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

Tracking Information
First Submitted Date ICMJE	October 15, 2009
First Posted Date ICMJE	October 19, 2009
Last Update Posted Date	March 4, 2013
Study Start Date ICMJE	October 2009
Actual Primary Completion Date	November 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 16, 2009)	Best Corrected Visual acuity [ Time Frame: One Year ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00997191 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 16, 2009)	Macular Mapping Test [ Time Frame: One Year ]; Multifocal Electroretinogram [ Time Frame: One Year ]; Central Macular Thickness [ Time Frame: One Year ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Intravitreal Bevacizumab and Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA)
Official Title ICMJE	Intravitreal Bevacizumab and Intravitreal Triamcinolone Associated to Laser Photocoagulation for Diabetic Macular Edema(IBeTA)
Brief Summary	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.
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Diabetic Macular Edema
Intervention ICMJE	Procedure: Laser photocoagulation Focal / grid photocoagulation for diabetic macular edema according to ETDRS guidelines; 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); 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
Study Arms	Active Comparator: Laser Group Focal / grid Laser photocoagulation in diabetic macular edema Intervention: Procedure: Laser photocoagulation; Experimental: Triamcinolone group Intravitreal triamcinolone associated to laser photocoagulation for diabetic macular edema Intervention: Drug: Intravitreal triamcinolone; Experimental: Bevacizumab group Intravitreal Bevacizumab associated to laser photocoagulation for diabetic macular edema Intervention: Drug: Intravitreal bevacizumab
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: October 16, 2009)	12
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	November 2011
Actual Primary Completion Date	November 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Brazil
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00997191
Other Study ID Numbers ICMJE	6826/2009
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Rodrigo Jorge, University of Sao Paulo
Study Sponsor ICMJE	University of Sao Paulo
Collaborators ICMJE	Fundação de Amparo à Pesquisa do Estado de São Paulo
Investigators ICMJE	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
PRS Account	University of Sao Paulo
Verification Date	February 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP