Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration: study protocol for a randomised controlled trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 16; no. 1; p. 85
• Main Authors: Foss, Alexander J E, Childs, Margaret, Reeves, Barnaby C, Empeslidis, Theo, Tesha, Paul, Dhar-Munshi, Sushma, Mughal, Samah, Culliford, Lucy, Rogers, Chris A, Tan, Wei, Montgomery, Alan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10.03.2015; BioMed Central
• Subjects: Age; Angiogenesis inhibitors; Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - adverse effects; Angiogenesis Inhibitors - economics; Antibodies; Bevacizumab - administration & dosage; Bevacizumab - adverse effects; Bevacizumab - economics; Binding sites; Clinical Protocols; Clinical trials; Cost Savings; Cost-Benefit Analysis; Dosage and administration; Drug Administration Schedule; Drug Costs; Drug dosages; Drug therapy; Health aspects; Humans; Hypotheses; Ligands; Macular degeneration; Macular Degeneration - diagnosis; Macular Degeneration - drug therapy; Macular Degeneration - economics; Macular Degeneration - physiopathology; Middle Aged; Monoclonal antibodies; Patients; Physiological aspects; Proportional Hazards Models; Research Design; Risk Factors; Sample Size; State Medicine; Stroke (Disease); Study Protocol; Time Factors; Tomography; Treatment Failure; United Kingdom; Vascular endothelial growth factor; Viral antibodies; Visual acuity; United Kingdom
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-015-0608-2

Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active sites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly longer half-life. These agents have been associated with systemic complications including strokes, so it is desirable to use the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which present a significant challenge both to the hospital services and to the patients (who are elderly). Patients ≥50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received treatment to either eye for the previous six months. We have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention, with patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review. The aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year period. The primary endpoint is time to treatment failure to be analysed using Cox regression. This randomised control trial will show if half dose and two monthly as required is as effective as full dose and monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost and the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the safety profile of this treatment regime. International Standard Randomised Controlled Trial Number: ISRCTN95654194 , registered on 22 September 2009.