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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00336323
First Posted: June 13, 2006
Last Update Posted: August 26, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Eye Institute (NEI)
Information provided by:
Jaeb Center for Health Research
Results First Submitted: March 16, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetic Retinopathy
Interventions: Procedure: Laser Photocoagulation
Drug: Bevacizumab

  Participant Flow
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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 
[1] Criteria used to define categories was based on investigator discretion.
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 [1] 
[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 
[1] Early Treatment Diabetic Retinopathy Study Severity Scale
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 [1] 
[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) 
[1] 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.
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 [1] 
[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) 
[1] Missing for 8 patients
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) 


  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


  Limitations and Caveats
  Hide 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.


  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.


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 by ClinicalTrials.gov Identifier (NCT Number):

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 ( U.S. NIH Grant/Contract )
U10EY014229-07 ( U.S. NIH Grant/Contract )
U10EY014231-09 ( U.S. NIH Grant/Contract )
EY14231, EY14269, EY14229
First Submitted: June 9, 2006
First Posted: June 13, 2006
Results First Submitted: March 16, 2011
Results First Posted: July 12, 2011
Last Update Posted: August 26, 2016