Effects of Intravitreal Ranibizumab for Macular Edema With Nonproliferative Diabetic Retinopathy

NCT02834663 | Completed Phase 4 Results

• 1 other identifier: CRFB002DKR03T
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

Title of study: Effects of Ranibizumab to delay or regression non-proliferative diabetic retinopathy(NPDR) with DME assessed by microaneurysm changes: A pilot study Objectives Diabetic retinopathy (DR) is a major cause of visual impairment. Anti-vascular endothelial growth factors have demonstrated therapeutic benefits in diabetic macular edema (DME). We aimed to prospectively analyze the effects of early intensive treatment using intravitreal ranibizumab (IVR) injections in nonproliferative diabetic retinopathy patients with macular edema. Primary objective: To investigate other efficacy endpoints including other visual acuity, anatomical change in mild-to-moderate NPDR with DME after intravitreal Ranibizumab injection from baseline through 6 months after treatment. Secondary objectives: To compare microvascular changes assessed by microaneurysm counts and perifoveal non-perfusion area changes and safty in eyes of mild-to-moderate NPDR with DME after intravitreal Ranibizumab injection from baseline through 6 months after treatment.

Conditions

Nonproliferative Diabetic Retinopathy

Keywords

Nonproliferative diabetic retinopathy, Microaneurysms

Outcome Measures

Primary Outcomes (2)

• The Best Corrected Visual Acuity (BCVA)

  BCVA was performed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at baseline and 6 months. The BCVA compare the degree of improvement or worsening of vision at baseline and 6 months. (value at 6 months minus value at baseline)

  6 months

• Central Macular Thickness(CMT)

  CRT was performed using OCT at each visit. The OCT measured at each visit was analyzed statistically. the CMT compare the degree of improvement or worsening of vision at baseline and 6 months. (value at 6 months minus value at baseline)

  6 months

Secondary Outcomes (6)

• The Total Number of Microaneurysm

  6 months

• The Microaneurysm Formation Rate

  6 months

• The Microaneurysm Disappearance Rate

  6 months

• The Microaneurysm Turnover

  6 months

• Perifoveal Non-perfusion Area in FAG (mm²)

  6 months

Study Arms (1)

Lucentis

EXPERIMENTAL

Patients were administered 0.5-mg IVR injections monthly for 6 months.

Drug: Lucentis

Interventions

Lucentis DRUG

Local anesthesia with T-caine with Saline irrigation. Routine eye drap was done by potadine-cotton ball. Lucentis injected to vitreous cavity, finally dressing.

Also known as: Intravitreal Lucentis injection

Lucentis

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (Male \& female) ≥40 years of age
• Type 2 DM
• Best corrected visual acuity ≥ 20/200 (Snellen equivalent using Early Treatment Diabetic Retinopathy Study chart)
• central retinal thickness of ≥300 µm on optical coherence tomography
• nonproliferative diabetic retinopathy (NPDR) with diabetic macular edema

You may not qualify if:

• proliferative diabetic retinopathy
• Vitreous hemorrhage
• previous history of vitreoretinal surgery, post-cataract operation status (≤4 months before participation in this study)
• prior treatment with anti-VEGF drugs, intraocular corticosteroids, and/or retinal laser application
• Uncontrolled hypertension.
• Uncontrolled glaucoma.

Sponsors & Collaborators

• Wonkwang University Hospital: lead
• Novartis Korea Ltd.: collaborator

Related Publications (19)

• Liinamaa MJ, Savolainen MJ. High vitreous concentration of vascular endothelial growth factor in diabetic patients with proliferative retinopathy using statins. Ann Med. 2008;40(3):209-14. doi: 10.1080/07853890701749209.

  PMID: 18382886 BACKGROUND

• Noma H, Funatsu H, Yamasaki M, Tsukamoto H, Mimura T, Sone T, Hirayama T, Tamura H, Yamashita H, Minamoto A, Mishima HK. Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion. Eye (Lond). 2008 Jan;22(1):42-8. doi: 10.1038/sj.eye.6702498. Epub 2006 Jul 7.

  PMID: 16826241 BACKGROUND

• Crawford TN, Alfaro DV 3rd, Kerrison JB, Jablon EP. Diabetic retinopathy and angiogenesis. Curr Diabetes Rev. 2009 Feb;5(1):8-13. doi: 10.2174/157339909787314149.

  PMID: 19199892 BACKGROUND

• Usui T, Ishida S, Yamashiro K, Kaji Y, Poulaki V, Moore J, Moore T, Amano S, Horikawa Y, Dartt D, Golding M, Shima DT, Adamis AP. VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. Invest Ophthalmol Vis Sci. 2004 Feb;45(2):368-74. doi: 10.1167/iovs.03-0106.

