to the following treatment arms (1:1):

(A) Intraoperative adjuvant application of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV) in high-risk patients for proliferative vitreoretinopathy (PVR) with primary rhegmatogenous retinal detachment (RRD).

Versus:

(B) Routinely used intraocular infusion with balanced salt solution (BSS) during routine PPV.

Study Timeline

• Study First Submitted: 2016-07-12
• Study First Submitted QC: 2016-07-12
• Study First Posted: 2016-07-15
• Study Start: 2016-10-27
• Primary Completion: 2020-06-15
• Study Completion: 2020-06-15
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-04
• Last Update Posted: 2022-04-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 326

Inclusion Criteria

1. Primary rhegmatogenous retinal detachment (< 4 weeks) in study eye
2. Scheduled for pars plana vitrectomy for retinal detachment repair without combined cataract surgery in study eye
3. Elevated protein levels in anterior chamber fluid (laser-flare value ≥ 15.0 pc/ms) in study eye
4. Female or male patient ≥ 18 years of age
5. Written informed consent

Exclusion Criteria

1. Retinal detachment lasting > 4 weeks in study eye
2. Traumatic retinal detachment in study eye
3. Giant retinal tears in study eye (size > 3 clock hours)
4. Visual pre-existing PVR grade C in study eye
5. Retinal dystrophies in study eye
6. Scheduled for combined pars plana vitrectomy and cataract surgery for retinal detachment repair in study eye
7. Chronic inflammatory conditions in study eye
8. Active retinal vascular disease in study eye
9. Proliferative diabetic retinopathy in study eye
10. Manifest uveitis in study eye
11. Endophthalmitis in study eye
12. Perforating and non-perforating trauma in study eye
13. Malignant intraocular tumor in study eye
14. Aphakia in study eye
15. Uncontrolled glaucoma or ocular hypertension in study eye (intraocular pressure ≥ 30 mmHg despite IOP lowering therapy)
16. Previous intraocular surgery except uncomplicated cataract surgery with posterior chamber lens implantation in study eye
17. Cataract surgery in study eye ≤ 3 months ago
18. Previous retinal procedures (laserpexy, cryopexy, intravitreal gas-injection, anti-VEGF or corticosteroid-injection) in study eye ≤ 6 months
19. Other uncontrolled ophthalmologic disorders
20. Single eyed patients (BCVA of fellow eye > 1.0 log MAR, < 0.1 decimal, < 1/10 tenth, or < 6/60 Snellen fraction [m])
21. Evidence or history of alcohol, medication or drug dependency within the last 12 months.
22. Evidence or history (within the last 12 months) of neurotic personality, psychiatric illness that requires or required treatment, epilepsy or suicide risk.
23. Systemic disorders not compatible with adjuvant application of 5-FU and LMWH via intraocular infusion, or not compatible with the local or general anesthesia
24. Any therapy with immunosuppressant or chemotherapy ≤ 3 months and during the trial period
25. Participation in another trial of IMPs or devices parallel to, or less than 3 months before screening, or previous participation in this trial.
26. Known to or suspected of not being able to comply with the protocol.
27. Inability to understand the rationale of this trial or the study aim
28. Any dependency of the patient to the Investigator or the trial site, e.g. employees with direct involvement in the proposed trial or in other trials under the direction of this Investigator or trial site, as well as family members of the employees or the Investigator.
29. Positive urine pregnancy test, pregnancy or breastfeeding mother.
30. Women of child bearing potential without satisfactory contraception, i.e. hormonal contraceptives for at least 14 days before trial enrolment, IUD, double barrier (women of child bearing age must be counselled about the use of adequate contraception).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adjuvant therapy with 5-FU and LMWH	5-fluorouracil and low molecular weight heparin	Intraoperative adjuvant application of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV) in high-risk patients for proliferative vitreoretinopathy (PVR) with primary rhegmatogenous retinal detachment (RRD).
Standard of care	Placebo	Routinely used intraocular infusion with balanced salt solution (BSS) during routine pars plana vitrectomy (PPV) in high-risk patients for proliferative vitreoretinopathy (PVR) with primary rhegmatogenous retinal detachment (RRD).

Primary Outcome Measures

Name	Time	Method
Proliferative Vitreoretinopathy (PVR) grade CP (posterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]	within 12 weeks

Secondary Outcome Measures

Name	Time	Method
Occurrence of at least one drug-related adverse event that affects the study eye [yes/no]	within 12 weeks
PVR grade CP 1 or higher [yes/no]	within 6 weeks
Degree of PVR (PVR grade CA 1-12, PVR grade CP 1-12 (in clock hours))	within 6 weeks and 12 weeks
Best Corrected Visual Acuity (BCVA) measured by ETDRS charts	within 6 weeks and 12 weeks
PVR grade CA (anterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]	within 6 weeks and 12 weeks
Number and extent of surgical procedures necessary to achieve retinal reattachment	within 12 weeks
Retinal reattachment after primary intervention [yes/no]	within 6 weeks and 12 weeks
Number of retinal re-detachments and if present due to PVR [yes/no]	within 6 weeks and 12 weeks

Trial Locations

Locations (13)

Augenklinik Uniklinik Freiburg; 🇩🇪 Freiburg, BW, Germany

STZ eyetrial am Department für Augenheilkunde; 🇩🇪 Tübingen, BW, Germany

Augenklinik Uniklinik Bonn; 🇩🇪 Bonn, NRW, Germany

Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf; 🇩🇪 Hamburg, HH, Germany

Universitäts-Augenklinik Düsseldorf; 🇩🇪 Dusseldorf, NRW, Germany

Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde; 🇩🇪 Leipzig, Sachsen, Germany

Augenklinik der Universität zu Köln; 🇩🇪 Koln, NRW, Germany

Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach; 🇩🇪 Sulzbach, Saarbrücken, Germany

Augenärzte am St. Franziskushospital Münster Augenklinik; 🇩🇪 Munster, NRW, Germany

Universitätsaugenklinik Göttingen; 🇩🇪 Göttingen, Germany

Universitätsaugenklinik Kiel; 🇩🇪 Kiel, Germany

Augenklinik TU München; 🇩🇪 München, Germany

Universitätsaugenklinik Regensburg; 🇩🇪 Regensburg, Germany