Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema (LRT for DME)

This study has been completed.
Sponsor:
Collaborators:
Allergan
Genentech
Information provided by (Responsible Party):
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00444600
First received: March 6, 2007
Last updated: April 7, 2014
Last verified: April 2014
Results First Received: January 14, 2011  
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: Diabetic Retinopathy
Diabetic Macular Edema
Interventions: Drug: Triamcinolone Acetonide + laser
Drug: Ranibizumab + laser
Drug: Sham injection + laser
Drug: Ranibizumab + deferred laser

  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
Fifty two academic and community based sites across the United States recruited 691 study participants from March 2007 to December 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with two study eyes enrolled each eye in a different treatment group. Therefore, each treatment group/arm includes no more than one 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+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Participant Flow:   Overall Study
    Sham+Prompt Laser     0.5 mg Ranibizumab+Prompt Laser     0.5 mg Ranibizumab+Deferred Laser     4 mg Triamcinolone+Prompt Laser  
STARTED     293 [1]   187 [1]   188 [1]   186 [1]
COMPLETED     274 [1]   171 [1]   178 [1]   176 [1]
NOT COMPLETED     19     16     10     10  
Death                 7                 5                 3                 2  
Dropped                 11                 11                 7                 7  
Missed visit                 1                 0                 0                 1  
[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.
No text entered.

Reporting Groups
  Description
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.
Total Total of all reporting groups

Baseline Measures
    Sham+Prompt Laser     0.5 mg Ranibizumab+Prompt Laser     0.5 mg Ranibizumab+Deferred Laser     4 mg Triamcinolone+Prompt Laser     Total  
Number of Participants  
[units: participants]
  293     187     188     186     854  
Age  
[units: years]
Median ( Inter-Quartile Range )
  63  
  ( 57 to 69 )  
  62  
  ( 56 to 70 )  
  64  
  ( 58 to 70 )  
  62  
  ( 55 to 70 )  
  63  
  ( 56 to 70 )  
Gender  
[units: participants]
         
Female     123     85     78     86     372  
Male     170     102     110     100     482  
Race/Ethnicity, Customized  
[units: Participants]
         
White     202     131     134     134     601  
African American     51     30     25     32     138  
Hispanic or Latino     34     21     25     15     95  
Asian     4     1     2     4     11  
Native Hawaiian/Other Pacific Islander     0     1     0     0     1  
More than one race     1     1     1     0     3  
Unknown/not reported     1     2     1     1     5  
Visual Acuity Letter Score (approximate Snellen equivalent) by randomization strata  
[units: Eyes]
         
≥66 (better than 20/50)     146     95     95     93     429  
≤65 (20/50 or worse)     147     92     93     93     425  
Classification of diabetic macular edema [1]
[units: Eyes]
         
Predominantly focal     78     60     68     53     259  
Neither predominantly focal or diffuse     71     46     41     48     206  
Predominantly diffuse     144     81     79     85     389  
Number of study eyes  
[units: Participants]
         
1 study eye     130     131     132     135     528  
2 study eyes     163     56     56     51     326  
Diabetes Type  
[units: Participants]
         
Type 1     25     11     15     14     65  
Type 2     260     172     170     166     768  
Uncertain     8     4     3     6     21  
Duration of diabetes  
[units: Years]
Median ( Inter-Quartile Range )
  16  
  ( 9 to 22 )  
  18  
  ( 12 to 24 )  
  17  
  ( 11 to 22 )  
  17  
  ( 11 to 24 )  
  16  
  ( 10 to 23 )  
HbA1c [2]
[units: Percentage]
Median ( Inter-Quartile Range )
  7.3  
  ( 6.6 to 8.3 )  
  7.3  
  ( 6.6 to 8.4 )  
  7.5  
  ( 6.7 to 8.4 )  
  7.4  
  ( 6.5 to 8.6 )  
  7.3  
  ( 6.6 to 8.4 )  
Prior cardiovascular event [3]
[units: Participants]
         
