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

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posted on 03.02.2016, 09:50 by A. J. E. Foss, M. Childs, B. C. Reeves, Theo Empeslidis, P. Tesha, S. Dhar-Munshi, S. Mughal, L. Culliford, C. A. Rogers, W. Tan, A. Montgomery
Background 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). Methods/Design 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. Discussion 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. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN95654194 webcite, registered on 22 September 2009.

Funding

The costs for the Bristol Trials Unit were met by the East Midlands Special Commissioning Group (EMSCG). The current running costs for the Nottingham Clinical Trials Unit are currently met by NHS England. The trial was set up to be the major vehicle for delivery of NHS case and accordingly the authors are employed by their respective Hospital Trusts who pay their salaries. Alexander Foss is paid a one PA uplift for running the trial, which is paid from Nottingham University Hospitals who, in turn are commissioned to run the service, initially by EMSCG and now by the clinical commissioning groups.

History

Citation

Trials 2015, 16:85

Version

VoR (Version of Record)

Published in

Trials 2015

Publisher

BioMed Central

issn

1745-6215

eissn

1745-6215

Acceptance date

16/02/2015

Copyright date

2015

Available date

03/02/2016

Publisher version

http://www.trialsjournal.com/content/16/1/85

Language

en

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