A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00336323
First received: June 9, 2006
Last updated: July 28, 2011
Last verified: July 2011
Results First Received: March 16, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetic Retinopathy
Interventions: Procedure: Laser Photocoagulation
Drug: Bevacizumab

  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
Thirty-six clinical sites across the United States recruited 121 subjects (109 met criteria for inclusion in the analyses) between June 2006 and August 2006.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Unless otherwise noted, differences in number of Participants at different visits reflect a missed visit, not a drop-out.

Reporting Groups
  Description
Laser at Baseline Laser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart
1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)
1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks

Participant Flow:   Overall Study
    Laser at Baseline     1.25 mg Injection at Baseline and at 6 Weeks     2.5 mg Injection at Baseline and 6 Weeks     1.25 mg Injection at Baseline Only     1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w  
STARTED     19     22     24     22     22  
3 Week Visit     18     21     24     22     20 [1]
6 Week Visit     18     22     24     22     20 [2]
9 Week Visit     18     21     23     21     19  
12 Week Visit     19     21     24     22     20 [3]
18 Week Visit     19     22     23     21     18 [4]
24 Week Visit     18     20 [4]   22 [4]   22     19  
COMPLETED     19     21     23     22     19  
NOT COMPLETED     0     1     1     0     3  
[1] Laser given late at six weeks for one patient
[2] 1 patient was dropped - injection was given late at 9 wks for one patient
[3] 1 patient was dropped from study
[4] 1 patient was dropped from the study



  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.
No text entered.

Reporting Groups
  Description
Laser at Baseline Laser photocoagulation at baseline: If edema is present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart
1.25 mg Injection at Baseline and at 6 Weeks 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
2.5 mg Injection at Baseline and 6 Weeks 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
1.25 mg Injection at Baseline Only 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)
1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
Total Total of all reporting groups

Baseline Measures
    Laser at Baseline     1.25 mg Injection at Baseline and at 6 Weeks     2.5 mg Injection at Baseline and 6 Weeks     1.25 mg Injection at Baseline Only     1.25 mg Injection at Baseline, Laser at 3w + 1.25 mg Inj at 3w     Total  
Number of Participants  
[units: participants]
  19     22     24     22     22     109  
Age  
[units: years]
Median ( Inter-Quartile Range )
  64  
  ( 57 to 72 )  
  63  
  ( 54 to 73 )  
  68  
  ( 59 to 75 )  
  60  
  ( 54 to 75 )  
  67  
  ( 60 to 71 )  
  65  
  ( 57 to 73 )  
Gender  
[units: participants]
           
Female     9     6     9     9     10     43  
Male     10     16     15     13     12     66  
Race/Ethnicity, Customized  
[units: participants]
           
White     10     16     20     18     19     83  
African-American     7     3     2     3     2     17  
Hispanic or Latino     2     2     2     0     1     7  
Asian     0     0     0     1     0     1  
Unknown/ not reported     0     1     0     0     0     1  
Character of Diabetic Macular Edema (DME) [1]
[units: participants]
           
Typical/Predominantly Focal     6     5     2     3     4     20  
Neither Predominantly Focal or Diffuse     4     5     5     6     6     26  
Typical/Predominantly Diffuse     9     12     17     13     12     63  
Cystoid Abnormalities on Optical Coherence Tomography (OCT)  
[units: participants]
           
Yes     18     22     24     21     21     106  
No     1     0     0     1     1     3  
Diabetes Type  
[units: participants]
           
Type 1     1     1     3     2     1     8  
Type 2     18     21     21     20     21     101  
Lens status (clinical examination)  
[units: participants]
           
Phakic     12     15     14     12     13     66  
Pseudophakic     7     7     10     10     9     43  
Prior Panretinal Scatter Photocoagulation  
[units: participants]
           
Yes     3     2     3     1     4     13  
No     16     20     21     21     18     96  
Prior Treatment for Diabetic Macular Edema (DME) in Study Eye  
[units: participants]
           
None     7     5     10     5     7     34  
Focal photocoagulation alone     4     11     9     6     9     39  
Focal photocoagulation plus other treatment     8     3     3     11     6     31  
Other treatment without focal photocoagulation     0     3     2     0     0     5  
Retinopathy Severity [2]
[units: participants]
           
Mild nonproliferative diabetic retinopathy (NPDR)     1     6     3     0     4     14  
Moderate NPDR     5     3     1     3     3     15  
Moderately severe NPDR     5     6     8     8     9     36  
Severe NPDR     0     1     2     4     1     8  
Mild proliferative diabetic retinopathy (PDR)     4     5     6     5     4     24  
Moderate PDR     1     0     2     0     1     4  
High Risk PDR     2     0     0     0     0     2  
Missing     1     1     2     2     0     6  
Subretinal Fluid on Optical Coherence Tomography (OCT)  
[units: participants]
           
