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

Foss AJ, Childs M, Reeves BC, Empeslidis T, Tesha P, Dhar-Munshi S, Mughal S, Culliford L, Rogers CA, Tan W, Montgomery A - Trials (2015)

Bottom Line: Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Queen's Medical Centre, Middleton Boulevard, Nottingham, NG7 2UH, England. Alexander.Foss@nottingham.ac.uk.

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.

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Related in: MedlinePlus

Flow diagram for the induction phase of the trial protocol. nAMD: neovascular Age Related Macular Degeneration. PIS: patient information sheet. VA: visual acuity.
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Fig1: Flow diagram for the induction phase of the trial protocol. nAMD: neovascular Age Related Macular Degeneration. PIS: patient information sheet. VA: visual acuity.

Mentions: These hypotheses will be investigated using a two-by-two factorial design. On entry into the trial, all patients will be randomised between standard dose (1.25 mg) or half dose (0.625 mg) of bevacizumab, and review every four to six weeks or every eight to 10 weeks. All patients will initially undergo three-monthly injections, and during this phase the allocated frequency of subsequent review will be masked from doctor and patient. This phase is called the induction phase and is summarised in Figure 1.Figure 1


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

Foss AJ, Childs M, Reeves BC, Empeslidis T, Tesha P, Dhar-Munshi S, Mughal S, Culliford L, Rogers CA, Tan W, Montgomery A - Trials (2015)

Flow diagram for the induction phase of the trial protocol. nAMD: neovascular Age Related Macular Degeneration. PIS: patient information sheet. VA: visual acuity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4376508&req=5

Fig1: Flow diagram for the induction phase of the trial protocol. nAMD: neovascular Age Related Macular Degeneration. PIS: patient information sheet. VA: visual acuity.
Mentions: These hypotheses will be investigated using a two-by-two factorial design. On entry into the trial, all patients will be randomised between standard dose (1.25 mg) or half dose (0.625 mg) of bevacizumab, and review every four to six weeks or every eight to 10 weeks. All patients will initially undergo three-monthly injections, and during this phase the allocated frequency of subsequent review will be masked from doctor and patient. This phase is called the induction phase and is summarised in Figure 1.Figure 1

Bottom Line: Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD).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).

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Queen's Medical Centre, Middleton Boulevard, Nottingham, NG7 2UH, England. Alexander.Foss@nottingham.ac.uk.

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.

Show MeSH
Related in: MedlinePlus