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

Rhegmatogenous Retinal Detachment Clinical Trial

— PRIVENT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02834559
• Other study ID #: uni-koeln-1782
• Secondary ID: 2015-004731-12
• Status: Completed
• Phase: Phase 3
• Start date: October 27, 2016
• Est. completion date: June 15, 2020

Study information

• Verified date: April 2022
• Source: Universitätsklinikum Köln
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: June 15, 2020
• Est. primary completion date: June 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Dissociative Disorders
• High-risk for Proliferative Vitreoretinopathy (PVR)
• Retinal Detachment
• Rhegmatogenous Retinal Detachment

Intervention

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

Locations

Country	Name	City	State
Germany	Augenklinik Uniklinik Bonn	Bonn	NRW
Germany	Universitäts-Augenklinik Düsseldorf	Dusseldorf	NRW
Germany	Augenklinik Uniklinik Freiburg	Freiburg	BW
Germany	Universitätsaugenklinik Göttingen	Göttingen
Germany	Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf	Hamburg	HH
Germany	Universitätsaugenklinik Kiel	Kiel
Germany	Augenklinik der Universität zu Köln	Koln	NRW
Germany	Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde	Leipzig	Sachsen
Germany	Augenklinik TU München	München
Germany	Augenärzte am St. Franziskushospital Münster Augenklinik	Munster	NRW
Germany	Universitätsaugenklinik Regensburg	Regensburg
Germany	Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach	Sulzbach	Saarbrücken
Germany	STZ eyetrial am Department für Augenheilkunde	Tübingen	BW

Sponsors (5)

Lead Sponsor	Collaborator
Universitätsklinikum Köln	German Research Foundation, Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), Pharmacy of the University Hospital Erlangen, The Clinical Trials Centre Cologne

Country where clinical trial is conducted

Germany, 

Outcome

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