Anti-VEGF vs. Prompt Vitrectomy for VH From PDR

Proliferative Diabetic Retinopathy Clinical Trial

— AB  

Official title:

Intravitreous Anti-VEGF vs. Prompt Vitrectomy for Vitreous Hemorrhage From Proliferative Diabetic Retinopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02858076
• Other study ID #: DRCR.net Protocol AB
• Secondary ID: EY14231EY23207EY
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 2016
• Est. completion date: January 2020

Study information

• Verified date: February 2021
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although vitreous hemorrhage (VH) from proliferative diabetic retinopathy (PDR) can cause acute and dramatic vision loss for patients with diabetes, there is no current, evidence-based clinical guidance as to what treatment method is most likely to provide the best visual outcomes once intervention is desired. Intravitreous anti-vascular endothelial growth factor (anti-VEGF) therapy alone or vitrectomy combined with intraoperative PRP each provide the opportunity to stabilize or regress retinal neovascularization. However, clinical trials are lacking to elucidate the relative time frame of visual recovery or final visual outcome in prompt vitrectomy compared with initial anti-VEGF treatment. The Diabetic Retinopathy Clinical Research Network Protocol N demonstrated short-term trends consistent with a possible beneficial effect of anti-VEGF treatment in eyes with VH from PDR, including greater visual acuity improvement and reduced rates of recurrent VH as compared with saline injection. It is possible that a study with a longer duration of follow-up with structured anti-VEGF retreatment would demonstrate even greater effectiveness of anti-VEGF for VH to avoid vitrectomy and its attendant adverse events while also improving visual acuity. On the other hand, advances in surgical techniques leading to faster operative times, quicker patient recovery, and reduced complication rates may make prompt vitrectomy a more attractive alternative since it results in the immediate ability to clear hemorrhage and to perform PRP if desired, often as part of one procedure. This proposed study will evaluate the safety and efficacy of two treatment approaches for eyes with VH from PDR: prompt vitrectomy + PRP and intravitreous aflibercept injections.

Description:

A participant could have only one eye enrolled in the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 205
• Est. completion date: January 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >= 18 years Participants <18 years old are not being included because proliferative diabetic retinopathy is so rare in this age group that the diagnosis may be questionable.

2. Diagnosis of diabetes mellitus (type 1 or type 2)

Any one of the following will be considered to be sufficient evidence that diabetes is present:

• Current regular use of insulin for the treatment of diabetes

• Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes

• Documented diabetes by American Diabetes Association and/or World Health Organization criteria 4. Able and willing to provide informed consent. 5. Patient is willing and able to undergo vitrectomy within next 2 weeks and the vitrectomy can be scheduled within that time frame.

6. Vitreous hemorrhage causing vision impairment, presumed to be from proliferative diabetic retinopathy, for which intervention is deemed necessary.

• Note: Prior panretinal photocoagulation is neither a requirement nor an exclusion.

• Subhyaloid hemorrhage alone does not make an eye eligible; however, presence of subhyaloid hemorrhage in addition to the criteria above will not preclude participation provided the investigator is comfortable with either treatment regimen.

7. Immediate vitrectomy not required (investigator and participant are willing to wait at least 4 months to see if hemorrhage clears sufficiently with anti-vascular endothelial growth factor without having to proceed to vitrectomy).

8. Visual acuity letter score =78 (approximate Snellen equivalent 20/32) and at least light perception.

9. Investigators should use particular caution when considering enrollment of an eye with visual acuity letter score 69 to 78 (approximate Snellen equivalent 20/32 to 20/40) to ensure that the need for vitrectomy and its potential benefits outweigh the potential risks.

Exclusion Criteria:

• A potential participant is not eligible if any of the following exclusion criteria are present:

1. History of chronic renal failure requiring dialysis (including placement of fistula if performed in preparation for dialysis) or kidney transplant.

2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

3. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.

4. A condition that, in the opinion of the investigator, would preclude participant undergoing elective vitrectomy surgery if indicated during the study.

5. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

• Note: participants cannot receive another investigational drug while participating in the study.

6. Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine).

7. Blood pressure > 180/110 (systolic above 180 or diastolic above 110).

8. If blood pressure is brought below 180/110 by anti-hypertensive treatment, potential participant can become eligible.

9. Systemic anti-vascular endothelial growth factor or pro-vascular endothelial growth factor treatment within 4 months prior to randomization.

