A Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and Ranibizumab for Diabetic Macular Edema
Overview
- Phase
- Phase 3
- Intervention
- 0.3 mg intravitreal ranibizumab
- Conditions
- Diabetic Macular Edema
- Sponsor
- Jaeb Center for Health Research
- Enrollment
- 660
- Locations
- 90
- Primary Endpoint
- Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Although multiple studies have suggested that treatment with ranibizumab is safe and efficacious and superior to focal/grid laser alone for patients with center-involved diabetic macular edema (DME), there may be barriers in place to widespread adoption of ranibizumab use given its high cost per dose and the need for multiple treatments over time. Prioritizing resources from a public health policy perspective could be easier if more precise estimates regarding the risks and benefits of other anti-vascular endothelial growth factor (anti-VEGF) therapies were available, especially when the difference in costs could be billions of dollars over just a few years. Thus, there is a clear rationale at this time to explore potential anti-VEGF alternatives to ranibizumab that might prove to be as or more efficacious, might deliver equally lasting or longer-lasting treatment effects, and cost substantially less. Of the potentially available alternative anti-VEGF agents for this trial, bevacizumab and aflibercept are the best candidates for a direct comparison study. Bevacizumab shares the most similar molecular structure, costs far less, and is widely available. Furthermore, there is already preliminary evidence to suggest that it may be efficacious in the treatment of DME and it is already being widely used for this indication. Although aflibercept has a similar cost per unit dose to ranibizumab, it has the potential to decrease treatment burden and associated cost. If results from a comparative trial demonstrate improved efficacy or suggest similar efficacy of bevacizumab or aflibercept over ranibizumab, this information might give clinicians scientific rationale to substitute either one of these drugs for ranibizumab in the treatment of DME, and might thereby have substantial implications for public policy in terms of future estimates of health care dollars and possibly number of treatments necessary for anti-VEGF treatment of diabetic macular disease.
Because of its availability and lower cost, bevacizumab is already currently in widespread clinical use for treatment of DME despite the lack of FDA approval for this indication. Thus, a clinical trial that suggested whether bevacizumab could be used as a safe and efficacious alternative to ranibizumab could substantially impact nationwide practice patterns for treatment of DME by either validating the current use of bevacizumab or by demonstrating improved outcomes with ranibizumab or aflibercept treatment for DME.
Study Objective The primary objective of the proposed research is to compare the efficacy and safety of (1) intravitreal aflibercept, (2) intravitreal bevacizumab, and (3) intravitreal ranibizumab when given to treat central-involved DME in eyes with visual acuity of 20/32 to 20/320.
Detailed Description
A five year follow-up visit is being conducted to gather information on long term outcomes
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years
- •Individuals \<18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.
- •Diagnosis of diabetes mellitus (type 1 or type 2)
- •Any one of the following will be considered to be sufficient evidence that diabetes is present:
- •Current regular use of insulin for the treatment of diabetes
- •Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
- •Documented diabetes by American Diabetes Association and/or World Health Organization criteria (see Procedures Manual for definitions)
- •At least one eye meets the following study eye criteria:
- •Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score ≤ 78 (i.e., 20/32 or worse) and ≥ 24 (i.e., 20/320 or better) within eight days of randomization.
- •On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
Exclusion Criteria
- •Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
- •A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
- •Individuals in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.
- •Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied at the time of study entry.
- •Note: study participants cannot receive another investigational drug while participating in the study.
- •Known allergy to any component of the study drug.
- •Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110).
- •If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
- •Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
- •Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.
Arms & Interventions
Ranibizumab
Intervention: 0.3 mg intravitreal ranibizumab
Aflibercept
Intervention: 2.0 mg intravitreal aflibercept
Bevacizumab
Intervention: 1.25 mg intravitreal bevacizumab
Outcomes
Primary Outcomes
Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score 78-69
Time Frame: Baseline to 1-year
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.
Overall Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year
Time Frame: Baseline to 1-year
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.
Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 1-year: Baseline Visual Acuity Letter Score <69
Time Frame: Baseline to 1-year
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.
Secondary Outcomes
- Overall Change in Optical Coherence Tomography Central Subfield Thickness(baseline to 1-year)
- Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score 78-69(baseline to 1-year)
- Total Number of Laser Treatments(between 24 weeks and 1 year)
- Change in Optical Coherence Tomography Central Subfield Thickness: Baseline Visual Acuity Letter Score <69(baseline to 1-year)
- Overall Change in Retinal Volume(Baseline to 1-year)
- Total Number of Injections Prior to 1 Year(Baseline to 1-year)
- Eyes Receiving 1 or More Alternative Treatments for DME Other Than Laser(Baseline to 1-year)