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A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00336323
First received: June 9, 2006
Last updated: July 28, 2011
Last verified: July 2011
  Purpose

This study will provide preliminary data on the dose and dose interval related effects of intravitreally administered Avastin on retinal thickness and visual acuity in subjects with Diabetic Macular Edema (DME) to aid in planning a phase 3 trial.

In addition, this study will provide preliminary data on the safety of intravitreally administered Avastin in subjects with DME.


Condition Intervention Phase
Diabetic Retinopathy
Procedure: Laser Photocoagulation
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)

Resource links provided by NLM:


Further study details as provided by Diabetic Retinopathy Clinical Research Network:

Primary Outcome Measures:
  • Change in Central Subfield Retinal Thickness From Baseline Over All Study Visits [ Time Frame: Baseline to 3,6,9, and 12 weeks ] [ Designated as safety issue: No ]
    Change in central subfield retinal thickness from baseline measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading. Negative changes represent a decrease in retinal thickening.

  • Percentage of Participants With <250 Microns or ≥ 50% Reduction in Retinal Thickening From Baseline Over All Study Visits [ Time Frame: Baseline to 3,6,9, and 12 Weeks ] [ Designated as safety issue: No ]
    Central subfield retinal thickness measured on Optical Coherence Tomography (OCT). OCT images were obtained at each visit following pupil dilation by a certified operator using the OCT3 machine (Carl Zeiss Meditec Inc., Dublin, CA). Scans were 6 mm length and included the 6 radial line pattern for quantitative measures and the cross hair pattern (6-12 to 9-3 o'clock) for qualitative assessment of retinal morphology. The OCT scans were sent to the DRCR.net Reading Center for grading.


Secondary Outcome Measures:
  • Change in Visual Acuity Letter Score From Baseline Over All All Study Visits [ Time Frame: Baseline to 3,6,9, and 12 weeks ] [ Designated as safety issue: No ]
    Change in visual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; positive change represents an improvement in letter score.

  • Distribution of Change in Visual Acuity Over All Study Visits [ Time Frame: Baseline to 3,6,9, and 12 weeks ] [ Designated as safety issue: No ]
    Visual acuity letter score as measured using an electronic visual acuity testing machine based on the electronic Early Treatment for Diabetic Retinopathy Study(E-ETDRS) technique. At baseline and at each follow up visit, best corrected visual acuity was measured at 3 meters by a certified tester using an electronic procedure based on the E-ETDRS method. Letter score best value = 97 and worst value = 0; an increase in a letter score by 10 is considered clinically significant.


Enrollment: 121
Study Start Date: June 2006
Study Completion Date: February 2008
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Laser photocoagulation at baseline
Procedure: Laser Photocoagulation
Laser photocoagulation at baseline; If edema present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart
Experimental: 2
1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Drug: Bevacizumab
1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Other Names:
  • Avastin
  • anti-VEGF drug
Experimental: 3
2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Drug: Bevacizumab
2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks
Other Names:
  • Avastin
  • anti-VEGF drug
Experimental: 4
1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)
Drug: Bevacizumab
1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks)
Other Names:
  • Avastin
  • anti-VEGF drug
Experimental: 5
1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
Drug: Bevacizumab
1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
Other Names:
  • Avastin
  • anti-VEGF drug

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

SUBJECT-LEVEL INCLUSION CRITERIA

To be eligible, the following inclusion criteria (1-3) must be met:

  1. Age >= 18 years
  2. Diagnosis of diabetes mellitus (type 1 or type 2)
  3. Able and willing to provide informed consent.

    EXCLUSION

    A subject is not eligible if any of the following exclusion criteria (4-13) are present:

  4. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
  5. 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).
  6. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
  7. Known allergy to any component of the study drug.
  8. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110).
  9. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
  10. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization.
  11. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization.
  12. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 6 months.
  13. Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 6 months of the study.

STUDY EYE CRITERIA

The subject must have one eye meeting all of the inclusion criteria (a-e) and none of the exclusion criteria (f-r) listed below.

Subjects can have only one study eye. If both eyes are eligible, the study eye will be selected by the investigator and subject.

The eligibility criteria for a study eye are as follows:

INCLUSION

  1. Best corrected E-ETDRS visual acuity letter score of >= 24 (i.e., 20/320 or better) and <= 78 (i.e., 20/32 or worse) within 8 days of randomization.
  2. On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
  3. OCT central subfield >=275 microns within 8 days of randomization.
  4. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
  5. If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

    EXCLUSION

    The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

  6. Macular edema is considered to be due to a cause other than diabetic macular edema.
  7. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition).
  8. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
  9. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  10. History of treatment for DME at any time in the past 3 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).
  11. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.
  12. Anticipated need for PRP in the 6 months following randomization.
  13. History of prior pars plana vitrectomy.
  14. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization.
  15. History of YAG capsulotomy performed within 2 months prior to randomization.
  16. Aphakia.
  17. Uncontrolled glaucoma (in investigator's judgment).
  18. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

FELLOW EYE CRITERIA

The fellow eye must meet the following criteria:

  1. Best corrected E-ETDRS visual acuity letter score >= 19 (i.e., 20/400 or better).
  2. No anti-VEGF treatment within the past 3 months and no expectation of such treatment in next 3 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336323

  Show 34 Study Locations
Sponsors and Collaborators
Diabetic Retinopathy Clinical Research Network
Investigators
Study Chair: Ingrid U. Scott, M.D., M.P.H. Penn State College of Medicine
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Roy W. Beck, M.D., Ph.D., Director, Jaeb Center for Health Research (DRCR.net)
ClinicalTrials.gov Identifier: NCT00336323     History of Changes
Other Study ID Numbers: NEI-129, U10EY018817-03, U10EY014229-07, U10EY014231-09, EY14231, EY14269, EY14229
Study First Received: June 9, 2006
Results First Received: March 16, 2011
Last Updated: July 28, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Diabetic Retinopathy Clinical Research Network:
diabetic
macular
edema
avastin
bevacizumab
anti-VEGF
retinal thickness
visual acuity
DME

Additional relevant MeSH terms:
Diabetic Retinopathy
Macular Edema
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endocrine System Diseases
Eye Diseases
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Vascular Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014