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Long-Term Efficacy & Safety of Aflibercept IVT for the Treatment of DME in Subjects Who Completed the VISTA-DME Trial

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ClinicalTrials.gov Identifier: NCT02299336
Recruitment Status : Completed
First Posted : November 24, 2014
Results First Posted : June 7, 2018
Last Update Posted : June 4, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Charles C Wykoff, PhD, MD, Greater Houston Retina Research

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetic Macular Edema
Interventions Drug: Aflibercept
Procedure: Focal Laser
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Period Title: Overall Study
Started 60
Completed 46
Not Completed 14
Reason Not Completed
Withdrawal by Subject             11
Adverse Event             1
Death             1
Lost to Follow-up             1
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants
62.3  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
29
  48.3%
Male
31
  51.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
American Indian or Alaska Native
0
   0.0%
Asian
5
   8.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
9
  15.0%
White
46
  76.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 60 participants
60
Glycated Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  Percent
Number Analyzed 60 participants
7.5  (1.1)
Duration of Diabetes  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants
18.6  (10.6)
Early Treatment Diabetic Retinopathy Study Best-Corrected Visual Acuity   [1] 
Mean (Standard Deviation)
Unit of measure:  Letters
Number Analyzed 60 participants
69.6  (13.4)
[1]
Measure Description: Participants were challenged with reading letters on lines of an eye chart (5 letters per line) in standardized lighting conditions. Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.
Central Retinal Thickness  
Mean (Standard Deviation)
Unit of measure:  Microns
Number Analyzed 60 participants
290  (88.8)
1.Primary Outcome
Title Mean Number of Intravitreal Aflibercept Injections for Subjects Who Were Enrolled and Completed the 3-year VISTA DME (VGFT-OD-1009) Trial
Hide Description Measured by evaluating mean number of injections required for subjects who were enrolled and completed the 3-year VISTA DME (VGFT-OD-1009) trial
Time Frame Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 46
Mean (Standard Error)
Unit of Measure: injections
9.5  (6.7)
2.Secondary Outcome
Title Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity From Baseline to Week 52 and Baseline to Week 104
Hide Description Evaluate the mean change over time in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity at week 52 from baseline and at week 104 from baseline. Participants were challenged with reading letters on lines of an eye chart (5 letters per line) in standardized lighting conditions. Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Mean (Standard Error)
Unit of Measure: letters
52 Weeks Number Analyzed 54 participants
0.61  (1.28)
104 Weeks Number Analyzed 46 participants
0.83  (1.66)
3.Secondary Outcome
Title Mean Number of Intravitreal Aflibercept Injections Before and After Receiving First Focal Laser Application.
Hide Description Measure the role of focal laser treatment (fluorescein angiography-guided, if applicable) in decreasing the treatment burden among subjects who require ongoing aflibercept treatment in the management of diabetic macular edema.
Time Frame Before First Focal Laser Treatment (FLT) at Week 12 or later; After First FLT at up to 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Only participants who were eligible for focal laser treatment were analyzed.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: Injections
Injections Before First Focal Laser 7.5  (3.7)
Injections After First Focal Laser 6.7  (4.2)
4.Secondary Outcome
Title Percentage of Subjects With Gain or Loss of 0 to 5 Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Letters From Baseline to Week 52 and Baseline to Week 104
Hide Description Evaluate the percentage of subjects with a gain or loss in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity letters in patients treated with aflibercept from baseline to week 52 and baseline to week 104
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Measure Type: Count of Participants
Unit of Measure: Participants
Week 52 Number Analyzed 54 participants
35
  64.8%
Week 104 Number Analyzed 46 participants
30
  65.2%
5.Secondary Outcome
Title Mean Change in Central Retinal Thickness From Baseline to Week 52 and Baseline to Week 104.
Hide Description Evaluate the mean change in central retinal thickness from baseline to week 52 and baseline to week 104 in patients treated with aflibercept.
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Mean (Standard Error)