Yes     93     66     61     61     281  
No     200     121     127     125     573  
Hypertension  
[units: Participants]
         
Yes     240     154     156     148     698  
No     53     33     32     38     156  
Prior Panretinal Photocoagulation  
[units: Eyes]
         
Yes     48     36     31     37     152  
No     245     151     157     149     702  
Prior treatment for diabetic macular edema  
[units: Eyes]
         
No     105     74     74     61     314  
Yes     188     113     114     125     540  
Prior laser for diabetic macular edema  
[units: Eyes]
         
Yes     173     101     101     114     489  
No     120     86     87     72     365  
Prior IVT for diabetic macular edema [4]
[units: Eyes]
         
Yes     39     22     36     31     128  
No     254     165     152     155     726  
Prior vitrectomy for diabetic macular edema  
[units: Eyes]
         
Yes     15     7     5     12     39  
No     278     180     183     174     815  
Prior peribulbar triamcinolone for diabetic macular edema  
[units: Eyes]
         
Yes     12     9     5     5     31  
No     281     178     183     181     823  
Prior anti-VEGF for diabetic macular edema [5]
[units: Eyes]
         
Yes     24     24     21     20     89  
No     269     163     167     166     765  
Intraocular pressure  
[units: mmHg]
Median ( Inter-Quartile Range )
  16  
  ( 14 to 18 )  
  16  
  ( 14 to 18 )  
  16  
  ( 14 to 18 )  
  16  
  ( 14 to 18 )  
  16  
  ( 14 to 18 )  
Currently on intraocular pressure lowering medicine for glaucoma or ocular hypertension  
[units: Eyes]
         
Yes     5     6     4     2     17  
No     288     181     184     184     837  
Lens status [1]
[units: Eyes]
         
Phakic     192     131     134     124     581  
Anterior Chamber Intraocular Lense     3     1     1     0     5  
Posterior Chamber Intraocular Lense     98     55     53     62     268  
E-ETDRS Visual Acuity Letter Score [6]
[units: LetterĀ Score]
Median ( Inter-Quartile Range )
  65  
  ( 56 to 73 )  
  66  
  ( 55 to 72 )  
  66  
  ( 58 to 72 )  
  66  
  ( 57 to 72 )  
  66  
  ( 56 to 72 )  
Central subfield thickness on optical coherence tomography  
[units: microns]
Median ( Inter-Quartile Range )
  407  
  ( 309 to 505 )  
  371  
  ( 302 to 464 )  
  382  
  ( 298 to 488 )  
  374  
  ( 298 to 463 )  
  381  
  ( 306 to 485 )  
Retinal volume on optical coherence tomography  
[units: microns]
Median ( Inter-Quartile Range )
  8.7  
  ( 7.8 to 10.0 )  
  8.4  
  ( 7.5 to 9.6 )  
  8.4  
  ( 7.4 to 9.8 )  
  8.5  
  ( 7.8 to 9.7 )  
  8.5  
  ( 7.7 to 9.7 )  
Optical coherence tomography cystoid abnormality  
[units: Eyes]
         
No evidence     19     13     12     8     52  
Questionable or definite     274     171     174     177     796  
Cannot grade or missing     0     3     2     1     6  
Optical coherence tomography subretinal fluid present  
[units: Eyes]
         
No evidence     222     149     140     146     657  
Questionable or definite     70     36     45     38     189  
Cannot grade     1     2     3     2     8  
ETDRS retinopathy severity level (ETDRS description) [7]
[units: Eyes]
         
