Effect of Dexamethasone on Reduction of Macular Thickness in Diabetic Patients, a Randomized Clinical Trial

NCT ID: NCT03608839

Last Updated: 2019-10-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-01
• Study Completion Date: 2018-10-05

Brief Summary

Purpose: To determine the impact of short-term 4mg/ml dexamethasone solution treatment in diabetic macular edema (DME).

Design: Phase II, randomized, prospective, parallel, interventional study.

Participants: Pseudophakic patients with central-involved DME.

Methods: Twenty-seven patients with visual impairment caused by DME were randomized in a 1:1:1 ratio, in order to investigate treatment with 0.01 ml, 0.03 ml and 0.05 ml intravitreous dexamethasone solutions, and followed-up over 28 days

Outcome Measures: The primary outcome was macular thickness at three days after intravitreous dexamethasone. The secondary outcomes were macular thickness at 28 days after intravitreous dexamethasone, best-corrected visual acuity (BCVA) and intraocular pressure (IOP) at three and 28 days after intravitreous dexamethasone

Detailed Description

This is a prospective, phase II, randomized, interventional, monocentric study. Data of consecutive patients with DME who volunteered to participate in the research at the department of ophthalmology of State University of Campinas (UNICAMP) - Brazil between May 2016 and December 2017 were analysed.

At the screening visit, all patients underwent complete ophthalmic evaluation, including best corrected visual acuity (BCVA), slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, fluorescein angiography (Visucam NM/ FA Carl Zeiss; Carl Zeiss Meditec, California, USA), SD- OCT (Spectralis; Heidelberg Engineering, Heidelberg, Germany). Central macular thickness was obtained through 7 horizontal lines ( 30° x 5° area), centered on the fovea, with 1536 A scans per line at 240 µm intervals.

At the baseline study visit, patients were randomized with a 1:1:1 allocation to receive dexamethasone solution 4 mg/ml: 0,01 ml (40 µg) ; or 0,03 ml (120 µg); or 0,05 ml (200 µg). In follow up visits (1, 3, 7, 14, 21, 28 days after) were performed BCVA, slit-lamp biomicroscopy, applanation tonometry, fundus biomicroscopy, SD- OCT.

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

0,01ml dexamethasone solution

One intravitreous injection of 0,01 ml dexamethasone solution 4 mg/ml.

Group Type: EXPERIMENTAL

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,01 ml

Intervention Type: DRUG

0,01 ml intravitreous dexamethasone solution 4mg/ml injection.

0,03 ml dexamethasone solution

One intravitreous injection of 0,03 ml dexamethasone solution 4 mg/ml.

Group Type: EXPERIMENTAL

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,03 ml

Intervention Type: DRUG

0,03 ml intravitreous dexamethasone solution 4mg/ml injection.

0,05 ml dexamethasone solution

One intravitreous injection of 0,05 ml dexamethasone solution 4 mg/ml.

Group Type: EXPERIMENTAL

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,05 ml

Intervention Type: DRUG

0,05 ml intravitreous dexamethasone solution 4mg/ml injection.

Interventions

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,01 ml

0,01 ml intravitreous dexamethasone solution 4mg/ml injection.

Intervention Type: DRUG

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,03 ml

0,03 ml intravitreous dexamethasone solution 4mg/ml injection.

Intervention Type: DRUG

Intravitreous Dexamethasone Solution 4mg/ml - vol 0,05 ml

0,05 ml intravitreous dexamethasone solution 4mg/ml injection.

Intervention Type: DRUG

Other Intervention Names

0,01 ml intravitreous dexamethasone solution; 0,03 ml intravitreous dexamethasone solution; 0,05 ml intravitreous dexamethasone solution

Eligibility Criteria

Inclusion Criteria

• age > = 18 years;
• diagnosis of DM type 2;
• pseudophakic patients
• presence of clinically significant DME according to ETDRS guidelines;
• best correct visual acuity (BCVA) between 20/400 and 20/40;
• central macular thickness (CMT) >= 300 µm measured by spectral domain optical coherence tomography ( Spectralis® Heidelberg). If both eyes of the patient met the elegibility criteria, the eye with worse BCVA at baseline was designated as the study eye.