Unit of Measure: Microns
Week 52 Number Analyzed 54 participants
-7  (8.6)
Week 104 Number Analyzed 46 participants
1  (11.53)
6.Secondary Outcome
Title Number of Subjects With no Clinically-relevant Diabetic Macular Edema (as Defined in the Protocol) on Spectral Domain Optical Coherence Tomography From Baseline to Week 52 and Baseline to Week 104.
Hide Description Evaluate the number of subjects with no clinically-relevant diabetic macular edema (as defined in the protocol) on spectral domain optical coherence tomography from baseline to week 52 and baseline to week 104 in patients treated with aflibercept.
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Measure Type: Count of Participants
Unit of Measure: Participants
Week 52 Number Analyzed 54 participants
39
  72.2%
Week 104 Number Analyzed 46 participants
29
  63.0%
7.Secondary Outcome
Title Number of Subjects With Stable, Worsened, or Improved Diabetic Retinopathy
Hide Description Number of subjects with stable, worsened, or improved diabetic retinopathy through 104 weeks.
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Measure Type: Count of Participants
Unit of Measure: Participants
Week 52 Number Analyzed 54 participants
Worsened Diabetic Retinopathy
5
   9.3%
Stable Diabetic Retinopathy
46
  85.2%
Improved Diabetic Retinopathy
3
   5.6%
Week 104 Number Analyzed 46 participants
Worsened Diabetic Retinopathy
15
  32.6%
Stable Diabetic Retinopathy
27
  58.7%
Improved Diabetic Retinopathy
4
   8.7%
8.Secondary Outcome
Title Number of Subjects That Receive Focal Laser Treatment.
Hide Description Number of subjects that receive focal laser treatment from baseline to week 52 and from baseline to week 104.
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Measure Type: Count of Participants
Unit of Measure: Participants
Week 52 Number Analyzed 54 participants
25
  46.3%
Week 104 Number Analyzed 46 participants
27
  58.7%
9.Secondary Outcome
Title Mean Change in Early Treatment Diabetic Retinopathy Study Best-corrected Visual Acuity Before and After Focal Laser Therapy
Hide Description Evaluation of the effect of laser on Early Treatment Diabetic Retinopathy Study best-corrected visual acuity outcomes. Participants were challenged with reading letters on lines of an eye chart (5 letters per line) in standardized lighting conditions. Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants receiving laser were included in analysis.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: letters
Before First FLT Number Analyzed 25 participants
0.4  (6.2)
After First FLT Number Analyzed 27 participants
0.3  (11.9)
10.Secondary Outcome
Title Mean Change in Central Retinal Thickness Before and After First Focal Laser Treatment
Hide Description Evaluate the mean change in central retinal thickness before and after first focal laser treatment in patients treated with pro re nata aflibercept.
Time Frame 104 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All participants were included in analysis. Due to participant attrition, missed visits, and variable follow-up intervals, the population analyzed at each time point is equal to or smaller than the population still enrolled at that time point.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 60
Mean (Standard Error)
Unit of Measure: microns
Before First FLT Number Analyzed 25 participants
-8.5  (52.6)
After First FLT Number Analyzed 27 participants
-6.8  (41.6)
11.Secondary Outcome
Title Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Past and Future Anti-VEGF Treatment Burden
Hide Description Mean number of injections in 52 weeks and 104 weeks based on quantification of ischemic areas
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was never performed because we were logistically unable to collect the data.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Visual Outcomes
Hide Description Mean change in visual acuity from baseline to week 52 and baseline to week 104 based on quantification of ischemic areas
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was never performed because we were logistically unable to collect the data.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Role of (Ultrawide-field, if Available) Fluorescein Angiography-determined Retinal Ischemia in Predicting Anatomic Outcomes
Hide Description Mean change in central retinal thickness from baseline to week 52 based on quantification of ischemic areas
Time Frame Week 52, Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis was never performed because we were logistically unable to collect the data.
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description:

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 104 weeks.
Adverse Event Reporting Description Adverse events were assessed at every study visit during the 2-year study.
 
