Download Protocol S Overview - 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.
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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Rationale for Combining Eyes
With and Without DME
 Eyes without DME at baseline may develop DME
during follow-up, requiring concurrent anti-VEGF
treatment anyway
 Treatment effect of Prompt vs Deferred PRP in
both cohorts is expected to be similar
 Logistically easier for sites compared with two
separate protocols
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Follow-up Schedule
Baseline to
1 Year
1 Year to
3 Years
4 to 5
Years
• Both groups: Visits every 16 weeks
• IVR+Deferred PRP group: Visits every 4
weeks to evaluate for ranibizumab…interval
may only be extended if PRP is given
• Both groups: Visits every 16 weeks
• IVR+Deferred PRP group: Visit every 4-16w
to evaluate for ranibizumab…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
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Study Procedures
PROCEDURE
Medical history
TIMING
Baseline only
E- ETDRS Visual Acuity
All visits
Binocular E-ETDRS VA
Annually only
Questionnaires (4)
HVF Testing (30-2 and 60-4)*
7MF or 4W Digital Photos
(+additional fields as needed)
OCT
Ocular Exam w/IOP
3 Annually; 1 q 16w
Annually only
Annually only + Prior to
PRP in Deferred Group
Annually + As Needed
for DME Evaluations
All visits
Blood Pressure
Baseline only
HbA1c
Baseline only
*Only at sites with HVF capabilities
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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
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Anti-VEGF Injections
for PDR (IVR+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
(IVR+Deferred PRP Group)
 Starting at the 16-week visit, each eye will be
categorized into one of the following 5 groups:
Category
Injection
PRP
Resolved
At investigator discretion
No
Improved
Required
Required 1st 2 times stable; then
at investigator discretion
No
Required
No
At investigator discretion
Yes
Stable
Not fully treated
(worsening)
Failure/Futility
No
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Treatment for DME
If DME present at baseline causing VA
loss, ranibizumab must be given
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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Referrals
 Please consider any eyes with proliferative
diabetic retinopathy that might normally be
treated with PRP
 Study participants must be willing to be
randomized to either group and continue followup for 5 years
 Consenting/Enrollment/Randomization may be
split into several visits
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Thank You on Behalf of Diabetic
Retinopathy Clinical Research Network
(DRCR.net)
Dedicated to multicenter clinical research of diabetic
retinopathy, macular edema and associated disorders.
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