Diabetic Retinopathy
Conditions
Keywords
Diabetes, Diabetic Retinopathy
Brief summary
To determine the safety and efficacy of intravitreal Aflibercept (Eylea) injection in patients with diabetic retinopathy in the prevention of macular edema following cataract surgery.
Detailed description
Diabetic retinopathy patients who are at risk of developing macular edema (defined as ≥ 30 % increase from pre-operative baseline in central subfield macular thickness) within 90 days following cataract surgery. Diabetic patients are defined as those who have either Type 1 or Type 2 diabetes. The patients must have either mild, moderate, or severe non proliferative retinopathy or treated proliferative retinopathy. Patients must be 18 years of age and older, of any race and either sex, requiring cataract extraction with planned implantation of a posterior chamber intraocular lens into the lens capsule.
Interventions
DRUGAflibercept
Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection.
DRUGSham
Sham injection. No actual injection. No medication is used.
Sponsors
Regeneron Pharmaceuticals
Rishi Singh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A patient must meet the following criteria to be eligible for inclusion in the study: 1. Must be 18 years of age and older, of any race and either sex, who have a cataract, and are planning to undergo cataract extraction by phacoemulsification with the implantation of a posterior chamber intraocular lens into the lens capsule 2. History of Type I or Type II diabetes 3. NPDR: non-proliferative diabetic retinopathy (mild, moderate, or severe) or inactive proliferative disease in the study eye as defined by the International Clinical Diabetic Retinopathy Disease Severity Scale 4. Willing and able to comply with clinic visits and study-related procedures 5. Patients must be able to understand and sign an informed consent that has been approved by an Institutional Review Board (IRB) 6. Central subfield macular thickness ≤ 320 μm in the study eye prior to cataract surgery as determined by SD-OCT and confirmed by the reading center 7. Absence of clinically significant macular edema (CSME) in the study eye as detected by clinical exam 8. Patients must have visual acuity of 20/20-20/200
Exclusion criteria
A patient who meets any of the following criteria will be excluded from the study: 1. Signs of vitreomacular traction or epiretinal membrane in the study eye as detected by reading center or investigator 2. Current or previous ocular disease in the study eye that in the opinion of the investigator may confound assessment of the macula, the retina, or central vision other that diabetic retinopathy 3. Active proliferative diabetic retinopathy in the study eye 4. Planned multiple procedures for study eye during the cataract/IOL implantation surgery (e.g., trabeculectomy, corneal transplant) 5. Patients who have received corneal transplants in the study eye 6. Patients with current or history of chronic or recurrent ocular infections or inflammation in the study eye 7. Patients with a visually nonfunctional fellow eye based upon the assessment by the investigator 8. Patients who are immunocompromised (e.g., patients receiving chemotherapy irradiation therapy, patients with AIDS, leukemia, or cachexia) or patients receiving dialysis 9. Use of medications known to affect the macula, including hydroxychloroquinine (Plaquenil) and phenothiozines (e.g., thioridazine \[Mellaril\], chloropromazine \[Thorazine\]) or supplemental niacin ≥3 grams/day 10. Use of systemic steroids, NSAIDS (non-steroidal anti-inflammatory drugs), anti-VEGF agents within 7 days prior to surgery (through study exit). Daily doses of aspirin, up to 325 mg, will be permitted. 11. Use of topical ocular NSAIDS and steroids, in the study eye, within 7 days prior to surgery 12. Treatment with intraocular or periocular steroids in the study eye within 3 months prior to surgery 13. Focal photocoagulation for the treatment of diabetic macular edema in the study eye within 6 months of the pre-operative baseline visit (Note: peripheral retina treatment for retinal tear or lattice degeneration is permitted) 14. Intravitreal anti-VEGF (vascular endothelial growth factor) treatment in the study eye within 6 months of the pre-operative baseline visit 15. Patients with a known hypersensitivity to NSAIDs or steroids or any component of the study medication. 16. Use of a topical ophthalmic prostaglandin (e.g., TRAVATAN, XALATAN) within 4 days of surgery through study exit 17. Any concurrent intraocular condition in the study eye that, in the opinion of the investigator, could require either medical or surgical intervention during the 90 day study period. 18. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety. 19. Pregnant or breast-feeding women -
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Ocular and Non-Ocular Adverse Events | Day 90 | Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score | Day 90 | Change from baseline in best-corrected visual acuity (BCVA) score and BCVA score at Day 90 as measured by ETDRS (early treatment diabetic retinopathy study) There were no sub scales used. These are common methods for ophthalmology studies to report their findings. The scale provided is the Electronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) best corrected visual acuity scale. Values that are higher are considered better and values that are lower are considered worse. Minimum E-ETDRS was 24 E-ETDRS letters and maximum E-ETDRS was 80 E-ETDRS letters. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Retinal Thickness | Day 90 | The change in macular edema as measured by SD-OCT (spectral domain ocular coherence tomography)at 90 days |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Injection Patients will be sequentially randomized to treatment with a sham injection at the time of surgery. The sham injection is accomplished by pressing an empty syringe against the eye wall without penetration. This will be administered post cataract excision by the Prinicipal Investigator. The patient will be masked as to which Arm they are assigned.
