The Diabetic Retinopathy Clinical Research Network DRCR.net Prompt PRP vs Ranibizumab+Deferred PRP...
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Transcript of The Diabetic Retinopathy Clinical Research Network DRCR.net Prompt PRP vs Ranibizumab+Deferred PRP...
![Page 1: The Diabetic Retinopathy Clinical Research Network DRCR.net Prompt PRP vs Ranibizumab+Deferred PRP for PDR Study Jeffrey G. Gross, M.D. – Protocol Chair.](https://reader036.fdocuments.in/reader036/viewer/2022062304/56649e375503460f94b26ec3/html5/thumbnails/1.jpg)
The Diabetic Retinopathy Clinical Research NetworkThe Diabetic Retinopathy
Clinical Research Network
DRCR.net Prompt PRP vs Ranibizumab+Deferred PRP for
PDR Study
Jeffrey G. Gross, M.D. – Protocol Chair
Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and
Human Services EY14231, EY14229, EY018817
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BackgroundBackground
Current treatment for PDR is panretinal photocoagulation (PRP)• Inherently destructive• Adverse effects on visual function
Some eyes with PDR+DME now receive anti-VEGF as standard care for DME
Would initial treatment of PDR with intravitreal anti-VEGF delay or prevent need for PRP?
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Study Objective and Treatment GroupsStudy Objective and Treatment Groups
Prompt PRP
To determine if visual acuity outcomes at 2 years in eyes with PDR (with or without concurrent DME) that receive anti-VEGF therapy with deferred PRP are non-
inferior to those in eyes that receive prompt PRP therapy.
(Note: Study ranibizumab may be given as needed for DME using Protocol I retreatment as guidelines.)
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0.5mg ranibizumab with deferred
PRP
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Important Secondary Objectives(assuming visual acuity outcomes are non-inferior)Important Secondary Objectives(assuming visual acuity outcomes are non-inferior)
Compare visual function outcomes (including Humphrey visual field testing and study participant self-reports of visual function)
Determine percent of eyes not requiring PRP when intravitreal anti-VEGF is given in the absence of prompt PRP
Compare safety outcomesPerform cost effectiveness analysis
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Sample Size Sample Size
Minimum of 380 eyes
Subjects may have one or two study eyes
316 participants assuming 20% have two study eyes
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Major Inclusion CriteriaMajor Inclusion CriteriaAge ≥ 18 yearsType 1 or 2 diabetesPDR for which PRP is planned but in the
investigator’s opinion can be deferred for at least 4 weeks if an intravitreal anti-VEGF injection is given
Visual acuity (Snellen equivalent) 20/320 or better
Note: eyes with or without DME may be enrolled 6
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Major Exclusion CriteriaMajor Exclusion Criteria
Systemic• Significant renal disease• BP > 180/110• Cardiac event or stroke within 4 months
Study eye• Prior PRP• Tractional retinal detachment involving the macula• NV of the angle• History of intravitreal anti-VEGF within past 2 months• History of corticosteriod in the past 4 months
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Testing Procedures – Undilatedwithin 14 days of randomization
Testing Procedures – Undilatedwithin 14 days of randomization
Questionnaires (except in participants with two study eyes)• NEI-VFQ, UAB-LLQ, WPAI, and TTO
Humphrey visual field testing (30-2 and 60-4) – dilation may be needed depending on pupil size• Required at sites with certified HVF equipment
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Testing Procedures – UndilatedDay of Randomization
Testing Procedures – UndilatedDay of Randomization
E-ETDRS best-corrected visual acuity in each eye
Binocular E-ETDRS using the participant’s everyday glasses or contacts
IOP in the study eye
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Testing Procedures - DilatedTesting Procedures - Dilated
OCT of study eye (within 8 days) Fundus photographs of study eye (within 21
days)• If NV is not captured on 7F or 4W, additional fields
should be taken to capture NV• This is documented on protocol specific form
Ocular exam in both eyes (day of randomization)
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PRP TreatmentPRP Treatment
Prompt PRP group receives 1200 to 1600 burns initiated on day of randomization (or within 14 days of baseline if injection for DME given) and completed within 8 weeks.