Exclusion Criteria

• any treatment of DME in the previous 4 months;
• pan retinal photocoagulation (PRP) in the previous 4 months or antecipated need of PRP for the next 6 months;
• any ophthalmologic surgery performed in the previous 4 months;
• history of pars plana vitrectomy;
• history of open-angle glaucoma or intraocular pressure elevation induced by corticosteroids that required anti-glaucomatous treatment or anti- hypertensive ocular treatment;
• intraocular pressure >= 21 mmHg;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade Federal de Pernambuco

OTHER

Sponsor Role: lead

Responsible Party

Rodrigo Pessoa Cavalcanti Lira

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rodrigo PC Lira, MD

Role: STUDY_CHAIR

University of Campinas, Brazil

Locations

State University of Campinas

Campinas, São Paulo, Brazil

Countries

Brazil

References

Maturi RK, Glassman AR, Liu D, Beck RW, Bhavsar AR, Bressler NM, Jampol LM, Melia M, Punjabi OS, Salehi-Had H, Sun JK; Diabetic Retinopathy Clinical Research Network. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2018 Jan 1;136(1):29-38. doi: 10.1001/jamaophthalmol.2017.4914.

Reference Type: BACKGROUND

PMID: 29127949 (View on PubMed)

Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

Reference Type: BACKGROUND

PMID: 20427088 (View on PubMed)

Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033.

Reference Type: BACKGROUND

PMID: 21459214 (View on PubMed)

Tamura H, Miyamoto K, Kiryu J, Miyahara S, Katsuta H, Hirose F, Musashi K, Yoshimura N. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1440-4. doi: 10.1167/iovs.04-0905.

Reference Type: BACKGROUND

PMID: 15790913 (View on PubMed)

Wang K, Wang Y, Gao L, Li X, Li M, Guo J. Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008 Aug;31(8):1541-6. doi: 10.1248/bpb.31.1541.

Reference Type: BACKGROUND

PMID: 18670086 (View on PubMed)

Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A; RESTORE study group. The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):615-25. doi: 10.1016/j.ophtha.2011.01.031.

Reference Type: BACKGROUND

PMID: 21459215 (View on PubMed)

Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS; RISE and RIDE Research Group. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012 Apr;119(4):789-801. doi: 10.1016/j.ophtha.2011.12.039. Epub 2012 Feb 11.

Reference Type: BACKGROUND

PMID: 22330964 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 2866759 (View on PubMed)

Bandello F, Battaglia Parodi M, Lanzetta P, Loewenstein A, Massin P, Menchini F, Veritti D. Diabetic macular edema. Dev Ophthalmol. 2010;47:73-110. doi: 10.1159/000320075. Epub 2010 Aug 10.

Reference Type: BACKGROUND

PMID: 20703045 (View on PubMed)

Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, Taylor HR, Hamman RF; Eye Diseases Prevalence Research Group. The prevalence of diabetic retinopathy among adults in the United States. Arch Ophthalmol. 2004 Apr;122(4):552-63. doi: 10.1001/archopht.122.4.552.

Reference Type: BACKGROUND

PMID: 15078674 (View on PubMed)

Fonseca ALA, Panetta H, Nascimento MA, Lira RPC, Arieta CEL. Effect of intravitreal dexamethasone solution on the reduction of macular thickness in pseudophakic diabetic patients in a public hospital in Brazil: a randomized clinical trial. Clin Ophthalmol. 2019 Aug 9;13:1523-1531. doi: 10.2147/OPTH.S214329. eCollection 2019.

Reference Type: DERIVED

PMID: 31496644 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

003

Identifier Type: -

Identifier Source: org_study_id