  PMID: 14744874 BACKGROUND

• Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80. doi: 10.1124/pr.56.4.3.

  PMID: 15602010 BACKGROUND

• Roy S, Ha J, Trudeau K, Beglova E. Vascular basement membrane thickening in diabetic retinopathy. Curr Eye Res. 2010 Dec;35(12):1045-56. doi: 10.3109/02713683.2010.514659. Epub 2010 Oct 7.

  PMID: 20929292 BACKGROUND

• Hammes HP. Pericytes and the pathogenesis of diabetic retinopathy. Horm Metab Res. 2005 Apr;37 Suppl 1:39-43. doi: 10.1055/s-2005-861361.

  PMID: 15918109 BACKGROUND

• Stitt AW, Gardiner TA, Archer DB. Histological and ultrastructural investigation of retinal microaneurysm development in diabetic patients. Br J Ophthalmol. 1995 Apr;79(4):362-7. doi: 10.1136/bjo.79.4.362.

  PMID: 7742285 BACKGROUND

• Ribeiro ML, Nunes SG, Cunha-Vaz JG. Microaneurysm turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild nonproliferative diabetic retinopathy. Diabetes Care. 2013 May;36(5):1254-9. doi: 10.2337/dc12-1491. Epub 2012 Nov 30.

  PMID: 23204247 BACKGROUND

• Haritoglou C, Kernt M, Neubauer A, Gerss J, Oliveira CM, Kampik A, Ulbig M. Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy. Retina. 2014 Jan;34(1):157-64. doi: 10.1097/IAE.0b013e318295f6de.

  PMID: 23792485 BACKGROUND

• Sjolie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Aldington S, Chaturvedi N. Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme. Diabet Med. 2011 Mar;28(3):345-51. doi: 10.1111/j.1464-5491.2010.03210.x.

  PMID: 21309844 BACKGROUND

• Kohner EM, Sleightholm M. Does microaneurysm count reflect severity of early diabetic retinopathy? Ophthalmology. 1986 May;93(5):586-9. doi: 10.1016/s0161-6420(86)33692-3.

  PMID: 3725317 BACKGROUND

• Nunes S, Pires I, Rosa A, Duarte L, Bernardes R, Cunha-Vaz J. Microaneurysm turnover is a biomarker for diabetic retinopathy progression to clinically significant macular edema: findings for type 2 diabetics with nonproliferative retinopathy. Ophthalmologica. 2009;223(5):292-7. doi: 10.1159/000213639. Epub 2009 Apr 16.

  PMID: 19372723 BACKGROUND

• Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981 Jul;88(7):583-600.

  PMID: 7196564 BACKGROUND

• Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004 May;3(5):391-400. doi: 10.1038/nrd1381. No abstract available.

  PMID: 15136787 BACKGROUND

• Han XX, Guo CM, Li Y, Hui YN. Effects of bevacizumab on the neovascular membrane of proliferative diabetic retinopathy: reduction of endothelial cells and expressions of VEGF and HIF-1alpha. Mol Vis. 2012;18:1-9. Epub 2012 Jan 1.

  PMID: 22232563 BACKGROUND

• Leicht SF, Kernt M, Neubauer A, Wolf A, Oliveira CM, Ulbig M, Haritoglou C. Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment. Ophthalmologica. 2014;231(4):198-203. doi: 10.1159/000357505. Epub 2014 Mar 19.

  PMID: 24662930 BACKGROUND

• Kohner EM, Stratton IM, Aldington SJ, Turner RC, Matthews DR. Microaneurysms in the development of diabetic retinopathy (UKPDS 42). UK Prospective Diabetes Study Group. Diabetologia. 1999 Sep;42(9):1107-12. doi: 10.1007/s001250051278.

  PMID: 10447523 BACKGROUND

• Horii T, Murakami T, Nishijima K, Sakamoto A, Ota M, Yoshimura N. Optical coherence tomographic characteristics of microaneurysms in diabetic retinopathy. Am J Ophthalmol. 2010 Dec;150(6):840-8. doi: 10.1016/j.ajo.2010.06.015. Epub 2010 Sep 19.

  PMID: 20855054 BACKGROUND

MeSH Terms

Conditions

Microaneurysm

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Aneurysm; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Seung Joon Lee
• Organization: Wonkwang University Hospital

eunilsa@hanmail.net

010-5004-8165

Study Officials

• Yunsik Yang, MD, Ph D

  Department of Ophthalmology, Wonkwang University School of Medicine

  STUDY CHAIR

• Seungjoon Lee, MD, Ph D

  Study Official Affiliation should have no more than 80 characters.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 26, 2016
• First Posted: July 15, 2016
• Study Start: August 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: December 1, 2019
• Last Updated: May 22, 2020
• Results First Posted: April 22, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share