Intravitreal Triamcinolone Acetonide Versus Laser for Diabetic Macular Edema (IVT)

This study has been completed.
Sponsor:
Collaborators:
Allergan
Information provided by:
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00367133
First received: August 3, 2006
Last updated: March 18, 2011
Last verified: March 2011
  Purpose

The study involves the enrollment of patients over 18 years of age with diabetic macular edema(DME). Patients with one study eye will be randomly assigned (stratified by visual acuity and prior laser) with equal probability to one of the three treatment groups:

  1. Laser photocoagulation
  2. 1mg intravitreal triamcinolone acetonide injection
  3. 4mg intravitreal triamcinolone acetonide injection

For patients with two study eyes (both eyes eligible at the time of randomization), the right eye (stratified by visual acuity and prior laser) will be randomly assigned with equal probabilities to one of the three treatment groups listed above. The left eye will be assigned to the alternative treatment (laser or triamcinolone). If the left eye is assigned to triamcinolone, then the dose (1mg or 4 mg) will be randomly assigned to the left eye with equal probability (stratified by visual acuity and prior laser).

The study drug, triamcinolone acetonide, has been manufactured as a sterile intravitreal injectable by Allergan. Study eyes assigned to an intravitreal triamcinolone injection will receive a dose of either 1mg or 4mg. There is no indication of which treatment regimen will be better.

Patients enrolled into the study will be followed for three years and will have study visits every 4 months after receiving their assigned study treatment. In addition, standard of care post-treatment visits will be performed at 4 weeks after each intravitreal injection.


Condition Intervention Phase
Diabetic Macular Edema
Procedure: Standard of Care Group
Drug: 1mg triamcinolone acetonide
Drug: 4mg triamcinolone acetonide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Trial Comparing Intravitreal Triamcinolone Acetonide and Laser Photocoagulation for Diabetic Macular Edema

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change In Visual Acuity [Measured With Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS)]Baseline to 2 Years. [ Time Frame: Baseline to 2 Years ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  • Median Change in Visual Acuity Baseline to 2 Years [ Time Frame: Baseline to 2 Years ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement.

  • Distribution of Change in Visual Acuity Baseline to 2 Years [ Time Frame: baseline to 2 years ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.


Secondary Outcome Measures:
  • Central Subfield Thickness at 2 Years [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Median central subfield thickness at two-years. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.

  • Mean Change in Central Subfield Thickness Baseline to 2 Years [ Time Frame: Baseline to 2 years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes and improvement.

  • Median Change in Central Subfield Thickness Baseline to 2 Years [ Time Frame: Baseline to 2 Years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.

  • Overall Central Subfield Thickening Decreased by >=50% Baseline to 2 Years [ Time Frame: Baseline to 2 Years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.

  • Central Subfield Thickness < 250 Microns at 2 Years [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.

  • Change in Visual Acuity From Baseline to 3 Years [ Time Frame: Baseline to 3 year ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement.

  • Change in Visual Acuity From Baseline to 3 Years [ Time Frame: Baseline to 3 year ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best Value on the scale=97, Worst Value=0

  • Distribution of Visual Acuity Change Baseline to 3 Years [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]
    Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale=97, worst=0

  • Central Subfield Thickness on Optical Coherence Tomography (OCT) at Three Years [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield.

  • Change in Central Subfield Thickness on OCT Baseline to 3 Years [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.

  • Change in Central Subfield Thickness on OCT Baseline to 3 Years [ Time Frame: baseline to 3 years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.

  • Percentage of Eyes With a Change in Central Subfield Thickness on OCT <250 Microns From Baseline to 3 Years [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]
    Overall central subfield change from baseline. Optical coherence Tomography (OCT) images were obtained by a certified operator using the Zeiss Stratus OCT machine. The average of 2 baseline central subfield thickness measurements was used for analysis.If the automated thickness measurements were judged by the reading center to be inaccurate, center point thickness was measured manually, and this value was used to impute a value for the central subfield. Negative change denotes an improvement.


Enrollment: 840
Study Start Date: July 2004
Study Completion Date: October 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Standard of care group: conventional treatment consisting of focal/grid photocoagulation.
Procedure: Standard of Care Group
Standard of care group: conventional treatment consisting of focal/grid photocoagulation.
Other Names:
  • soc with laser
  • modified ETDRS photocoagulation
Experimental: 2
Intravitreal injection of 1mg of triamcinolone acetonide
Drug: 1mg triamcinolone acetonide
Intravitreal injection of 1mg of triamcinolone acetonide at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.
Other Name: corticosteroid
Experimental: 3
Intravitreal injection of 4mg of triamcinolone acetonide
Drug: 4mg triamcinolone acetonide
4mg intravitreal triamcinolone acetonide injection at baseline. At each 4-month interval visit, the investigator will assess whether persistent or recurrent DME is present that warrants retreatment with the randomization assigned treatment. Retreatment, when indicated, will be performed within four weeks after the follow-up visit. Retreatment should not be performed sooner than 3.5 months from the time of the last treatment.
Other Name: corticosteroid

