Clinical trial NCT02834559: Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.
Official title: Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rhegmatogenous Retinal Detachment
High-risk for Proliferative Vitreoretinopathy (PVR)
Lead sponsor: Universitätsklinikum Köln
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: The Clinical Trials Centre Cologne
name: Pharmacy of the University Hospital Erlangen
name: Institute of Medical Statistics, Informatics and Epidemiology (IMSIE)
First posted: 2016-07-15
Enrollment: 326
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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).

Primary outcomes:
measure: Proliferative Vitreoretinopathy (PVR) grade CP (posterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]
timeFrame: within 12 weeks
Secondary outcomes:
measure: PVR grade CP 1 or higher [yes/no]
timeFrame: within 6 weeks
measure: PVR grade CA (anterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]
timeFrame: within 6 weeks and 12 weeks
measure: Degree of PVR (PVR grade CA 1-12, PVR grade CP 1-12 (in clock hours))
timeFrame: within 6 weeks and 12 weeks
measure: Best Corrected Visual Acuity (BCVA) measured by ETDRS charts
timeFrame: within 6 weeks and 12 weeks
measure: Retinal reattachment after primary intervention [yes/no]
timeFrame: within 6 weeks and 12 weeks
measure: Number of retinal re-detachments and if present due to PVR [yes/no]
timeFrame: within 6 weeks and 12 weeks
measure: Number and extent of surgical procedures necessary to achieve retinal reattachment
timeFrame: within 12 weeks
measure: Occurrence of at least one drug-related adverse event that affects the study eye [yes/no]
timeFrame: within 12 weeks
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Augenklinik Uniklinik Freiburg
state: BW
city: Tübingen
country: Germany
facility: STZ eyetrial am Department für Augenheilkunde
state: BW
city: Hamburg
country: Germany
facility: Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf
state: HH
city: Bonn
country: Germany
facility: Augenklinik Uniklinik Bonn
state: NRW
city: Dusseldorf
country: Germany
facility: Universitäts-Augenklinik Düsseldorf
state: NRW
city: Koln
country: Germany
facility: Augenklinik der Universität zu Köln
state: NRW
city: Munster
country: Germany
facility: Augenärzte am St. Franziskushospital Münster Augenklinik
state: NRW
city: Sulzbach
country: Germany
facility: Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach
state: Saarbrücken
city: Leipzig
country: Germany
facility: Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde
state: Sachsen
city: Göttingen
country: Germany
facility: Universitätsaugenklinik Göttingen
city: Kiel
country: Germany
facility: Universitätsaugenklinik Kiel
city: München
country: Germany
facility: Augenklinik TU München
city: Regensburg
country: Germany
facility: Universitätsaugenklinik Regensburg
Study officials:
affiliation: Department of Ophthalmology, University of Cologne
name: Friederike Schaub, PD. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.