• These drugs cannot be used during the study.

10. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next two years.

• Women who are potential participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.

11. Potential participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the two years.

12. Evidence of traction detachment involving or threatening the macula.

• If the density of the hemorrhage precludes a visual assessment on clinical exam to confirm eligibility, then it is recommended that assessment be performed with ultrasound as standard care.

13. Evidence of rhegmatogenous retinal detachment.

• If the density of the hemorrhage precludes a visual assessment on clinical exam to confirm eligibility, then it is recommended that assessment be performed with ultrasound as standard care.

14. Evidence of neovascular glaucoma (iris or angle neovascularization is not an exclusion).

15. Known diabetic macular edema (DME), defined as either

16. Optical coherence tomography central subfield thickness (microns):

17. Zeiss Cirrus: =290 in women; =305 in men

18. Heidelberg Spectralis: =305 in women; =320 in men OR

19. Diabetic macular edema on clinical exam that the investigator believes currently requires treatment.

20. History of intravitreous anti-vascular endothelial growth factor treatment within 2 months prior to current vitreous hemorrhage onset or after onset.

21. History of intraocular corticosteroid treatment within 4 months prior to current vitreous hemorrhage onset or after onset.

22. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery other than vitrectomy anticipated within the next 6 months following randomization.

23. History of vitrectomy.

24. History of YAG capsulotomy performed within 2 months prior to randomization.

25. Aphakia.

26. Uncontrolled glaucoma (in investigator's judgment).

27. Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis.

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Hemorrhage
• Proliferative Diabetic Retinopathy
• Retinal Diseases
• Vitreous Hemorrhage

Intervention

Drug:
• 2-mg Intravitreous Aflibercept Injection
Soluble decoy receptor fusion protein that has a high binding affinity to all isoforms of VEGF as well as to placental growth factor.

Procedure:
• Prompt Vitrectomy Plus Panretinal Photocoagulation
Surgical removal of the vitreous gel and associated hemorrhage, concurrent delivery of panretinal endolaser

Locations

Country	Name	City	State
Canada	University Health Network - Toronto Western Hospital	Toronto	Ontario
Canada	UBC/VCHA Eye Care Centre	Vancouver	British Columbia
United States	Southwest Retina Specialists	Amarillo	Texas
United States	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan
United States	Emory Eye Center	Atlanta	Georgia
United States	Southeast Retina Center, P.C.	Augusta	Georgia
United States	Retina Research Center	Austin	Texas
United States	Valley Eye Physicians and Surgeons	Ayer	Massachusetts
United States	Elman Retina Group, P.A.	Baltimore	Maryland
United States	Wilmer Eye Institute at Johns Hopkins	Baltimore	Maryland
United States	Retina Associates of Cleveland, Inc.	Beachwood	Ohio
United States	Gailey Eye Clinic	Bloomington	Illinois
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	Retinal Diagnostic Center	Campbell	California
United States	Kittner Eye Center	Chapel Hill	North Carolina
United States	Charlotte Eye, Ear, Nose and Throat Assoc., PA	Charlotte	North Carolina
United States	Southeastern Retina Associates	Chattanooga	Tennessee
United States	Northwestern Medical Faculty Foundation	Chicago	Illinois
United States	University of Illinois at Chicago Medical Center	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Henry Ford Health System, Dept of Ophthalmology and Eye Care Services	Detroit	Michigan
United States	Retina Vitreous Center	Edmond	Oklahoma
United States	Oregon Retina, LLP	Eugene	Oregon
United States	Macula & Retina Institute	Glendale	California
United States	Retina Specialists of Michigan	Grand Rapids	Michigan
United States	Baylor Eye Physicians and Surgeons	Houston	Texas
United States	Retina and Vitreous of Texas	Houston	Texas
United States	Atlantis Eye Care	Huntington Beach	California
United States	Raj K. Maturi, MD, PC	Indianapolis	Indiana
United States	Mid-America Retina Consultants, P.A.	Kansas City	Missouri
United States	Southeastern Retina Associates, P.C.	Knoxville	Tennessee
United States	Florida Retina Consultants	Lakeland	Florida
United States	Loma Linda University Health Care, Department of Ophthalmology	Loma Linda	California
United States	Texas Retina Associates	Lubbock	Texas
United States	Marietta Eye Clinic	Marietta	Georgia
United States	Valley Retina Institute	McAllen	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Retina Center, PA	Minneapolis	Minnesota
United States	Retina Vitreous Consultants	Monroeville	Pennsylvania
United States	John-Kenyon American Eye Institute	New Albany	Indiana
United States	MaculaCare	New York	New York
United States	The New York Eye and Ear Infirmary/Faculty Eye Practice	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Dean A. McGee Eye Institute	Oklahoma City	Oklahoma
United States	Paducah Retinal Center	Paducah	Kentucky
United States	Southeast Eye Institute, P.A. dba Eye Associates of Pinellas	Pinellas Park	Florida
United States	Shashi D Ganti, MD PC	Porterville	California
United States	Casey Eye Institute	Portland	Oregon
United States	Retina Northwest, PC	Portland	Oregon
United States	Mayo Clinic Department of Ophthalmology	Rochester	Minnesota
United States	The Retina Institute	Saint Louis	Missouri
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Thomas Eye Group	Sandy Springs	Georgia
United States	Retina Associates of Sarasota	Sarasota	Florida
United States	Retina Associates, P.A.	Shawnee Mission	Kansas
United States	Spokane Eye Clinic	Spokane	Washington
United States	Retina-Vitreous Surgeons of Central New York, PC	Syracuse	New York
United States	Retina Associates of Florida, P.A.	Tampa	Florida
United States	Carle Foundation Hospital	Urbana	Illinois
United States	Palmetto Retina Center	West Columbia	South Carolina
United States	Eye Associates of Northeast Louisiana dba Haik Humble Eye Center	West Monroe	Louisiana

