Ranibizumab and the Risk of Arterial Thromboembolic Events — RATE  

Coronary Artery Disease Clinical Trial

Official title: Ranibizumab for Age-Related Macular Degeneration and the Risk of Arterial Thromboembolic Events (RATE)

Status Terminated

Clinical Trial Summary

The investigators assume that ranibizumab might be dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well.

Clinical Trial Description

Age-related macular degeneration (AMD) is a degenerative condition affecting the macula or central area of the retina in elderly people. Early AMD is marked by the presence of soft drusen and/or retinal pigment abnormality (hyper- and hypopigmentation). Late AMD includes 2 forms, nonneovascular (dry) AMD and neovascular (wet) AMD. Despite new medical and surgical interventions, AMD remains a leading cause of vision loss in elderly people all over the world.

Ranibizumab is one of the most effective approaches of AMD management. Ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A (VEGF A) — has been evaluated for the treatment of AMD. Ranibizumab binds to the receptor binding site of active forms of VEGF-A. VEGF-A cause neovascularization and leakage in models of ocular angiogenesis and vascular occlusion, and is thought to contribute to the progression of neovascular AMD and macular edema following RVO. Prevents the interaction of VEGF-A with its receptors (VEGFR1 and VEGFR2) on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

There have been a number of studies that have examined a possible association between ranibizumab and arterial thromboembolic events (ATE). The ATE rate in the three controlled neovascular AMD studies during the first year was 1.9% (17 out of 874; 0.3-0.5 mg LUCENTIS) vs 1.1% (5 out of 441) in control arms (AMD-1, AMD-2). In the second year the ATE rate was 2.6% (1323 patients; Lucentis 879) vs Control 444 (p < 0.05). The ATE rate in the two controlled RVO studies (RVO-1, RVO-2) during the first six months was 0.8% (789 patients; Lucentis 527 vs Sham 262).

The investigators assume that ranibizumab can be rather dangerous in patients with history of coronary artery disease or cerebrovascular events. The main objective of study is to reveal contraindications for ranibizumab prescription in patients with history of coronary artery disease and cerebrovascular events. Moreover, an association between management with ranibizumab and ATE rate in healthy above 50 years old persons is a concern of great interest as well. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Screening

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Cerebrovascular Disorders
• Coronary Artery Disease
• Coronary Disease
• Macular Degeneration
• Myocardial Ischemia
• Thromboembolism

• NCT number: NCT01319188
• Study type: Interventional
• Source: Ural Medical University
• Status: Terminated
• Phase: Phase 4
• Start date: June 2010
• Completion date: April 2015