Intravitreal Bevacizumab and Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA) - Full Text View

Purpose

Intravitreal triamcinolone has been effective for central macular thickness reduction and concomitant visual acuity improvement in patients with diabetic macular edema (DME). VEGF is a very effective inducer of permeability, being 50.000 times more potent than histamine, and may exert its effect on retinal vascular permeability by altering tight-junctions proteins, such as occluding and VE-cadherin. Based on these principles, there is a rationale for anti-VEGF agents treatment of increased retinal capillary permeability conditions, such as diabetic macular edema. Therefore, the purpose of this study is to evaluate the effects of intravitreal bevacizumab and intravitreal triamcinolone associated to laser photocoagulation for diabetic macular edema.

Condition	Intervention	Phase
Diabetic Macular Edema	Procedure: Laser photocoagulation Drug: Intravitreal triamcinolone Drug: Intravitreal bevacizumab	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Intravitreal Bevacizumab and Intravitreal Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA)

Resource links provided by NLM:

MedlinePlus related topics: Edema

Drug Information available for: Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Triamcinolone hexacetonide Bevacizumab

U.S. FDA Resources

Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:

Best Corrected Visual acuity [ Time Frame: One Year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Macular Mapping Test [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
Multifocal Electroretinogram [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
Central Macular Thickness [ Time Frame: One Year ] [ Designated as safety issue: Yes ]


Enrollment:	12
Study Start Date:	October 2009
Study Completion Date:	November 2011
Primary Completion Date:	November 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Laser Group Focal / grid Laser photocoagulation in diabetic macular edema	Procedure: Laser photocoagulation Focal / grid photocoagulation for diabetic macular edema according to ETDRS guidelines
Experimental: Triamcinolone group Intravitreal triamcinolone associated to laser photocoagulation for diabetic macular edema	Drug: Intravitreal triamcinolone Intravitreal preservative-free triamcinolone (4mg) associated to focal photocoagulation for diabetic macular edema on baseline; Re-treatment at weeks 20 and 40 if CMT>275um Other Name: Triancinolona (Ophthalmos)
Experimental: Bevacizumab group Intravitreal Bevacizumab associated to laser photocoagulation for diabetic macular edema	Drug: Intravitreal bevacizumab Intravitreal bevacizumab (1.5mg) associated to focal photocoagulation for diabetic macular edema at baseline; Re-treatment at weeks 20 and 40 if CMT>275um Other Name: Avastin

Detailed Description:

Macular edema is a leading cause of decreased visual acuity in patients with diabetic retinopathy1,2.

Laser photocoagulation is the standard of care treatment for diabetic macular edema, based on ETDRS and recent clinical trials findings3,4. However, because visual acuity improvement post-laser is observed infrequently, and because of the frequent recurrence or persistence of DME (refractory DME) after appropriate laser treatment, particularly in eyes presenting with angiographically diffuse macular edema5-9, there is a need for alternative treatments for the management of DME. In addition, for some patients with significant cataract, precise visualization of posterior pole structures may not be possible, so that pharmacological therapy with intravitreal agents may be preferable over laser treatment.

Recent studies have shown promising results of pharmacological therapies for Diabetic macular edema. Triamcinolone has shown similar results when compared to ranibizumab and deferred focal/grid LASER in pseudophakic eyes (DRCRnet, prompt versus deferred). Ranibizumab associated with deferred LASER or as monotherapy has also shown promising results (RISE and RIDE). However, there are several concerns regarding long-term intravitreal injections therapies that include economic feasibility for the public health system, risk of endophthalmitis and patient acceptability. For these reasons, the present study decided to check associations between LASER and drug therapy, in an attempt to improve focal/grid laser outcomes with reduced number of intravitreal injections.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinically significant DME - by biomicroscopic evaluation with generalized breakdown of the inner blood-retina barrier with diffuse fluorescein leakage involving the foveal center and most of the macular area on fluorescein angiography
Snellen logarithm of minimum angle of 20/40 or worse
Central macular thickness greater than 275 µm on optical coherence tomography (OCT)

Exclusion Criteria:

Glycosylated hemoglobin rate above 10%
History of glaucoma or ocular hypertension
Systemic corticoid therapy
History of thromboembolic event (including myocardial infarction or cerebral vascular accident)
Major surgery within the prior 6 months or planned within the next 28 days
Uncontrolled hypertension
Severe systemic disease
Any condition affecting documentation or follow-up