Sponsors (4)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	National Eye Institute (NEI), National Institutes of Health (NIH), Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	E-ETDRS Visual Acuity Letter Score (Area Under the Curve From Baseline)	The area under the curve (units = letters·weeks) was divided by 24 weeks (units = weeks) to obtain an average change in letter score (units = letters) over the 24-weekr follow-up.; Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	24 weeks
Secondary	E-ETDRS Visual Acuity Letter Score	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	4 Weeks
Secondary	E-ETDRS Visual Acuity Letter Score	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	12 Weeks
Secondary	E-ETDRS Visual Acuity Letter Score	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	24 Weeks
Secondary	E-ETDRS Visual Acuity Letter Score	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	1-Year from participant randomization
Secondary	E-ETDRS Visual Acuity Letter Score	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	2 Years
Secondary	E-ETDRS Visual Acuity Letter Score (Area Under the Curve From Baseline)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity. The area under the curve (units = letters·years) was divided by 2 years (units = years) to obtain an average change in letter score (units = letters) over the 2-year follow-up.; Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent of <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	2-Years
Secondary	Snellen Equivalent Range (Visual Acuity Score)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	4 weeks
Secondary	Snellen Equivalent Range (Visual Acuity Score)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	12 weeks
Secondary	Snellen Equivalent Range (Visual Acuity Score)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	24 weeks
Secondary	Snellen Equivalent Range (Visual Acuity Score)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity.	1 year
Secondary	Snellen Equivalent Range (Visual Acuity Score)	Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/10) to 0 letters (Snellen equivalent <20/800). Higher scores indicate better visual acuity and lower scores indicate worse visual acuity..	2 years
Secondary	Recurrent Vitreous Hemorrhage	Assessed by the investigator and defined as presence of vitreous hemorrhage after a period of absence. Excludes eyes in which vitreous hemorrhage could not be assessed during follow-up.	At any time through 2 years
Secondary	Retinal Neovascularization on Clinical Exam	Defined as neovascularization of the disc or elsewhere. Excludes eyes in which retinal neovascularization could not be determined.	24 weeks
Secondary	Retinal Neovascularization on Clinical Exam	Defined as neovascularization of the disc or elsewhere. Excludes eyes in which retinal neovascularization could not be determined	1 year
Secondary	Retinal Neovascularization on Clinical Exam	Defined as neovascularization of the disc or elsewhere. Excludes eyes in which retinal neovascularization could not be determined	2 years