Diabetic retinopathy absent     5     4     3     1     13  
Minimal non-proliferative DR     2     2     3     3     10  
Mild to moderately severe non-proliferative DR     171     103     107     95     476  
Severe non-proliferative DR     22     16     11     15     64  
Scars of full or partial PRP present;PDR absent     38     30     30     29     127  
Mild to moderate proliferative DR     33     24     22     34     113  
High risk proliferative DR     7     4     1     3     15  
Cannot grade     10     1     2     4     17  
Missing     5     3     9     2     19  
[1] Based on clinical exam.
[2] Missing HbA1c data for 17, 3, 7 and 8 study participants in the sham+prompt laser, ranibizumab+prompt laser, ranibizumab+deferred laser and triamcinolone+prompt laser groups, respectively.
[3] Based on medical history of condition.
[4] IVT = intravitreal triamcinolone
[5] VEGF = vascular endothelial growth factor
[6] 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.
[7]

ETDRS = Early Treatment Diabetic Retinopathy Study; DR = diabetic retinopathy; PDR = proliferative diabetic retinopathy.

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
  Show All Outcome Measures

1.  Primary:   Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity   [ Time Frame: from baseline to 1 Year ]

2.  Primary:   Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year   [ Time Frame: from baseline to 1 Year ]

3.  Primary:   Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline   [ Time Frame: from baseline to 1 Year ]
  Hide Outcome Measure 3

Measure Type Primary
Measure Title Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline
Measure Description No text entered.
Time Frame from baseline to 1 Year  
Safety Issue No  

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
Sham+Prompt Laser Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Prompt Laser 0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.
0.5 mg Ranibizumab+Deferred Laser 0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.
4 mg Triamcinolone+Prompt Laser 4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Measured Values
    Sham+Prompt Laser     0.5 mg Ranibizumab+Prompt Laser     0.5 mg Ranibizumab+Deferred Laser     4 mg Triamcinolone+Prompt Laser  
Number of Participants Analyzed  
[units: participants]
  293     187     188     186  
Number of Eyes Analyzed  
[units: Eyes]
  293     187     188     186  
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline  
[units: Letters]
Mean ± Standard Deviation
       
Not pseudophakic at baseline     2  ± 13     9  ± 10     10  ± 14     2  ± 14  
Pseudophakic at baseline     4  ± 14     8  ± 12     7  ± 9     8  ± 9  

No statistical analysis provided for Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline



4.  Primary:   Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema   [ Time Frame: from baseline to 1 Year ]

5.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score   [ Time Frame: from baseline to 1 Year ]

6.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness   [ Time Frame: from baseline to 1 Year ]

7.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity   [ Time Frame: from baseline to 1 Year ]

8.  Primary:   Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator   [ Time Frame: from baseline to 1 Year ]

9.  Secondary:   Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year   [ Time Frame: from baseline to 1 year ]

10.  Secondary:   Number of Injections in First Year   [ Time Frame: from baseline to 1 year ]

11.  Secondary:   Number of Laser Treatments Received Prior to the 1 Year Visit   [ Time Frame: 1 Year ]

12.  Secondary:   Percentage of Eyes Receiving Laser at the 48 Week Visit (%)   [ Time Frame: 1 Year ]

13.  Secondary:   Mean Optical Coherence Tomography Retinal Volume at 1 Year   [ Time Frame: 1 Year ]

14.  Secondary:   Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year   [ Time Frame: from baseline to 1 Year ]

15.  Other Pre-specified:   Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year   [ Time Frame: 1 Year ]

16.  Other Pre-specified:   Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening   [ Time Frame: 1 Year ]

17.  Other Pre-specified:   Eyes With Alternative Treatments Prior to the 1-year Visit   [ Time Frame: 1 Year ]

18.  Other Pre-specified:   Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year   [ Time Frame: from baseline to 1 Year ]

19.  Other Pre-specified:   Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year   [ Time Frame: from baseline to 1 Year ]

20.  Other Pre-specified:   Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year   [ Time Frame: 1 Year ]

21.  Other Pre-specified:   Major Ocular Adverse Events During First Year of Follow-Up   [ Time Frame: 1 Year ]


  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.


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