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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
First received
Last updated
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
Health authority
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.

Study Design


Related Conditions & MeSH terms


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
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