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: NCT00997191

Locations


Brazil
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
Ribeirão Preto, São Paulo, Brazil

Sponsors and Collaborators

University of Sao Paulo

Fundação de Amparo à Pesquisa do Estado de São Paulo

Investigators


Study Chair:	Maria L Paccola, MD	HC FMRP - USP
Study Chair:	André M V Messias, PhD	HCFMRP - USP
Study Director:	Bianka Y N Y Katayama, MD	HC FMRP - USP
Principal Investigator:	Rodrigo Jorge, PhD	HC FMRP - USP
Study Chair:	Rogério A Costa, PhD	HC FMRP - USP

More Information

Publications:

Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol. 2008 Jan;92(1):76-80. Epub 2007 Oct 26.

Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon's infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial. Invest Ophthalmol Vis Sci. 2005 Oct;46(10):3845-9.

Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec;103(12):1796-806.

Garner A. Pathology of diabetic retinopathy. Br Med Bull. 1970 May;26(2):137-42. Review.

Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

Jorge R, Costa RA, Calucci D, Cintra LP, Scott IU. Intravitreal bevacizumab (Avastin) for persistent new vessels in diabetic retinopathy (IBEPE study). Retina. 2006 Nov-Dec;26(9):1006-13.

Jonas JB, Kreissig I, Söfker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol. 2003 Jan;121(1):57-61.

Lee CM, Olk RJ. Modified grid laser photocoagulation for diffuse diabetic macular edema. Long-term visual results. Ophthalmology. 1991 Oct;98(10):1594-602.

Kang SW, Sa HS, Cho HY, Kim JI. Macular grid photocoagulation after intravitreal triamcinolone acetonide for diffuse diabetic macular edema. Arch Ophthalmol. 2006 May;124(5):653-8.

Karacorlu M, Ozdemir H, Senturk F, Arf Karacorlu S, Uysal O. Macular function by multifocal electroretinogram in diabetic macular edema after intravitreal triamcinolone acetonide injection. Eur J Ophthalmol. 2008 Jul-Aug;18(4):601-8.

Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, Baumal C. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002 May;109(5):920-7.

Kook D, Wolf A, Kreutzer T, Neubauer A, Strauss R, Ulbig M, Kampik A, Haritoglou C. Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina. 2008 Oct;28(8):1053-60. doi: 10.1097/IAE.0b013e318176de48.

Larsson J, Zhu M, Sutter F, Gillies MC. Relation between reduction of foveal thickness and visual acuity in diabetic macular edema treated with intravitreal triamcinolone. Am J Ophthalmol. 2005 May;139(5):802-6.

Soheilian M, Ramezani A, Bijanzadeh B, Yaseri M, Ahmadieh H, Dehghan MH, Azarmina M, Moradian S, Tabatabaei H, Peyman GA. Intravitreal bevacizumab (avastin) injection alone or combined with triamcinolone versus macular photocoagulation as primary treatment of diabetic macular edema. Retina. 2007 Nov-Dec;27(9):1187-95.

Vujosevic S, Pilotto E, Bottega E, Benetti E, Cavarzeran F, Midena E. Retinal fixation impairment in diabetic macular edema. Retina. 2008 Nov-Dec;28(10):1443-50. doi: 10.1097/IAE.0b013e318183571e.


Responsible Party:	Rodrigo Jorge, Professor, University of Sao Paulo
ClinicalTrials.gov Identifier:	NCT00997191 History of Changes
Other Study ID Numbers:	6826/2009
Study First Received:	October 15, 2009
Last Updated:	February 28, 2013
Health Authority:	Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo:


Bevacizumab Diabetes Intravitreal	Macular edema triamcinolone VEGF

Additional relevant MeSH terms:


Edema Macular Edema Signs and Symptoms Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Bevacizumab Triamcinolone hexacetonide Triamcinolone Triamcinolone Acetonide Triamcinolone diacetate Angiogenesis Inhibitors	Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents Anti-Inflammatory Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Immunosuppressive Agents Immunologic Factors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016

Intravitreal Bevacizumab and Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA) (IBeTA)