Safety and Efficacy of Triamcinolone Acetonide Combined With Laser, Bevacizumab Combined With Laser Versus Laser Alone for the Treatment of Diffuse Non-tractional Diabetic Macular Edema (ALBA)

Randomized Multicenter Clinical Trial of Three Parallel Groups to Estimate the Safety and Efficacy of Triamcinolone Acetonide Combined With Laser, Bevacizumab Combined With Laser Versus Laser Alone for the Treatment of Diffuse Non-tractional Diabetic Macular Edema.

This clinical trial is designed to investigate differences in terms of efficacy (mean change in best corrected visual acuity obtained after 12 months of treatment) and safety, of 3 therapeutic estrategies for non-tractional macular edema in diabetic patients: a) laser alone; b) laser plus tiramcinolon; and c) laser plus bevacizumab.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Other: Grid laser; Drug: Triamcinolone Acetonide; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Las Palmas de Gran Canaria, Spain
    • Hospital Universitario Dr Negrin

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

To be eligible, the following inclusion criteria must be met:

1. Age ≥18 years from both sexes. Women of childbearing age should use adequate contraception methods and submit a negative pregnancy test.
2. Diagnosis of diabetes mellitus type 1 or type 2 (documented by ADA or WHO guidelines) and serum HbA1c <11% at the time of randomization (determinations done in the last two months).
3. Patient able to give informed consent.
4. Eye with clear media, pupil dilation and patient able to cooperate to perform retinography, OCT and fluorescein angiography.

5. Patients with clinically significant diabetic macular edema; the patient must have at least one:

   5.1) retinal thickening within 500 μ from the center or 5.2) hard exudates within 500 μ from the center if associated with adjacent retinal thickening or 5.3) the size of retinal thickening at least 1 area disc, part of which is less than 1 DD of the center.

6. Patients with diffuse diabetic macular edema.
7. Patients with not tractional diabetic macular edema.

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

1. Women of childbearing age not using adequate contraceptive methods.
2. Pregnancy and lactation. Pregnancy test was performed before starting treatment.
3. Chronic renal failure requiring dialysis or kidney transplantation.
4. Allergy to any of the drugs included in the study.
5. Systemic use of steroids in the last 4 months.
6. Patient intends to change his place of residence within 3 years after recruitment, whenever you go to an area not covered by the study.
7. Blood pressure>180/110. If blood pressure is brought below 180/110 by anti-hypertensive treatment, patient can become eligible.
8. HbA1c> 11% in the current analysis or done in the last 2 months.
9. 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 hare exudates, nonretinal condition).
10. 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.)
11. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more
12. History of prior treatment with intravitreal corticosteroids or intravitreal antiangiogenic.
13. History of peribulbar steroid injection within 6 months prior to randomization.
14. History of focal, grid or panretinal photocoagulation within 4 months prior to randomization.
15. Need of panretinal photocoagulation in the first 4 months of treatment.
16. History of prior pars plana vitrectomy.
17. Major ocular surgery (including cataract extraction, scleral buckle, vitrectomy, etc.) within prior 6 months or anticipated within the next 6 months following randomization.
18. History of YAG capsulotomy performed within 2 months prior to randomization.
19. Intraocular pressure >25mmHg.
20. 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.
21. History of cortisone-induced glaucoma that required IOP-lowering treatment.
22. History of prior herpetic ocular infection.
23. Exam evidence of ocular toxoplasmosis.
24. Aphakia.
25. Presence of pseudoexfoliation.
26. Evidence of external ocular infection, including: conjunctivitis, chalazion and blepharitis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab	Drug: Bevacizumab; Bevacizumab (1.25 mg initially, weeks 6 and 12) followed by modified grid laser therapy after3-4 weeks; Other Names: Avastin
Active Comparator: Grid laser; It's a reference standard as the treatment which is currently accepted for NTDDME	Other: Grid laser; Grid laser therapy acts as the standard to refer to as it is the treatment which is currently accepted by EMDDNT.
Experimental: Triamcinolone 4 mg	Drug: Triamcinolone Acetonide; Triamcinolone 4 mg followed by modified grid laser therapy after 3-4 weeks; Other Names: Triesence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best-Corrected Visual Acuity (BCVA)	To evaluate the effect on best-corrected visual acuity (BCVA) of intravitreal triamcinolone (Triesence ®) or bevacizumab (Avastin ®) in combination with grid laser therapy compared to grid laser therapy alone after 12 months of treatment, in diabetic patients with not tractional diffuse macular edema (NTDDEM)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety of intravitreal Triesence (r)	Type of adverse events, severity and number of Participants with Adverse Events as a Measure of Safety and Tolerability.	Baseline, 3m, 6m and 12 months
To measure average change in mean central macular thickness in each group.	To measure average change in mean central macular thickness (in microns) obtained by Optical Coherence Tomography (OCT) at each follow-up visits compared to the baseline visit in each of the three groups.	Baseline and 3, 6 and 12 months after the treatment was initiated.
To assess the safety of intravitreal Avastin (r)	Type of adverse events, severity and number of Participants with Adverse Events as a Measure of Safety and Tolerability	Baseline, 3m, 6m and 12 months
To assess the safety of intravitreal grid photocoagulation	Type of adverse events, severity and number of Participants with Adverse Events as a Measure of Safety and Tolerability	Baseline, 3m, 6m and 12 months

Collaborators and Investigators

• Sponsor: Hospital Universitario de Canarias
• Investigators: Principal Investigator: Alicia Pareja, MD, Hospital Universitario de Canarias

Publications and helpful links

General Publications

• Pareja-Rios A, de Armas-Ramos E, Aldea-Perona A, Bonaque-Gonzalez S. Alone laser versus bevacizumab plus laser for diffuse diabetic macular edema (ALBA randomized trial). Ther Adv Ophthalmol. 2021 Jan 15;13:2515841420988210. doi: 10.1177/2515841420988210. eCollection 2021 Jan-Dec.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 7, 2011
• First Submitted That Met QC Criteria: April 4, 2012
• First Posted (Estimate): April 6, 2012

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: ALBA09