Prevention of Macular Edema In Patients With Diabetic Retinopathy Undergoing Cataract Surgery (PROMISE)

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Retinopathy
• Intervention / Treatment: Drug: Sham; Drug: Aflibercept

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cole Eye Institute, Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: 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.	Drug: Sham; Sham injection. No actual injection. No medication is used.
Active Comparator: 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.	Drug: 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.; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Retinal Thickness	The change in macular edema as measured by SD-OCT (spectral domain ocular coherence tomography)at 90 days	Day 90

Collaborators and Investigators

• Sponsor: Rishi Singh
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Rishi Singh, M.D., Cole Eye Institute, Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): April 25, 2018
• Study Completion (Actual): January 14, 2020

Study Registration Dates

• First Submitted: October 30, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (Estimate): November 20, 2013

Study Record Updates

• Last Update Posted (Actual): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 12, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Diabetic Retinopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Endocrine System Diseases; Diabetic Angiopathies; Diabetes Complications; Diabetes Mellitus; Retinal Degeneration; Macular Degeneration; Lens Diseases; Retinal Diseases; Diabetic Retinopathy; Macular Edema; Cataract; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: PROMISE Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED