Laser-Ranibizumab-Triamcinolone for Proliferative Diabetic Retinopathy - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	Proliferative Diabetic Retinopathy Diabetic Macular Edema
Interventions:	Drug: Ranibizumab Drug: Triamcinolone Acetonide Behavioral: Sham injection Procedure: Focal/grid laser

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Data from 1 clinical site where a majority of eyes were judged not to meet the Optical Coherence Tomography eligibility criterion of central subfield >=250 microns when graded manually at a central reading center (14 eyes of 10 subjects) are excluded from all analysis except for safety data.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with 2 study eyes enrolled each eye in a different arm. Each treatment arm includes no more than 1 study eye for a given participant, and thus the numbers of eyes is equal to the number of participants in each arm.

Reporting Groups

	Description
Sham Injection	Sham injection at baseline and 4 weeks
0.5mg Ranibizumab	Intravitreal injections of 0.5mg Ranibizumab at baseline and at 4 weeks
4-mg Triamcinolone Acetonided	4-mg Triamcinolone Acetonide at baseline and sham injection at 4 weeks

Participant Flow: Overall Study

	Sham Injection	0.5mg Ranibizumab	4-mg Triamcinolone Acetonided
STARTED	123	113	109
COMPLETED	118	103	105
NOT COMPLETED	5	10	4
Death	1	2	1
Missed Visit	3	5	1
Dropped	1	3	2

Baseline Characteristics

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Reporting Groups

	Description
Sham Injection	Sham injection at baseline and 4 weeks
0.5mg Ranibizumab	Intravitreal injections of 0.5mg Ranibizumab at baseline and at 4 weeks
4-mg Triamcinolone Acetonided	4-mg Triamcinolone Acetonide at baseline and sham injection at 4 weeks

Baseline Measures

	Sham Injection	0.5mg Ranibizumab	4-mg Triamcinolone Acetonided	Total
Number of Participants [units: participants]	123	113	109	345
Age, Customized [units: years] Median ( Inter-Quartile Range )	54 ( 45 to 61 )	57 ( 48 to 64 )	58 ( 49 to 64 )	56 ( 45 to 64 )
Gender [units: participants]
Female	44	48	44	136
Male	79	65	65	209
Race/Ethnicity, Customized [units: participants]
American Indian or Alaska Native	1	0	1	2
Asian	3	1	2	6
Native Hawaiian or Other Pacific Islander	0	1	0	1
Black or African American	11	15	18	44
White	76	72	61	209
More than one race	0	0	0	0
Unknown or Not Reported	1	1	0	2
Hispanic or Latino	31	23	27	81
Optical coherence tomography subretinal fluid present (questionable or definite) ^[1] [units: Eyes]
Yes	30	31	32	93
No	93	82	77	252
Classification of diabetic macular edema on clinical exam [units: Eyes]
Predominantly Focal`	37	19	27	83
Neither perdominantly focal or diffuse	18	25	14	57
Predominantly diffuse	68	69	68	205
Intraocular Pressure [units: mmHg] Median ( Inter-Quartile Range )	15 ( 13 to 18 )	16 ( 14 to 18 )	15 ( 13 to 18 )	15 ( 13 to 18 )
Diabetes Type [units: Participants]
Type 1	20	13	12	45
Type 2	101	93	95	289
Uncertain	2	7	2	11
Duration of diabetes [units: Years] Median ( Inter-Quartile Range )	15 ( 8 to 21 )	15 ( 10 to 21 )	15 ( 10 to 19 )	15 ( 8 to 21 )
Hemoglobin A1c ^[2] [units: Percentage] Median ( Inter-Quartile Range )	7.9 ( 7.0 to 9.6 )	8.1 ( 7.1 to 9.9 )	8.1 ( 7.0 to 9.7 )	8.0 ( 7.0 to 9.9 )
Prior Cardiovascular event [units: Participants]
Yes	21	35	28	84
No	102	78	81	261
Hypertension [units: Participants]
Yes	97	88	82	267
No	26	25	27	78
Number of study eyes [units: Participants]
1 study eye	97	100	96	293
2 study eyes	26	13	13	52
Prior Panretinal scatter photocoagulation [units: Eyes]
Yes	16	20	19	55
No	107	93	90	290
prior treatment for diabetic macular edema [units: Eyes]
Yes	80	75	72	227
No	43	38	37	118
Prior laser for diabetic macular edema [units: Eyes]
Yes	40	33	36	109
No	83	80	73	236
Prior intravitreal triamcinolone for diabetic macular edema [units: Eyes]
Yes	1	9	3	13
No	122	104	106	332
Prior vitrectomy for diabetic macular edema [units: Eyes]
Yes	2	0	0	2
No	121	113	109	343
Prior peribulbar triamcinolone for diabetic macular edema [units: Eyes]
Yes	1	0	1	2
No	122	113	108	343
prior anti- vascular endothelial growth factor for diabetic macular edema [units: Eyes]
Yes	6	1	3	10
No	117	112	106	335
Currently on intraocular pressure lowering medication for glaucoma or ocular hypertension [units: Eyes]
Yes	0	3	0	3
No	123	110	109	342
Lens status (clinical examination) [units: Eyes]
Phakic	111	91	99	301
Pseudophakic	12	22	10	44
Baseline visual acuity by randomization strata ^[3] [units: Letter Score] Median ( Inter-Quartile Range )	67 ( 52 to 75 )	68 ( 56 to 75 )	67 ( 59 to 75 )	67 ( 52 to 75 )
Central subfield thickness on optical coherence tomography [units: Microns] Median ( Inter-Quartile Range )	355 ( 285 to 510 )	352 ( 283 to 476 )	359 ( 271 to 472 )	355 ( 283 to 510 )
Retinal volume on optical coherence tomography [units: cubic millimetre] Median ( Inter-Quartile Range )	9.4 ( 8.4 to 10.6 )	9.2 ( 8.3 to 11.0 )	9.1 ( 8.1 to 10.0 )	9.2 ( 8.1 to 11 )
Optical coherence tomography cystoid abnormality (questionable or definite) ^[4] [units: Eyes]
Yes	108	96	96	300
No	15	17	13	45
Early Treatment Diabetic Retinopath Study Retinopathy severity level from photograph grading ^[5] [units: Eyes]
Level 35, 43 (Mild/Moderate NPDR)	6	5	6	17
Level 47 (Moderately severe NPDR)	26	15	10	51
Level 53 (Severe NPDR)	5	6	5	16
Level 60 (Prior PRP without active neovascularizat	2	4	3	9
Level 61 (Mild/Moderate PDR)	48	36	38	122
Level 71, 75 (High-risk PDR)	32	43	43	118
cannot grade	4	4	4	12

