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

Abstract

BackgroundBevacizumab (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/DesignPatients ≥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.DiscussionThis 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 registrationInternational Standard Randomised Controlled Trial Number: ISRCTN95654194, registered on 22 September 2009.

Increased angiogenesis by the rotational muscle flap is crucial for nerve regeneration

“…Avastin is an immunoglobulin G monoclonal antibody directed against VEGF, used for the treatment of cancer and aged-related macular degeneration [24, 32]. In this study, rotational muscle augmented the vascular structures over injured nerves and the associated angiogenesis factor levels.…”

“…In this study, rotational muscle augmented the vascular structures over injured nerves and the associated angiogenesis factor levels. At the same dosage used in macular degeneration [24], intramuscular injection of Avastin attenuated the microvascular structures and angiogenesis factors in the crushed nerve. The up-and-down regulation of angiogenesis factors in the crushed nerve paralleled the increased and decreased nerve regeneration demonstrated in this study, and the results highlight the effects of angiogenesis contributing to nerve regeneration.…”

“…These animals were randomly assigned to various treatment groups, including nerve crush alone (Crush), crush with rotational muscle flap (Crush+MF), and crush with rotational muscle flap and VEGF inhibitors (Avastin treatment) (Crush+MF+Avastin). The intramuscular injection over the rotational muscle flap consisted of 1.25 mg bevacizumab (Avastin) (Roche, Basel, Switzerland) according to the recommended dose for the treatment of the neo-vascular macular degeneration [24]. During the immediate post-procedural period, the animals were monitored closely in the recovery cage until they could maintain sternal recumbency.…”

Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera

“…More frequent dosing, every 2 weeks, has been shown to have greater efficacy. ( 42 , 43 ) A more effective treatment would be for more frequent dosing; however patents will generally not tolerate an every-2-week treatment regime. Non-invasive frequent topical dosing may not reach the high peak levels of an injection, but may provide a constant therapeutic level within the eye.…”

Safety and clinical effectiveness of intravitreal administration of bevacizumab (Lumiere^®) in patients with neovascular age‑related macular degeneration

“…This pharmaceutical form is intended to assure intravitreal injection with minimum risk of contamination and adverse consequences, including endophthalmitis and blindness, associated with reutilization or repackaging of bevacizumab vials for oncological use. Bevacizumab also has the advantage of reducing cost of therapy when compared with other anti-VEGF alternatives, thus helping reduce the financial burden over multiple injections (23)(24)(25).…”