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

Alexander J E Foss; Margaret Childs; Barnaby C Reeves; Theo Empeslidis; Paul Tesha; Sushma Dhar-Munshi; Samah Mughal; Lucy Culliford; Chris A Rogers; Wei Tan; Alan Montgomery

doi:10.1186/s13063-015-0608-2

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

Alexander J E Foss, Margaret Childs, Barnaby C Reeves, Theo Empeslidis, Paul Tesha, Sushma Dhar-Munshi, Samah Mughal, Lucy Culliford, Chris A Rogers, Wei Tan, Alan Montgomery

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

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 , registered on 22 September 2009.

Original language	English
Article number	85
Number of pages	9
Journal	Trials
Volume	16
DOIs	https://doi.org/10.1186/s13063-015-0608-2
Publication status	Published - 10 Mar 2015

Research Groups and Themes

BTC (Bristol Trials Centre)
Centre for Surgical Research

Keywords

Age-related macular degeneration
Avastin
Bevacizumab
Trial

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10.1186/s13063-015-0608-2

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This is the final published version of the article (version of record). It first appeared online via BioMed Central at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-0608-2. Please refer to any applicable terms of use of the publisher.
Final published version, 749 KBLicence: CC BY

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ConDuCT-II
Blazeby, J. (Principal Investigator)
1/04/14 → 31/03/19
Project: Research

Cite this

Foss, A. J. E., Childs, M., Reeves, B. C., Empeslidis, T., Tesha, P., Dhar-Munshi, S., Mughal, S., Culliford, L., Rogers, C. A., Tan, W., & Montgomery, A. (2015). Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration: study protocol for a randomised controlled trial. Trials, 16, Article 85. https://doi.org/10.1186/s13063-015-0608-2

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

abstract = "BACKGROUND: Bevacizumab (Avastin{\textregistered}) is as effective as ranibizumab (Lucentis{\textregistered}) 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 , registered on 22 September 2009.",

keywords = "Age-related macular degeneration, Avastin, Bevacizumab, Trial",

author = "Foss, {Alexander J E} and Margaret Childs and Reeves, {Barnaby C} and Theo Empeslidis and Paul Tesha and Sushma Dhar-Munshi and Samah Mughal and Lucy Culliford and Rogers, {Chris A} and Wei Tan and Alan Montgomery",

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TY - JOUR

T1 - Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration

T2 - study protocol for a randomised controlled trial

AU - Foss, Alexander J E

AU - Childs, Margaret

AU - Reeves, Barnaby C

AU - Empeslidis, Theo

AU - Tesha, Paul

AU - Dhar-Munshi, Sushma

AU - Mughal, Samah

AU - Culliford, Lucy

AU - Rogers, Chris A

AU - Tan, Wei

AU - Montgomery, Alan

PY - 2015/3/10

Y1 - 2015/3/10

N2 - 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 , registered on 22 September 2009.

AB - 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 , registered on 22 September 2009.

KW - Age-related macular degeneration

KW - Avastin

KW - Bevacizumab

KW - Trial

U2 - 10.1186/s13063-015-0608-2

DO - 10.1186/s13063-015-0608-2

M3 - Article (Academic Journal)

C2 - 25873213

SN - 1745-6215

VL - 16

JO - Trials

JF - Trials

M1 - 85

ER -

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

Abstract

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Keywords

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