[1]	Based on standard reading center grading
[2]	Missing hemoglobin A1c data for study participants in the sham, ranibizumab, and triamcinolone, respectively: 4, 10, 7
[3]	Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
[4]	From reading center grading.
[5]	Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833

Outcome Measures

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1. Primary:

Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 14 Weeks [ Time Frame: baseline to 14 weeks ]

Show Outcome Measure 1

2. Secondary:

Additional Treatments for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ]

Show Outcome Measure 2

3. Secondary:

Change in Optical Coherence Tomography Central Subfield Thickness [ Time Frame: Baseline to 14 weeks ]

Show Outcome Measure 3

4. Secondary:

Total Optical Coherence Tomography Retinal Volume [ Time Frame: Baseline to 14-weeks ]

Show Outcome Measure 4

5. Secondary:

Change in Visual Acuity From Baseline [ Time Frame: baseline to 56-weeks ]

Show Outcome Measure 5

6. Secondary:

Eyes With Anti-vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ]

Show Outcome Measure 6

7. Secondary:

Number of Eyes With Additional Number of Treatments for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ]

Show Outcome Measure 7

8. Secondary:

Change in Optical Coherence Tomography Retinal Volume [ Time Frame: Baseline to 14 weeks ]

Show Outcome Measure 8

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI 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
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Results Point of Contact:

Name/Title: Adam R. Glassman, Director DRCR.net Coordinating Center
Organization: Jaeb Center for Health Research
phone: 813-975-8690
e-mail: aglassman@jaeb.org

No publications provided by Diabetic Retinopathy Clinical Research Network

Publications automatically indexed to this study:

Gangaputra S, Almukhtar T, Glassman AR, Aiello LP, Bressler N, Bressler SB, Danis RP, Davis MD; Diabetic Retinopathy Clinical Research Network. Comparison of film and digital fundus photographs in eyes of individuals with diabetes mellitus. Invest Ophthalmol Vis Sci. 2011 Aug 3;52(9):6168-73. Print 2011 Aug.

Responsible Party:	Adam R. Glassman, MS, DRCR.net Director, Jaeb Center for Health Research (DRCR.net)
ClinicalTrials.gov Identifier:	NCT00445003 History of Changes
Other Study ID Numbers:	NEI-134, U10EY018817-03, U10EY014229-07, U10EY014231-09
Study First Received:	March 6, 2007
Results First Received:	April 14, 2011
Last Updated:	July 28, 2011
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration