Effect of Ranibizumab Versus Bevacizumab on the Macular Perfusion in Diabetic Macular Edema

NCT04991350 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: CU372021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The Early Treatment Diabetic Retinopathy Study (ETDRS) group founded guidelines for treating patients with clinically significant diabetic macular edema (DME) with focal/grid macular laser photocoagulation. Since then, macular laser, and steroids, were the main therapies for the treatment of DME until anti-vascular endothelial growth factors (anti-VEGF) drugs were developed after a growing body of scientific evidence implicated VEGF in the pathophysiologic process of DME. Anti-VEGF drugs have been implicated in the treatment of DME. VEGF has been shown to play an important role in the occurrence of increased vascular permeability in DME. VEGF levels are significantly higher in patients with DME and extensive leakage than in patients with minimal leakage. Many studies such as Diabetic Retinopathy Clinical Research \[DRCR\] Network studies, RESTORE Study, RISE and RIDE Research Group, and The BOLT Study have supported the use of anti-VEGF agents in the treatment of DME with better visual outcomes using anti-VEGF injections alone or in combination with other treatments. Several ocular complications of intravitreal anti-VEGF injections have been reported including endophthalmitis, cataract, and retinal detachment. The different effects on macular perfusion between different anti-VEGFs have yet to be fully concluded with mixed conclusions that it increases or decreases or has no effect on perfusion of the macula in response to Anti-VEGF treatment. In many of these studies, however, patients with more ischemic retinas were not included. Retinal ischemia is a vital factor determining the diabetic retinopathy progression and prognosis. Optical coherence tomography angiography (OCTA) detects blood flow by analyzing signal decorrelation between two sequential OCT cross-sectional scans at the same location. As it detects the movements of red blood corpuscles within the vessels, compared to the stationary retinal surroundings, which will result in signal disparity and imaging The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm improves the signal to noise ratio. OCTA is considered a reliable tool in the detection and quantification of macular ischemia in diabetics. In this study, the investigators aim to compare the effect of repeated intravitreal injections of ranibizumab and bevacizumab on the perfusion of different capillary layers in the macula of diabetic patients using OCTA.

Conditions

Diabetic Macular Edema; Macular Ischemia; Diabetic Retinopathy; Vascular Endothelial Growth Factor Overexpression

Keywords

Diabetic macular edema; Macular perfusion; Optical coherence tomography angiography; Anti-VEGF

Outcome Measures

Primary Outcomes (3)

• Change in foveal avascular zone area

  The change in the foveal avascular zone area will be compared between the two treatment arms as a measure of macular perfusion change.

  0 and 3 months.

• Change in vascular density of the superficial retinal capillary plexus

  The change in the superficial retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change.

  0 and 3 months.

• Change in vascular density of the deep retinal capillary plexus

  The change in the deep retinal capillary plexus vascular density will be compared between the two treatment arms as a measure of macular perfusion change.

  0 and 3 months.

Secondary Outcomes (4)

• Change in best corrected visual acuity

  0 and 3 months

• Change in central macular thickness

  0 and 3 months

• Change in intraocular pressure

  0 and 3 months

• Change of severity of diabetic retinopathy

  0 and 3 months

Study Arms (2)

Ranibizumab Group

ACTIVE COMPARATOR

Patients will receive monthly ranibizumab injections for 3 months.

Drug: Intravitreal ranibizumab

Bevacizumab Group

ACTIVE COMPARATOR

Patients will receive monthly bevacizumab injections for 3 months.

Drug: Intravitreal bevacizumab

Interventions

Intravitreal ranibizumab DRUG

Intravitreal injection of 0.3 mg/0.05 ml ranibizumab will be performed monthly for 3 months.

Also known as: Lucentis

Ranibizumab Group

Intravitreal bevacizumab DRUG

Intravitreal injection of 1.25 mg/0.05 ml bevacizumab will be performed monthly for 3 months.

Also known as: Avastin

Bevacizumab Group

Eligibility Criteria

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

You may qualify if:

• Patients ≥18 years old with type 1 or 2 diabetes mellitus with decreased BCVA due to center involving diabetic macular edema on spectral-domain optical coherence tomography.
• Patients with central macular thickness "CMT" of ≥ 300 micrometers

You may not qualify if:

• Ocular conditions that may affect macular perfusion (e.g. retinal vascular diseases, uveitis, vasculitis etc.)
• History of vitreo-retinal surgeries.
• Previous macular laser treatment
• Presence of epi-retinal membrane involving the macula or vitreo-macular traction.
• Media opacity preventing good image quality.
• Uncontrolled glaucoma.
• Thrombo-embolic events within 6 months
• Previous intravitreal injections of anti-VEGF

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, 11956, Egypt

Location

Related Publications (8)

• Michaelides M, Kaines A, Hamilton RD, Fraser-Bell S, Rajendram R, Quhill F, Boos CJ, Xing W, Egan C, Peto T, Bunce C, Leslie RD, Hykin PG. A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data: report 2. Ophthalmology. 2010 Jun;117(6):1078-1086.e2. doi: 10.1016/j.ophtha.2010.03.045. Epub 2010 Apr 22.

  PMID: 20416952 BACKGROUND

• Manousaridis K, Talks J. Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease? Br J Ophthalmol. 2012 Feb;96(2):179-84. doi: 10.1136/bjophthalmol-2011-301087.

  PMID: 22250209 BACKGROUND

• Elnahry AG, Abdel-Kader AA, Raafat KA, Elrakhawy K. Evaluation of the Effect of Repeated Intravitreal Bevacizumab Injections on the Macular Microvasculature of a Diabetic Patient Using Optical Coherence Tomography Angiography. Case Rep Ophthalmol Med. 2019 Apr 18;2019:3936168. doi: 10.1155/2019/3936168. eCollection 2019.

  PMID: 31139483 RESULT

• Elnahry AG, Abdel-Kader AA, Raafat KA, Elrakhawy K. Evaluation of Changes in Macular Perfusion Detected by Optical Coherence Tomography Angiography following 3 Intravitreal Monthly Bevacizumab Injections for Diabetic Macular Edema in the IMPACT Study. J Ophthalmol. 2020 Apr 27;2020:5814165. doi: 10.1155/2020/5814165. eCollection 2020.

  PMID: 32411431 RESULT

• Elnahry AG, Abdel-Kader AA, Habib AE, Elnahry GA, Raafat KA, Elrakhawy K. Review on Recent Trials Evaluating the Effect of Intravitreal Injections of Anti-VEGF Agents on the Macular Perfusion of Diabetic Patients with Diabetic Macular Edema. Rev Recent Clin Trials. 2020;15(3):188-198. doi: 10.2174/1574887115666200519073704.

  PMID: 32427087 RESULT

• Elnahry AG, Elnahry GA. Optical Coherence Tomography Angiography of Macular Perfusion Changes after Anti-VEGF Therapy for Diabetic Macular Edema: A Systematic Review. J Diabetes Res. 2021 May 22;2021:6634637. doi: 10.1155/2021/6634637. eCollection 2021.

  PMID: 34124270 RESULT

• Elnahry AG, Ramsey DJ. Automated Image Alignment for Comparing Microvascular Changes Detected by Fluorescein Angiography and Optical Coherence Tomography Angiography in Diabetic Retinopathy. Semin Ophthalmol. 2021 Nov 17;36(8):757-764. doi: 10.1080/08820538.2021.1901122. Epub 2021 Mar 30.

  PMID: 33784213 RESULT

• Sorour OA, Elsheikh M, Chen S, Elnahry AG, Baumal CR, Pramil V, Abdelhalim TI, Nassar E, Moult EM, Witkin AJ, Duker JS, Waheed NK. Mean macular intercapillary area in eyes with diabetic macular oedema after anti-vascular endothelial growth factor therapy and its association with treatment response. Clin Exp Ophthalmol. 2021 Sep;49(7):714-723. doi: 10.1111/ceo.13966. Epub 2021 Aug 1.

  PMID: 34189816 RESULT

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Ranibizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Ayman G Elnahry, MD, PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Karim M Abdelaty, MBBCH

  National Eye Center

  STUDY DIRECTOR

• Ahmed A Abdel-Kader, MD, PhD

  Cairo University

  STUDY CHAIR

• Ahmed A Mohalhal, MD, PhD

  Cairo University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Ophthalmology

Study Record Dates

• First Submitted: July 24, 2021
• First Posted: August 5, 2021
• Study Start: November 26, 2021
• Primary Completion: September 1, 2022
• Study Completion: November 1, 2022
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)