Arm/Group Title PRN (Pro re Nata)
Hide Arm/Group Description

2 mg intravitreal aflibercept (Eylea) PRN, focal laser administered based on pre-specified criteria, 104 weeks

Aflibercept: pro re nata (PRN)

Focal Laser: Focal laser administered based on pre-specified criteria

All-Cause Mortality
PRN (Pro re Nata)
Affected / at Risk (%)
Total   1/60 (1.67%) 
Show Serious Adverse Events Hide Serious Adverse Events
PRN (Pro re Nata)
Affected / at Risk (%)
Total   19/60 (31.67%) 
Cardiac disorders   
Myocardial Infarction  [1]  2/60 (3.33%) 
Worsening congestive heart failure   1/60 (1.67%) 
Worsening arrhythmia   1/60 (1.67%) 
Worsening coronary artery disease   1/60 (1.67%) 
Eye disorders   
Acute vision loss secondary to vitreous hemorrhage   2/60 (3.33%) 
Acute vision loss due to worsening cataract   1/60 (1.67%) 
Gastrointestinal disorders   
Acute gastroenteritis   2/60 (3.33%) 
Hepatobiliary disorders   
Cholecystitis   1/60 (1.67%) 
Infections and infestations   
Worsening staph infection   1/60 (1.67%) 
Pneumonia  [2]  1/60 (1.67%) 
Flu   1/60 (1.67%) 
Osteomyelitis  [3]  1/60 (1.67%) 
Psychiatric disorders   
Depression   1/60 (1.67%) 
Renal and urinary disorders   
Chronic kidney disease   1/60 (1.67%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion   1/60 (1.67%) 
Skin and subcutaneous tissue disorders   
Cellulitis   1/60 (1.67%) 
Vascular disorders   
Deep vein thrombosis   1/60 (1.67%) 
Stroke   2/60 (3.33%) 
Hypotension   1/60 (1.67%) 
Blocked fistula   1/60 (1.67%) 
Blocked artery   1/60 (1.67%) 
Accelerated hypertension   1/60 (1.67%) 
Indicates events were collected by systematic assessment
[1]
Resulted in death of a subject.
[2]
Led to shortness of breath and altered mental status.
[3]
Caused by a MRSA infection.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PRN (Pro re Nata)
Affected / at Risk (%)
Total   26/60 (43.33%) 
Eye disorders   
Vitreous hemorrhage   9/60 (15.00%) 
Neovascularization elsewhere   2/60 (3.33%) 
Neovascularization of the disc   1/60 (1.67%) 
Worsening cataract   8/60 (13.33%) 
Corneal abrasion   1/60 (1.67%) 
Subconjunctival hemorrhage   1/60 (1.67%) 
Superficial punctate keratitis   1/60 (1.67%) 
Eye swelling post-cataract extraction   1/60 (1.67%) 
Posterior vitreous detachment   1/60 (1.67%) 
Floaters   5/60 (8.33%) 
Visual disturbance   1/60 (1.67%) 
Epiphora   1/60 (1.67%) 
Posterior capsule opafication   1/60 (1.67%) 
Iritis   1/60 (1.67%) 
Eye pain   1/60 (1.67%) 
Vitreous debris   1/60 (1.67%) 
Optic nerve pallor   1/60 (1.67%) 
Decreased vision   4/60 (6.67%) 
Ocular sensitivity   5/60 (8.33%) 
Indicates events were collected by systematic assessment
Limitations of the ENDURANCE study include the small population and employment of aflibercept re-treatment criteria that allowed physicians to use their varying clinical judgement in determining anti-VEGF re-treatment instead of a strict protocol.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Charles C. Wykoff
Organization: Retina Consultants of Houston
Phone: 7135243434
EMail: ccwmd@houstonretina.com
Publications:
Layout table for additonal information
Responsible Party: Charles C Wykoff, PhD, MD, Greater Houston Retina Research
ClinicalTrials.gov Identifier: NCT02299336     History of Changes
Other Study ID Numbers: The Endurance 1 Trial
First Submitted: October 15, 2014
First Posted: November 24, 2014
Results First Submitted: January 9, 2018
Results First Posted: June 7, 2018
Last Update Posted: June 4, 2019