Sham: Sham injection. No actual injection. No medication is used. | 15 |
| Intravitreal Aflibercept Injection Patients will be sequentially randomized to treatment with Aflibercept 2 mg via intravitreal injection (0.05 mL or 50 microliters) at the time of surgery. This will be administered post cataract excision by the Principal Investigator. The patient will be masked as to which Arm they are assigned.
Aflibercept: Patients will be assigned to treatment with 2 mg intravitreal Aflibercept injection (0.05 mL or 50 microliters) administered at the time of surgery (post cataract excision) or sham injection. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Sham Injection | Total | Intravitreal Aflibercept Injection |
|---|---|---|---|
| Age, Customized | 66 years | 66 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 25 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 16 Participants | 10 Participants |
| Region of Enrollment United States | 15 participants | 30 participants | 15 participants |
| Sex: Female, Male Female | 10 Participants | 16 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 14 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 14 / 15 | 10 / 15 |
| serious Total, serious adverse events | 2 / 15 | 3 / 15 |
Outcome results
Primary
Number of Participants With Ocular and Non-Ocular Adverse Events
Number of participants with ocular and non-ocular adverse events (AEs) in both treatment arms.
Time frame: Day 90
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sham Injection | Number of Participants With Ocular and Non-Ocular Adverse Events | At least 1 Ocular Adverse Event | 11 Participants |
| Sham Injection | Number of Participants With Ocular and Non-Ocular Adverse Events | At least 1 Non-Ocular Adverse Event | 5 Participants |
| Intravitreal Aflibercept Injection | Number of Participants With Ocular and Non-Ocular Adverse Events | At least 1 Ocular Adverse Event | 10 Participants |
| Intravitreal Aflibercept Injection | Number of Participants With Ocular and Non-Ocular Adverse Events | At least 1 Non-Ocular Adverse Event | 3 Participants |
Secondary
Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score
Change from baseline in best-corrected visual acuity (BCVA) score and BCVA score at Day 90 as measured by ETDRS (early treatment diabetic retinopathy study) There were no sub scales used. These are common methods for ophthalmology studies to report their findings. The scale provided is the Electronic-Early Treatment in Diabetic Retinopathy Scale (E-ETDRS) best corrected visual acuity scale. Values that are higher are considered better and values that are lower are considered worse. Minimum E-ETDRS was 24 E-ETDRS letters and maximum E-ETDRS was 80 E-ETDRS letters.
Time frame: Day 90
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sham Injection | Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score | 8.52 Number of Letters Read Correctly |
| Intravitreal Aflibercept Injection | Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score | 9.88 Number of Letters Read Correctly |
Other Pre-specified
Change From Baseline in Retinal Thickness
The change in macular edema as measured by SD-OCT (spectral domain ocular coherence tomography)at 90 days
Time frame: Day 90
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sham Injection | Change From Baseline in Retinal Thickness | 50.32 Microns |
| Intravitreal Aflibercept Injection | Change From Baseline in Retinal Thickness | 18.48 Microns |