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

NCT ID: NCT02834559

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 326 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-27
• Study Completion Date: 2020-06-15

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.

Conditions

Rhegmatogenous Retinal Detachment; High-risk for Proliferative Vitreoretinopathy (PVR)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Adjuvant therapy with 5-FU and LMWH

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).

Group Type: ACTIVE_COMPARATOR

5-fluorouracil and low molecular weight heparin

Intervention Type: DRUG

Intraoperative adjuvant application of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) via intraocular infusion during routine pars plana vitrectomy (PPV).

Standard of care

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Routinely used intraocular infusion with balanced salt solution (BSS) during routine pars plana vitrectomy (PPV).

Interventions

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).

Intervention Type: DRUG

Placebo

Routinely used intraocular infusion with balanced salt solution (BSS) during routine pars plana vitrectomy (PPV).

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

The Clinical Trials Centre Cologne

OTHER

Sponsor Role: collaborator

Pharmacy of the University Hospital Erlangen

UNKNOWN

Sponsor Role: collaborator

Institute of Medical Statistics, Informatics and Epidemiology (IMSIE)

UNKNOWN

Sponsor Role: collaborator

Universitätsklinikum Köln

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Friederike Schaub, PD. Dr.

Role: PRINCIPAL_INVESTIGATOR

Department of Ophthalmology, University of Cologne

Locations

Augenklinik Uniklinik Freiburg

Freiburg im Breisgau, Baden-Wurttemberg, Germany

STZ eyetrial am Department für Augenheilkunde

Tübingen, Baden-Wurttemberg, Germany

Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf

Hamburg, City state of Hamburg, Germany

Augenklinik Uniklinik Bonn

Bonn, North Rhine-Westphalia, Germany

Augenklinik der Universität zu Köln

Cologne, North Rhine-Westphalia, Germany

Universitäts-Augenklinik Düsseldorf

Düsseldorf, North Rhine-Westphalia, Germany

Augenärzte am St. Franziskushospital Münster Augenklinik

Münster, North Rhine-Westphalia, Germany

Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach

Sulzbach, Saarbrücken, Germany

Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde

Leipzig, Saxony, Germany

Universitätsaugenklinik Göttingen

Göttingen, , Germany

Universitätsaugenklinik Kiel

Kiel, , Germany

Augenklinik TU München

München, , Germany

Universitätsaugenklinik Regensburg

Regensburg, , Germany

Countries

Germany

References

Schaub F, Hoerster R, Schiller P, Felsch M, Kraus D, Zarrouk M, Kirchhof B, Fauser S. Prophylactic intravitreal 5-fluorouracil and heparin to prevent proliferative vitreoretinopathy in high-risk patients with retinal detachment: study protocol for a randomized controlled trial. Trials. 2018 Jul 16;19(1):384. doi: 10.1186/s13063-018-2761-x.

Reference Type: DERIVED

PMID: 30012187 (View on PubMed)

Other Identifiers

2015-004731-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

uni-koeln-1782

Identifier Type: -

Identifier Source: org_study_id