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

Primary Purpose

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

Status
Completed
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
5-fluorouracil and low molecular weight heparin
Placebo
Sponsored by
Universitätsklinikum Köln
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rhegmatogenous Retinal Detachment

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Augenklinik Uniklinik Freiburg
  • STZ eyetrial am Department für Augenheilkunde
  • Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf
  • Augenklinik Uniklinik Bonn
  • Universitäts-Augenklinik Düsseldorf
  • Augenklinik der Universität zu Köln
  • Augenärzte am St. Franziskushospital Münster Augenklinik
  • Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach
  • Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde
  • Universitätsaugenklinik Göttingen
  • Universitätsaugenklinik Kiel
  • Augenklinik TU München
  • Universitätsaugenklinik Regensburg

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Adjuvant therapy with 5-FU and LMWH

Standard of care

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
July 12, 2016
Last Updated
April 4, 2022
Sponsor
Universitätsklinikum Köln
Collaborators
German Research Foundation, The Clinical Trials Centre Cologne, Pharmacy of the University Hospital Erlangen, Institute of Medical Statistics, Informatics and Epidemiology (IMSIE)
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1. Study Identification

Unique Protocol Identification Number
NCT02834559
Brief Title
Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.
Acronym
PRIVENT
Official Title
Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent PVR in High-risk Patients With Retinal Detachment.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 27, 2016 (Actual)
Primary Completion Date
June 15, 2020 (Actual)
Study Completion Date
June 15, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Köln
Collaborators
German Research Foundation, The Clinical Trials Centre Cologne, Pharmacy of the University Hospital Erlangen, Institute of Medical Statistics, Informatics and Epidemiology (IMSIE)

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rhegmatogenous Retinal Detachment, High-risk for Proliferative Vitreoretinopathy (PVR)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
326 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Adjuvant therapy with 5-FU and LMWH
Arm Type
Active Comparator
Arm Description
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).
Arm Title
Standard of care
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil and low molecular weight heparin
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Routinely used intraocular infusion with balanced salt solution (BSS) during routine pars plana vitrectomy (PPV).
Primary Outcome Measure Information:
Title
Proliferative Vitreoretinopathy (PVR) grade CP (posterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]
Time Frame
within 12 weeks
Secondary Outcome Measure Information:
Title
PVR grade CP 1 or higher [yes/no]
Time Frame
within 6 weeks
Title
PVR grade CA (anterior - full thickness retinal folds in clock hours) 1 or higher [yes/no]
Time Frame
within 6 weeks and 12 weeks
Title
Degree of PVR (PVR grade CA 1-12, PVR grade CP 1-12 (in clock hours))
Time Frame
within 6 weeks and 12 weeks
Title
Best Corrected Visual Acuity (BCVA) measured by ETDRS charts
Time Frame
within 6 weeks and 12 weeks
Title
Retinal reattachment after primary intervention [yes/no]
Time Frame
within 6 weeks and 12 weeks
Title
Number of retinal re-detachments and if present due to PVR [yes/no]
Time Frame
within 6 weeks and 12 weeks
Title
Number and extent of surgical procedures necessary to achieve retinal reattachment
Time Frame
within 12 weeks
Title
Occurrence of at least one drug-related adverse event that affects the study eye [yes/no]
Time Frame
within 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Primary rhegmatogenous retinal detachment (< 4 weeks) in study eye Scheduled for pars plana vitrectomy for retinal detachment repair without combined cataract surgery in study eye Elevated protein levels in anterior chamber fluid (laser-flare value ≥ 15.0 pc/ms) in study eye Female or male patient ≥ 18 years of age Written informed consent Exclusion Criteria: Retinal detachment lasting > 4 weeks in study eye Traumatic retinal detachment in study eye Giant retinal tears in study eye (size > 3 clock hours) Visual pre-existing PVR grade C in study eye Retinal dystrophies in study eye Scheduled for combined pars plana vitrectomy and cataract surgery for retinal detachment repair in study eye Chronic inflammatory conditions in study eye Active retinal vascular disease in study eye Proliferative diabetic retinopathy in study eye Manifest uveitis in study eye Endophthalmitis in study eye Perforating and non-perforating trauma in study eye Malignant intraocular tumor in study eye Aphakia in study eye Uncontrolled glaucoma or ocular hypertension in study eye (intraocular pressure ≥ 30 mmHg despite IOP lowering therapy) Previous intraocular surgery except uncomplicated cataract surgery with posterior chamber lens implantation in study eye Cataract surgery in study eye ≤ 3 months ago Previous retinal procedures (laserpexy, cryopexy, intravitreal gas-injection, anti-VEGF or corticosteroid-injection) in study eye ≤ 6 months Other uncontrolled ophthalmologic disorders Single eyed patients (BCVA of fellow eye > 1.0 log MAR, < 0.1 decimal, < 1/10 tenth, or < 6/60 Snellen fraction [m]) Evidence or history of alcohol, medication or drug dependency within the last 12 months. Evidence or history (within the last 12 months) of neurotic personality, psychiatric illness that requires or required treatment, epilepsy or suicide risk. Systemic disorders not compatible with adjuvant application of 5-FU and LMWH via intraocular infusion, or not compatible with the local or general anesthesia Any therapy with immunosuppressant or chemotherapy ≤ 3 months and during the trial period Participation in another trial of IMPs or devices parallel to, or less than 3 months before screening, or previous participation in this trial. Known to or suspected of not being able to comply with the protocol. Inability to understand the rationale of this trial or the study aim 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. Positive urine pregnancy test, pregnancy or breastfeeding mother. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Friederike Schaub, PD. Dr.
Organizational Affiliation
Department of Ophthalmology, University of Cologne
Official's Role
Principal Investigator
Facility Information:
Facility Name
Augenklinik Uniklinik Freiburg
City
Freiburg
State/Province
BW
ZIP/Postal Code
79106
Country
Germany
Facility Name
STZ eyetrial am Department für Augenheilkunde
City
Tübingen
State/Province
BW
ZIP/Postal Code
72076
Country
Germany
Facility Name
Klinik und Poliklinik für Augenheilkunde Uniklinik Hamburg Eppendorf
City
Hamburg
State/Province
HH
ZIP/Postal Code
20246
Country
Germany
Facility Name
Augenklinik Uniklinik Bonn
City
Bonn
State/Province
NRW
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitäts-Augenklinik Düsseldorf
City
Dusseldorf
State/Province
NRW
ZIP/Postal Code
40255
Country
Germany
Facility Name
Augenklinik der Universität zu Köln
City
Koln
State/Province
NRW
ZIP/Postal Code
50931
Country
Germany
Facility Name
Augenärzte am St. Franziskushospital Münster Augenklinik
City
Munster
State/Province
NRW
ZIP/Postal Code
48145
Country
Germany
Facility Name
Knappschaftskrankenhaus Sulzbach Augenklinik Sulzbach
City
Sulzbach
State/Province
Saarbrücken
ZIP/Postal Code
66280
Country
Germany
Facility Name
Uniklinik Leipzig Klinik und Poliklinik für Augenheilkunde
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitätsaugenklinik Göttingen
City
Göttingen
Country
Germany
Facility Name
Universitätsaugenklinik Kiel
City
Kiel
Country
Germany
Facility Name
Augenklinik TU München
City
München
Country
Germany
Facility Name
Universitätsaugenklinik Regensburg
City
Regensburg
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
30012187
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.
Results Reference
derived

Learn more about this trial

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

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