NCT04991350: REBEL

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

Terminated Phase 4 Last updated 16 February 2023

What this trial tests

Phase 4 trial testing Intravitreal ranibizumab in Diabetic Macular Edema in 5 participants. Terminated before completion.

Timeline

26 November 2021

Primary endpoint
1 September 2022

1 November 2022

Quick facts

Lead sponsor	Cairo University
Phase	Phase 4
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	5
Start date	26 November 2021
Primary completion	1 September 2022
Estimated completion	1 November 2022
Sites	1 location across Egypt

Drugs / interventions tested

• Intravitreal ranibizumab — full drug profile →
• Intravitreal bevacizumab — full drug profile →

Conditions studied

• Diabetic Macular Edema — all drugs for Diabetic Macular Edema →
• Macular Ischemia — all drugs for Macular Ischemia →
• Diabetic Retinopathy — all drugs for Diabetic Retinopathy →
• Vascular Endothelial Growth Factor Overexpression — all drugs for Vascular Endothelial Growth Factor Overexpression →

Sponsor

Cairo University

Who can join

18 and older, any sex, with Diabetic Macular Edema or Macular Ischemia. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Comment on: Disentangling the association between retinal non-perfusion and anti-VEGF agents in diabetic retinopathy.
   Elnahry AG, Yussuf WA. · · 2022 · PMID 34616003 · DOI 10.1038/s41433-021-01800-x