Clinical trial NCT02858076: Anti-VEGF vs. Prompt Vitrectomy for VH From PDR
Official title: Intravitreous Anti-VEGF vs. Prompt Vitrectomy for Vitreous Hemorrhage From Proliferative Diabetic Retinopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Proliferative Diabetic Retinopathy
Vitreous Hemorrhage
Keywords: Anti-VEGF
Vitrectomy
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Regeneron Pharmaceuticals
name: National Eye Institute (NEI)
First posted: 2016-08-08
Enrollment: 205
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

* 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.

Primary outcomes:
measure: E-ETDRS Visual Acuity Letter Score (Area Under the Curve From Baseline)
timeFrame: 24 weeks
Secondary outcomes:
measure: E-ETDRS Visual Acuity Letter Score
timeFrame: 4 Weeks
measure: E-ETDRS Visual Acuity Letter Score
timeFrame: 12 Weeks
measure: E-ETDRS Visual Acuity Letter Score
timeFrame: 24 Weeks
measure: E-ETDRS Visual Acuity Letter Score
timeFrame: 1-Year from participant randomization
measure: E-ETDRS Visual Acuity Letter Score
timeFrame: 2 Years
measure: E-ETDRS Visual Acuity Letter Score (Area Under the Curve From Baseline)
timeFrame: 2-Years
measure: Snellen Equivalent Range (Visual Acuity Score)
timeFrame: 4 weeks
measure: Snellen Equivalent Range (Visual Acuity Score)
timeFrame: 12 weeks
measure: Snellen Equivalent Range (Visual Acuity Score)
timeFrame: 24 weeks
measure: Snellen Equivalent Range (Visual Acuity Score)
timeFrame: 1 year
measure: Snellen Equivalent Range (Visual Acuity Score)
timeFrame: 2 years
measure: Recurrent Vitreous Hemorrhage
timeFrame: At any time through 2 years
measure: Retinal Neovascularization on Clinical Exam
timeFrame: 24 weeks
measure: Retinal Neovascularization on Clinical Exam
timeFrame: 1 year
measure: Retinal Neovascularization on Clinical Exam
timeFrame: 2 years
Other outcomes:
Locations:
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Glendale
country: United States
facility: Macula & Retina Institute
state: California
city: Huntington Beach
country: United States
facility: Atlantis Eye Care
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Department of Ophthalmology
state: California
city: Porterville
country: United States
facility: Shashi D Ganti, MD PC
state: California
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Pinellas Park
country: United States
facility: Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
state: Florida
city: Sarasota
country: United States
facility: Retina Associates of Sarasota
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida, P.A.
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Augusta
country: United States
facility: Southeast Retina Center, P.C.
state: Georgia
city: Marietta
country: United States
facility: Marietta Eye Clinic
state: Georgia
city: Sandy Springs
country: United States
facility: Thomas Eye Group
state: Georgia
city: Bloomington
country: United States
facility: Gailey Eye Clinic
state: Illinois
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Hospital
state: Illinois
city: Indianapolis
country: United States
facility: Raj K. Maturi, MD, PC
state: Indiana
city: New Albany
country: United States
facility: John-Kenyon American Eye Institute
state: Indiana
city: Shawnee Mission
country: United States
facility: Retina Associates, P.A.
state: Kansas
city: Paducah
country: United States
facility: Paducah Retinal Center
state: Kentucky
city: West Monroe
country: United States
facility: Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
state: Louisiana
city: Baltimore
country: United States
facility: Elman Retina Group, P.A.
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute at Johns Hopkins
state: Maryland
city: Ayer
country: United States
facility: Valley Eye Physicians and Surgeons
state: Massachusetts
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
state: Michigan
city: Grand Rapids
country: United States
facility: Retina Specialists of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Retina Center, PA
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Department of Ophthalmology
state: Minnesota
city: Kansas City
country: United States
facility: Mid-America Retina Consultants, P.A.
state: Missouri
city: Saint Louis
country: United States
facility: The Retina Institute
state: Missouri
city: New York
country: United States
facility: The New York Eye and Ear Infirmary/Faculty Eye Practice
state: New York
city: New York
country: United States
facility: MaculaCare
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Syracuse
country: United States
facility: Retina-Vitreous Surgeons of Central New York, PC
state: New York
city: Chapel Hill
country: United States
facility: Kittner Eye Center
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye, Ear, Nose and Throat Assoc., PA
state: North Carolina
city: Beachwood
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Edmond
country: United States
facility: Retina Vitreous Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute
state: Oklahoma
city: Eugene
country: United States
facility: Oregon Retina, LLP
state: Oregon
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Monroeville
country: United States
facility: Retina Vitreous Consultants
state: Pennsylvania
city: West Columbia
country: United States
facility: Palmetto Retina Center
state: South Carolina
city: Chattanooga
country: United States
facility: Southeastern Retina Associates
state: Tennessee
city: Knoxville
country: United States
facility: Southeastern Retina Associates, P.C.
state: Tennessee
city: Amarillo
country: United States
facility: Southwest Retina Specialists
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina and Vitreous of Texas
state: Texas
city: Houston
country: United States
facility: Baylor Eye Physicians and Surgeons
state: Texas
city: Lubbock
country: United States
facility: Texas Retina Associates
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: Spokane
country: United States
facility: Spokane Eye Clinic
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: UBC/VCHA Eye Care Centre
state: British Columbia
city: Toronto
country: Canada
facility: University Health Network - Toronto Western Hospital
state: Ontario
Study officials:
affiliation: Charlotte Eye, Ear, Nose and Throat Assoc., PA
name: Andrew Antoszyk, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.