Prompt Panretinal Photocoagulation Versus Ranibizumab+Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy (Protocol S)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Eye Institute (NEI)
Genentech, Inc.
Information provided by (Responsible Party):
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT01489189
First received: December 6, 2011
Last updated: June 1, 2016
Last verified: June 2016
Results First Received: February 12, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Proliferative Diabetic Retinopathy
Interventions: Other: Prompt Panretinal Photocoagulation
Drug: 0.5-mg Ranibizumab
Other: Deferred panretinal photocoagulation

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Participants with 2 eyes in the study had 1 eye randomly assigned to receive ranibizumab and 1 eye to receive panretinal photocoagulation.

Two-year completed visits include those that occurred between 644 and 812 days (between 92 and 116 weeks).


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Anti-VEGF+Deferred PRP

Anti vascular endothelial growth factor (Anti-VEGF). Panretinal photocoagulation (PRP). Intravitreal anti-VEGF with PRP only if indicated.

0.5-mg Ranibizumab: Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.

Deferred panretinal photocoagulation: PRP is deferred until failure/futility criteria for intravitreal injection are met.

Prompt PRP

Panretinal Photocoagulation (PRP). PRP alone.

Prompt Panretinal Photocoagulation: Panretinal photocoagulation alone at baseline (full session completed within 56 days).


Participant Flow:   Overall Study
    Anti-VEGF+Deferred PRP     Prompt PRP  
STARTED     191 [1]   203 [1]
COMPLETED     160 [1]   168 [1]
NOT COMPLETED     31     35  
Withdrawal by Subject                 20                 23  
Death                 10                 8  
Missed Visit                 1                 4  
[1] Number of Eyes



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Units in Eyes

Reporting Groups
  Description
Anti-VEGF+Deferred PRP

Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.

0.5-mg Ranibizumab: Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.

Deferred panretinal photocoagulation: PRP is deferred until failure/futility criteria for intravitreal injection are met.

Prompt PRP

PRP= Panretinal Photocoagulation. PRP alone.

Prompt Panretinal Photocoagulation: Panretinal photocoagulation alone at baseline (full session completed within 56 days).

Total Total of all reporting groups

Baseline Measures
    Anti-VEGF+Deferred PRP     Prompt PRP     Total  
Number of Participants  
[units: participants]
  191     203     394  
Age, Customized  
[units: years]
Median (Inter-Quartile Range)
  52  
  (44 to 59)  
  51  
  (44 to 59)  
  51  
  (44 to 59)  
Gender, Customized  
[units: eyes]
     
Female     83     92     175  
Male     108     111     219  
Race/Ethnicity, Customized  
[units: eyes]
     
White     100     101     201  
Hispanic     48     51     99  
Black/African American     38     43     81  
Asian     2     3     5  
American Indian/Alaskan Native     1     0     1  
More than 1 race     0     2     2  
Unknown/not reported     2     3     5  
Number of study eyes  
[units: eyes]
     
One     102     114     216  
Two (one in each group)     89     89     178  
Diabetes Type  
[units: eyes]
     
Type 1     43     41     84  
Type 2     140     155     295  
Uncertain     8     7     15  
Duration of Diabetes  
[units: years]
Median (Inter-Quartile Range)
  18  
  (12 to 24)  
  17  
  (11 to 23)  
  18  
  (11 to 24)  
Hemoglobin A1c [1]
[units: percent]
Median (Inter-Quartile Range)
  8.6  
  (7.5 to 10.4)  
  8.9  
  (7.5 to 10.4)  
  8.7  
  (7.5 to 10.4)  
Prior Myocardial Infarction  
[units: eyes]
  3     4     7  
Prior Stroke  
[units: eyes]
  4     3     7  
Arterial Blood Pressure  
[units: mmHg]
Median (Inter-Quartile Range)
  99  
  (88 to 108)  
  99  
  (88 to 107)  
  99  
  (88 to 108)  
Visual Acuity [2]
[units: letters]
Mean (Standard Deviation)
  75  (12.8)     75.2  (12.5)     75.1  (12.6)  
Optical Coherence Tomography Central Subfield Thickness [3]
[units: µm]
Median (Inter-Quartile Range)
  223  
  (196 to 271)  
  230  
  (203 to 265)  
  229  
  (199 to 266)  
Presence of Center-Involved Diabetic Macular Edema with Visual Acuity Impairment [4]
[units: eyes]
  42     46     88  
Presence of Center-Involved Diabetic Macular Edema Regardless of Visual Acuity [4]
[units: eyes]
  55     62     117  
Neovascularization on Clinical Examination  
[units: eyes]
     
