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

Sponsor
Universitätsklinikum Köln (Other)
Overall Status
Completed
CT.gov ID
NCT02834559
Collaborator
German Research Foundation (Other), The Clinical Trials Centre Cologne (Other), Pharmacy of the University Hospital Erlangen (Other), Institute of Medical Statistics, Informatics and Epidemiology (IMSIE) (Other)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: 5-fluorouracil and low molecular weight heparin
  • Drug: Placebo
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
326 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.
Actual Study Start Date :
Oct 27, 2016
Actual Primary Completion Date :
Jun 15, 2020
Actual Study Completion Date :
Jun 15, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: 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).

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 Comparator: 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).

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

  1. PVR grade CP 1 or higher [yes/no] [within 6 weeks]

  2. PVR grade CA (anterior - full thickness retinal folds in clock hours) 1 or higher [yes/no] [within 6 weeks and 12 weeks]

  3. Degree of PVR (PVR grade CA 1-12, PVR grade CP 1-12 (in clock hours)) [within 6 weeks and 12 weeks]

  4. Best Corrected Visual Acuity (BCVA) measured by ETDRS charts [within 6 weeks and 12 weeks]

  5. Retinal reattachment after primary intervention [yes/no] [within 6 weeks and 12 weeks]

  6. Number of retinal re-detachments and if present due to PVR [yes/no] [within 6 weeks and 12 weeks]

  7. Number and extent of surgical procedures necessary to achieve retinal reattachment [within 12 weeks]

  8. Occurrence of at least one drug-related adverse event that affects the study eye [yes/no] [within 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Augenklinik Uniklinik Freiburg Freiburg BW Germany 79106
2 STZ eyetrial am Department für Augenheilkunde Tübingen BW Germany 72076
3 Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf Hamburg HH Germany 20246
4 Augenklinik Uniklinik Bonn Bonn NRW Germany 53127
5 Universitäts-Augenklinik Düsseldorf Dusseldorf NRW Germany 40255
6 Augenklinik der Universität zu Köln Koln NRW Germany 50931
7 Augenärzte am St. Franziskushospital Münster Augenklinik Munster NRW Germany 48145
8 Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach Sulzbach Saarbrücken Germany 66280
9 Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde Leipzig Sachsen Germany 04103
10 Universitätsaugenklinik Göttingen Göttingen Germany
11 Universitätsaugenklinik Kiel Kiel Germany
12 Augenklinik TU München München Germany
13 Universitätsaugenklinik Regensburg Regensburg Germany

Sponsors and Collaborators

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

Investigators

  • Principal Investigator: Friederike Schaub, PD. Dr., Department of Ophthalmology, University of Cologne

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Universitätsklinikum Köln
ClinicalTrials.gov Identifier:
NCT02834559
Other Study ID Numbers:
  • uni-koeln-1782
  • 2015-004731-12
First Posted:
Jul 15, 2016
Last Update Posted:
Apr 5, 2022
Last Verified:
Apr 1, 2022

Study Results

No Results Posted as of Apr 5, 2022