Anti-VEGF+Deferred PRP may receive PRP only if failure/futility criteria are met • Protocol chair approval MUST be obtained
before PRP is given in some cases of failure/futility
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Follow-up ScheduleFollow-up Schedule
Baseline to 1 Year
1 Year to 3 Years
• Assessment Visits every 16 weeks in both groups
• PDR Treatment Visits every 4 weeks (deferred PRP group only)…interval may only be extended if PRP is given
• Assessment Visits every 16 weeks in both groups
• PDR Treatment Visit every 4-16w (deferred PRP group only)…interval is extended if injections for PDR continually deferred
• Primary outcome visit at 2 years
• Annual visits for data collection only• Treatment as part of usual care
4 to 5Years
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Non-Annual Testing ProceduresNon-Annual Testing Procedures E-ETDRS best-corrected visual acuity in both eyes Ocular exam and IOP in the study eye (extended
ophthalmoscopy in deferred PRP group) OCT only if eye
• 1) has initiated DME treatment, • 2) will be evaluated for initial DME treatment, or • 3)10 letter unexplained loss since last visit.
Fundus photography only if PRP will be initiated in an eye assigned to IVR+deferred PRP
WPAI questionnaire at 16-week interval visits (except in OU participants)
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Annual Testing ProceduresAnnual Testing Procedures
Binocular E-ETDRS using the participant’s everyday glasses or contacts
Questionnaires (except in OU participants)• NEI-VFQ, UAB-LLQ, WPAI, and TTO• May be completed at home prior to visit (within 14
days)
Fundus photography Humphrey visual field testing (30-2 and 60-4)• Required at sites with certified HVF equipment
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Anti-VEGF Injections for PDR (Deferred PRP Group)
Anti-VEGF Injections for PDR (Deferred PRP Group)
Injections every 4 weeks through 12- week visit• NV status does not matter• Injection can only be skipped if an adverse event
occurs
If at anytime the investigator thinks PRP is needed within 1 week to avoid substantial vision loss, PRP may be given once protocol chair approval obtained
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Injection Retreatment Criteria for PDR (Deferred PRP Group)
Injection Retreatment Criteria for PDR (Deferred PRP Group)
Starting at the 16-week visit, each eye will be categorized into one of the following 5 groups:
1. Resolved NV of the retina, disc, and iris/angle* is absent. Decision to re-inject is at investigator
discretion. PRP should not be given.
*if angle is examined16
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2. Improved NV of the retina, disc, or iris/angle* still
persists, but there is evidence of “improvement” since the last visit.
“Improvement” defined as a decrease in the size of NV or diminished density of NV
An injection is given. PRP should not be given.
*if angle is examined 17
Injection Retreatment Criteria for PDR (Deferred PRP Group)
Injection Retreatment Criteria for PDR (Deferred PRP Group)
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3. Stable NV of the retina, disc, and iris/angle* is
clinically unchanged since the last visit. Once the eye meets criteria for stability, at
least 2 more injections must be given, each one month apart. Further reinjection is then at investigator discretion as long as the eye remains stable. PRP should not be given.
*if angle is examined18
Injection Retreatment Criteria for PDR (Deferred PRP Group)
Injection Retreatment Criteria for PDR (Deferred PRP Group)
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4. Not fully treated Failure/futility criteria not met and recurrent or
worsening NV of the retina, disc, or iris is present in an eye that has had fewer than 4 injections over the previous 4 months or there is vitreous or preretinal hemorrhage precluding assessment.
An injection is given. PRP should not be given.
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Injection Retreatment Criteria for PDR (Deferred PRP Group)
Injection Retreatment Criteria for PDR (Deferred PRP Group)
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5. Failure/futility One of the following criteria are met:
• NV worse than last visit such that it is greater in extent than baseline and at least 4 injections given over previous 4 months• NV of the angle• PRP needed within 1 week to avoid substantial
vision loss and protocol chair approval obtained• Persistent NV after 1.5 years of follow-up despite
anti-VEGF and protocol chair approval obtained
Decision to re-inject is at investigator discretion. PRP may be given. 20
Injection Retreatment Criteria for PDR (Deferred PRP Group)
Injection Retreatment Criteria for PDR (Deferred PRP Group)
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Follow-Up Treatment for DMEFollow-Up Treatment for DME
If DME develops during follow-up, treatment is at investigator discretion using study ranibizumab and/or focal/grid laser with Protocol I retreatment criteria as guidelines
Additional follow-up visits for DME retreatment are at the discretion of the investigator (not part of visit schedule)
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