Of the disc     96     103     199  
Elsewhere     166     174     340  
Phakic Lens Status on Clinical Exam  
[units: eyes]
  170     187     357  
Diabetic Retinopathy Severity [5]
[units: eyes]
     
Microaneurysms only (level 20)     0     1     1  
Mild NPDR (level 35)     6     4     10  
Moderate NPDR (level 43)     2     5     7  
Moderately severe NPDR (level 47)     10     15     25  
Severe NPDR (level 53)     1     1     2  
Prior PRP without active PDR (level 60)     0     1     1  
Mild PDR (level 61)     30     31     61  
Moderate PDR (level 65)     68     67     135  
High-risk PDR (levels 71 and 75)     69     73     142  
Advanced PDR, macular center attached (level 81)     2     0     2  
Advanced PDR, macular center detached (level 85)     1     1     2  
Prior treatment for diabetic macular edema (DME)  
[units: eyes]
  43     36     79  
Prior focal/grid laser treatment for DME  
[units: eyes]
  30     29     59  
Prior anti-VEGF treatment for DME  
[units: eyes]
  21     13     34  
[1] Hemoglobin A1c data were missing for 7 in the anti-VEGF+Deferred PRP group and 5 in the prompt PRP group.
[2] Best corrected visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. Best value on the scale 97, worst 0.
[3]

OCT central subfield thickness measurements were missing for 2 in the anti-VEGF+deferred PRP group and 2 in the prompt PRP group.

Assessments from OCT machines other than Zeiss Stratus were converted to equivalent on Zeiss Stratus machines.

[4] OCT central subfield thickness measurements were missing for 2 in the anti-VEGF+deferred PRP group and 2 in the Prompt PRP group.
[5] Diabetic retinopathy level data were missing for 2 in the anti-VEGF+deferred PRP group and 4 in the prompt PRP group. Proliferative diabetic retinopathy (PDR) could not be identified by the reading center in 46 eyes (12%) but was subsequently confirmed by other imaging modes in 29 (63%) of the 46 eyes.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Mean Change in Visual Acuity From Baseline   [ Time Frame: 2-years ]

2.  Secondary:   Mean Visual Acuity   [ Time Frame: 2-years ]

3.  Secondary:   Number of Eyes With Greater Than or Equal to 10 Letter Vision Gain   [ Time Frame: 2-years ]

4.  Secondary:   Humphrey Visual Field Test Cumulative Score Change From Baseline   [ Time Frame: 2-years ]

5.  Secondary:   Frequency of Vitrectomy   [ Time Frame: 2-years ]

6.  Secondary:   Mean Change in OCT Central Subfield Thickness From Baseline   [ Time Frame: 2-years ]

7.  Secondary:   Development of Central DME With Vision Impairment by 2-years   [ Time Frame: 2-years ]

8.  Secondary:   Number of Eyes With Vitreous Hemorrhage   [ Time Frame: 2-years ]

9.  Secondary:   Number of Eyes Without Active or Regressed Neovascularization on Fundus Photography at 2-years   [ Time Frame: 2-years ]

10.  Secondary:   Number of Eyes With Greater Than or Equal to 10 Letter Vision Loss   [ Time Frame: 2-year ]

11.  Secondary:   Treatment and Follow-up Costs   [ Time Frame: 2-years ]
Results not yet reported.   Anticipated Reporting Date:   08/2016   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Adam Glassman
Organization: Jaeb Center for Health Research
phone: 813-975-8690
e-mail: drcrnet@jaeb.org


Publications of Results:

Responsible Party: Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier: NCT01489189     History of Changes
Other Study ID Numbers: DRCR.net Protocol S
Study First Received: December 6, 2011
Results First Received: February 12, 2016
Last Updated: June 1, 2016
Health Authority: United States: Federal Government