Transcript Deferred PRP Group - Jaeb Center for Health Research

The 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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Background
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 Groups
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 noninferior 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.)
Prompt PRP
0.5mg
ranibizumab
with deferred
PRP
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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 outcomes
Perform cost effectiveness analysis
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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 Criteria
Age ≥ 18 years
Type 1 or 2 diabetes
PDR for which PRP is planned but in the
investigator’s opinion can be deferred
for at least 4 weeks if an intravitreal antiVEGF injection is given
Visual acuity (Snellen equivalent) 20/320
or better
Note: eyes with or without DME may be
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enrolled
Major 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 – Undilated
within 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 – Undilated
Day 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 - 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 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 Schedule
Baseline to
1 Year
• 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
1 Year to
3 Years
• 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
4 to 5
Years
• Annual visits for data collection only
• Treatment as part of usual care
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Non-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
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(except in OU participants)
Annual 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)
 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)
 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 examined
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Injection Retreatment Criteria for PDR
(Deferred PRP Group)
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
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Injection Retreatment Criteria for PDR
(Deferred PRP Group)
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 examined
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Injection Retreatment Criteria for PDR
(Deferred PRP Group)
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)
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.
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Follow-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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