  Show Detailed Description

  Eligibility

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

To be eligible, the following inclusion criteria 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.
  4. Patient understands that (1) if both eyes are eligible at the time of randomization, one eye will receive intravitreal triamcinolone acetonide and one eye will receive laser, and (2) if only one eye is eligible at the time of randomization and the fellow eye develops DME later, then the fellow eye will not receive intravitreal triamcinolone acetonide if the study eye received intravitreal triamcinolone acetonide (however, if the study eye was assigned to the laser group, then the fellow eye may be treated with the 4mg dose of the study intravitreal triamcinolone acetonide formulation, provided the eye assigned to laser has not received an intravitreal injection; such an eye will not be a "study eye" but since it is receiving study drug, it will be followed for adverse effects).

Exclusion Criteria

A patient is not eligible if any of the following exclusion criteria are present:

7. History of chronic renal failure requiring dialysis or kidney transplant.

8. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure and glycemic control). Note: Patients in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.

9. Participation in an investigational trial within 30 days of study entry that involved treatment with any drug that has not received regulatory approval at the time of study entry.

10. Known allergy to any corticosteroid or any component of the delivery vehicle.

11. History of systemic (e.g., oral, IV, IM, epidural, bursal) corticosteroids within 4 months prior to randomization or topical, rectal, or inhaled corticosteroids in current use more than 2 times per week.

12. Patient is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 3 years of the study.

13. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). Note: If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.

Study Eye Eligibility

Inclusion

  1. Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (e-ETDRS) visual acuity score of ≥ 24 letters (i.e., 20/320 or better) and ≤73 letters (i.e., 20/40 or worse).
  2. Definite retinal thickening due to diabetic macular edema based on clinical exam involving the center of the macula.
  3. Mean retinal thickness on two Optical Coherence Tomography (OCT) measurements ≥250 microns in the central subfield.
  4. Media clarity, pupillary dilation, and patient cooperation sufficient for adequate fundus photographs.

    Exclusion

  5. Macular edema is considered to be due to a cause other than diabetic macular edema.
  6. 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).
  7. 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.)
  8. 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).
  9. History of prior treatment with intravitreal corticosteroids.
  10. History of peribulbar steroid injection within 6 months prior to randomization.
  11. History of focal/grid macular photocoagulation within 15 weeks (3.5 months) prior to randomization.Note: Patients are not required to have had prior macular photocoagulation to be enrolled. If prior macular photocoagulation has been performed, the investigator should believe that the patient may possibly benefit from additional photocoagulation.
  12. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.
  13. Anticipated need for PRP in the 4 months following randomization.
  14. History of prior pars plana vitrectomy.
  15. 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.
  16. History of YAG capsulotomy performed within 2 months prior to randomization.
  17. Intraocular pressure ≥25 mmHg.
  18. History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.) Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure (IOP) is <25 mm Hg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mm Hg, then the above criteria for ocular hypertension eligibility must be met.
  19. History of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.
  20. History of prior herpetic ocular infection.
  21. Exam evidence of ocular toxoplasmosis.
  22. Aphakia.
  23. Exam evidence of pseudoexfoliation.
  24. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

In patients with only one eye meeting criteria to be a study eye at the time of randomization, the fellow eye must meet the following criteria:

  1. Best corrected e-ETDRS visual acuity score ≥19 letters (i.e., 20/400 or better).
  2. No prior treatment with intravitreal corticosteroids.
  3. Intraocular pressure < 25 mmHg.
  4. No history of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma.)Note: Angle-closure glaucoma is not an exclusion. A history of ocular hypertension is not an exclusion as long as (1) intraocular pressure is <25 mmHg, (2) the patient is using no more than one topical glaucoma medication, (3) the most recent visual field, performed within the last 12 months, is normal (if abnormalities are present on the visual field they must be attributable to the patient's diabetic retinopathy), and (4) the optic disc does not appear glaucomatous. If the intraocular pressure is 22 to <25 mmHg, then the above criteria for ocular hypertension eligibility must be met.
  5. No history of steroid-induced intraocular pressure elevation that required IOP-lowering treatment.
  6. No exam evidence of pseudoexfoliation.
  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: NCT00367133

  Show 84 Study Locations
Sponsors and Collaborators
Diabetic Retinopathy Clinical Research Network
Allergan
Investigators
Study Chair: Michael Ip, M.D. University of Wisconsin Medical School
  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: NCT00367133     History of Changes
Other Study ID Numbers: NEI-105, U10EY018817-03, U10EY014229-07, U10EY014231-09
Study First Received: August 3, 2006
Results First Received: July 14, 2009
Last Updated: March 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Diabetic Retinopathy Clinical Research Network:
diabetic
macular
edema
intravitreal
triamcinolone
laser
photocoagulation
DME

Additional relevant MeSH terms:
Edema
Macular Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Triamcinolone hexacetonide
Triamcinolone
Triamcinolone Acetonide
Triamcinolone diacetate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014