Definite, center     2     2     7     2     4     17  
Definite, not center     0     1     1     0     1     3  
Questionable     0     1     0     2     0     3  
No evidence     16     18     16     18     17     85  
Missing     1     0     0     0     0     1  
Baseline Visual Acuity [3]
[units: letter score]
Median ( Inter-Quartile Range )
  64  
  ( 50 to 70 )  
  65  
  ( 60 to 70 )  
  63  
  ( 57 to 71 )  
  64  
  ( 52 to 68 )  
  66  
  ( 57 to 72 )  
  64  
  ( 56 to 71 )  
Duaration of Diabetes  
[units: years]
Median ( Inter-Quartile Range )
  17  
  ( 13 to 22 )  
  15  
  ( 8 to 22 )  
  18  
  ( 12 to 22 )  
  17  
  ( 11 to 25 )  
  20  
  ( 7 to 30 )  
  17  
  ( 11 to 23 )  
Hemoglobin A1c [4]
[units: percent HbA1c]
Median ( Inter-Quartile Range )
  7.0  
  ( 6.5 to 8.2 )  
  7.4  
  ( 5.9 to 7.8 )  
  7.3  
  ( 6.4 to 8.4 )  
  6.7  
  ( 6.3 to 7.4 )  
  7.1  
  ( 6.2 to 7.7 )  
  6.9  
  ( 6.3 to 8.1 )  
Optical Coherence Tomography (OCT) Central Subfield Thickness  
[units: microns]
Median ( Inter-Quartile Range )
  441  
  ( 354 to 512 )  
  397  
  ( 320 to 538 )  
  446  
  ( 342 to 543 )  
  406  
  ( 353 to 520 )  
  389  
  ( 308 to 452 )  
  411  
  ( 334 to 505 )  
Optical Coherence Tomography Retinal Volume  
[units: mm^3]
Median ( Inter-Quartile Range )
  8.3  
  ( 7.3 to 10.2 )  
  9.5  
  ( 8.0 to 10.3 )  
  9.1  
  ( 8.0 to 10.0 )  
  8.9  
  ( 7.7 to 10.0 )  
  8.6  
  ( 7.7 to 9.2 )  
  8.6  
  ( 7.8 to 10.1 )  
[1] Criteria used to define categories was based on investigator discretion.
[2] Early Treatment Diabetic Retinopathy Study Severity Scale
[3] 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.
[4] Missing for 8 patients



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits   [ Time Frame: Baseline to 3,6,9, and 12 weeks ]

2.  Primary:   Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits   [ Time Frame: Baseline to 3,6,9, and 12 Weeks ]

3.  Secondary:   Change in Visual Acuity Letter Score From Baseline Over All All Study Visits   [ Time Frame: Baseline to 3,6,9, and 12 weeks ]

4.  Secondary:   Distribution of Change in Visual Acuity Over All Study Visits   [ Time Frame: Baseline to 3,6,9, and 12 weeks ]

5.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Central Subfield Thickness   [ Time Frame: Baseline to 3 Weeks ]

6.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Baseline Visual Acuity Letter Score   [ Time Frame: Baseline to 3 Weeks ]

7.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline   [ Time Frame: Baseline to 3 Weeks ]

8.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Gender   [ Time Frame: Baseline to 3 Weeks ]

9.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema at Baseline   [ Time Frame: Baseline to 3 Weeks ]

10.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline   [ Time Frame: baseline to 3 Weeks ]

11.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline   [ Time Frame: baseline to 3 Weeks ]

12.  Other Pre-specified:   Change in Central Subfield Thickness in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline   [ Time Frame: baseline to 3 Weeks ]

13.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Central Subfield Thickness at Baseline   [ Time Frame: baseline to 3 Weeks ]

14.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Visual Acuity at Baseline   [ Time Frame: baseline to 3 Weeks ]

15.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Age at Baseline   [ Time Frame: baseline to 3 Weeks ]

16.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Gender   [ Time Frame: baseline to 3 Weeks ]

17.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to History of Treatment for Diabetic Macular Edema   [ Time Frame: baseline to 3 Weeks ]

18.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Retinopathy Severity at Baseline   [ Time Frame: baseline to 3 Weeks ]

19.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Clinical Diabetic Macular Edema Characterization at Baseline   [ Time Frame: baseline to 3 Weeks ]

20.  Other Pre-specified:   Change in Visual Acuity (Letters) in Bevacizumab Groups From Baseline to 3 Weeks According to Subretinal Fluid Presence at Baseline   [ Time Frame: baseline to 3 Weeks ]

21.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

22.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had Within a ±11% Change of Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

23.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Injection Only and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

24.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Decrease in Change of Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

25.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had Within a ±11% Change in Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

26.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab and Had a >11% Increase in Change of Central Subfield Thickness From Baseline to 3 Weeks   [ Time Frame: 3 to 6 Weeks ]

27.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]

28.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]

29.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 1.25mg Bevacizumab at 6 Weeks and Had a >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]

30.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had a >11% Decrease in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]

31.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within ±11% Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]

32.  Other Pre-specified:   Change in Central Subfield Thickness From 3 to 6 Weeks Among Eyes That Received 2.5mg Bevacizumab at 6 Weeks and Had Within >11% Increase in Change of Central Subfield Thickness From 6 Weeks to 9 Weeks   [ Time Frame: 3 to 9 weeks ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Name/Official Title: Adam Glassman, M.S., Director
Organization: Jaeb Center for Health Research, Diabetic Retinopathy Clinical Research Network
phone: (813) 975-8690
e-mail: drcrnet@jaeb.org


Publications of Results:
Publications automatically indexed to this study:

Responsible Party: Roy W. Beck, M.D., Ph.D., Director, Jaeb Center for Health Research (DRCR.net)
ClinicalTrials.gov Identifier: NCT00336323     History of Changes
Other Study ID Numbers: NEI-129, U10EY018817-03, U10EY014229-07, U10EY014231-09, EY14231, EY14269, EY14229
Study First Received: June 9, 2006
Results First Received: March 16, 2011
Last Updated: July 28, 2011
Health Authority: United States: Food and Drug Administration