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

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

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.  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 ]