Anti-VEGF vs. Prompt Vitrectomy for VH From PDR

NCT ID: NCT02858076

Last Updated: 2021-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 205 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2020-01-31

Brief 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.

Detailed Description

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

Conditions

Proliferative Diabetic Retinopathy; Vitreous Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intravitreous 2 mg aflibercept injections

Initial injection must be given on the day of randomization. Follow-up injections will be performed as often as every 4 weeks unless criteria for deferral are met.

Group Type: ACTIVE_COMPARATOR

2-mg Intravitreous Aflibercept Injection

Intervention Type: DRUG

Soluble decoy receptor fusion protein that has a high binding affinity to all isoforms of VEGF as well as to placental growth factor.

Prompt vitrectomy plus panretinal photocoagulation

For the prompt vitrectomy + panretinal photocoagulation group, the vitrectomy must be scheduled to be performed within 2 weeks of randomization. Vitrectomy will be performed according to the investigator's usual routine, including pre-operative care, surgical procedure, and post-operative care, although anti-VEGF may not be given post-operatively unless there is recurrent hemorrhage.

Group Type: ACTIVE_COMPARATOR

Prompt Vitrectomy Plus Panretinal Photocoagulation

Intervention Type: PROCEDURE

Surgical removal of the vitreous gel and associated hemorrhage, concurrent delivery of panretinal endolaser

Interventions

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.

Intervention Type: DRUG

Prompt Vitrectomy Plus Panretinal Photocoagulation

Surgical removal of the vitreous gel and associated hemorrhage, concurrent delivery of panretinal endolaser

Intervention Type: PROCEDURE

Other Intervention Names

Eylea; Vascular endothelial growth factor Trap-Eye; PRP

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Antoszyk, MD

Role: STUDY_CHAIR

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Locations

Retinal Diagnostic Center

Campbell, California, United States

Macula & Retina Institute

Glendale, California, United States

Atlantis Eye Care

Huntington Beach, California, United States

Loma Linda University Health Care, Department of Ophthalmology

Loma Linda, California, United States

Shashi D Ganti, MD PC

Porterville, California, United States

Florida Retina Consultants

Lakeland, Florida, United States

Southeast Eye Institute, P.A. dba Eye Associates of Pinellas

Pinellas Park, Florida, United States

Retina Associates of Sarasota

Sarasota, Florida, United States

Retina Associates of Florida, P.A.

Tampa, Florida, United States

Emory Eye Center

Atlanta, Georgia, United States

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Marietta Eye Clinic

Marietta, Georgia, United States

Thomas Eye Group

Sandy Springs, Georgia, United States

Gailey Eye Clinic

Bloomington, Illinois, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

Carle Foundation Hospital

Urbana, Illinois, United States

Raj K. Maturi, MD, PC

Indianapolis, Indiana, United States

John-Kenyon American Eye Institute

New Albany, Indiana, United States

Retina Associates, P.A.

Shawnee Mission, Kansas, United States

Paducah Retinal Center

Paducah, Kentucky, United States

Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

West Monroe, Louisiana, United States

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Valley Eye Physicians and Surgeons

Ayer, Massachusetts, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

Detroit, Michigan, United States

Retina Specialists of Michigan

Grand Rapids, Michigan, United States

Retina Center, PA

Minneapolis, Minnesota, United States

Mayo Clinic Department of Ophthalmology

Rochester, Minnesota, United States

Mid-America Retina Consultants, P.A.

Kansas City, Missouri, United States

The Retina Institute

St Louis, Missouri, United States

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, United States

MaculaCare

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

Kittner Eye Center

Chapel Hill, North Carolina, United States

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Charlotte, North Carolina, United States

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Retina Vitreous Center

Edmond, Oklahoma, United States

Dean A. McGee Eye Institute

Oklahoma City, Oklahoma, United States

Oregon Retina, LLP

Eugene, Oregon, United States

Retina Northwest, PC

Portland, Oregon, United States

Casey Eye Institute

Portland, Oregon, United States

Retina Vitreous Consultants

Monroeville, Pennsylvania, United States

Palmetto Retina Center

West Columbia, South Carolina, United States

Southeastern Retina Associates

Chattanooga, Tennessee, United States

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

Southwest Retina Specialists

Amarillo, Texas, United States

Retina Research Center

Austin, Texas, United States

Retina and Vitreous of Texas

Houston, Texas, United States

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Texas Retina Associates

Lubbock, Texas, United States

Valley Retina Institute

McAllen, Texas, United States

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Spokane Eye Clinic

Spokane, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

UBC/VCHA Eye Care Centre

Vancouver, British Columbia, Canada

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Beaulieu WT, Maguire MG, Antoszyk AN; DRCR Retina Network. Changes in activity impairment and work productivity after treatment for vitreous hemorrhage due to proliferative diabetic retinopathy: Secondary outcomes from a randomized controlled trial (DRCR Retina Network Protocol AB). PLoS One. 2023 Nov 16;18(11):e0293543. doi: 10.1371/journal.pone.0293543. eCollection 2023.

Reference Type: DERIVED

PMID: 37972038 (View on PubMed)

Glassman AR, Beaulieu WT, Maguire MG, Antoszyk AN, Chow CC, Elman MJ, Jampol LM, Salehi-Had H, Sun JK; DRCR Retina Network. Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2021 Jul 1;139(7):725-733. doi: 10.1001/jamaophthalmol.2021.1110.

Reference Type: DERIVED

PMID: 33956075 (View on PubMed)

Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, Salehi-Had H, Wells JA 3rd, Maguire MG, Stockdale CR, Martin DF, Sun JK; DRCR Retina Network. Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2020 Dec 15;324(23):2383-2395. doi: 10.1001/jama.2020.23027.

Reference Type: DERIVED

PMID: 33320223 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

EY14231

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EY23207

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EY18817

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DRCR.net Protocol AB

Identifier Type: -

Identifier Source: org_study_id