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

NCT03608839 | Completed Phase 2 Results DMC

• 1 other identifier: 003
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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

Conditions

Diabetic Macular Edema

Keywords

Diabetic macular edema; Intravitreal dexamethasone solution; Short term treament

Outcome Measures

Primary Outcomes (1)

• Macular Thickness at 3 Days After Intravitreous Dexamethasone

  Measure macular thickness at 3 days after intravitreous dexamethasone with OCT - unit µm

  Three days after intravitreous dexamethasone

Secondary Outcomes (5)

• Macular Thickness at 28 Days After Intravitreous Dexamethasone

  28 days after intravitreous dexamethasone

• Best Corrected Visual Acuity (BCVA) at 3 Days After Intravitreous Dexamethasone

  Three days after intravitreous dexamethasone

• Best Corrected Visual Acuity (BCVA) at 28 Days After Intravitreous Dexamethasone

  28 days after intravitreous dexamethasone

• Intraocular Pressure (IOP) at 3 Days After Intravitreous Dexamethasone

  3 days after intravitreous dexamethasone

• Intraocular Pressure (IOP) at 28 Days After Intravitreous Dexamethasone

  28 days after intravitreous dexamethasone

Study Arms (3)

0,01ml dexamethasone solution

EXPERIMENTAL

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

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

0,03 ml dexamethasone solution

EXPERIMENTAL

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

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

0,05 ml dexamethasone solution

EXPERIMENTAL

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

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

Interventions

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

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

Also known as: 0,01 ml intravitreous dexamethasone solution

0,01ml dexamethasone solution

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

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

Also known as: 0,03 ml intravitreous dexamethasone solution

0,03 ml dexamethasone solution

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

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

Also known as: 0,05 ml intravitreous dexamethasone solution

0,05 ml dexamethasone solution

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Universidade Federal de Pernambuco: lead

Study Sites (1)

State University of Campinas

Campinas, São Paulo, 13083887, Brazil

Location

Related Publications (11)

• 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.

  PMID: 29127949 BACKGROUND

• 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.

  PMID: 20427088 BACKGROUND

• 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.

  PMID: 21459214 BACKGROUND

• 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.

  PMID: 15790913 BACKGROUND

• 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.

  PMID: 18670086 BACKGROUND

• 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.

  PMID: 21459215 BACKGROUND

• 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.

  PMID: 22330964 BACKGROUND

• 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.

  PMID: 2866759 BACKGROUND

• 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.

  PMID: 20703045 BACKGROUND

• 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.

  PMID: 15078674 BACKGROUND

• 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.

  PMID: 31496644 DERIVED

Limitations and Caveats

The primary limitation of this study was the small number of participants, likely due to the strict inclusion criteria selected.

Results Point of Contact

• Title: Dr Rodrigo Pessoa Cavalcanti Lira
• Organization: State University of Campinas (UNICAMP)

alayf@hotmail.com

551935217396

Study Officials

• Rodrigo PC Lira, MD

  University of Campinas, Brazil

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All the patients were masked. They didn't have acess to the group they belonged. The care provider didn't know the quantity of the drug injected. The outcome assessor was masked as well.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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 (Spectralis; Heidelberg Engineering, Heidelberg, Germany). The randomization schedule was computer generated and stored in a locked cabinet until the study ended. Both patients and the study personnel who collected BCVA, OCT data were masked to the patient study assignment.

Study Record Dates

• First Submitted: July 12, 2018
• First Posted: August 1, 2018
• Study Start: May 1, 2016
• Primary Completion: December 20, 2017
• Study Completion: October 5, 2018
• Last Updated: October 8, 2019
• Results First Posted: October 8, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)