Details of HTA project in progress
Last updated: 30 June 2009 - Next update due: 7 July 2009
Research type: |
Primary Research (e.g. trial) |
Project title: |
A randomised controlled trial (RCT) of alternative treatments to Inhibit VEGF in patients with Age-related choroidal Neovascularisation (IVAN) |
Project ref: |
07/36/01 |
Cost: |
£2,800,119 |
Chief Investigator : |
Professor Usha Chakravarthy, Professor of Ophthalmology and Vision Sciences, Centre for Vision Sciences, The Queen's University of Belfast Trust |
Project Website |
http://www.ivan-trial.co.uk |
Start Date: |
July 2007 |
Publication date: |
Early 2012. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
Choroidal neovascularisation is the growth of blood vessels into in the macular region of the retina of the eye in a condition called wet age-related macular degeneration (AMD). These vessels are leaky and lead to the accumulation of fluid between and within the tissue layers with serious adverse effects on central vision. Lucentis is an 'anti-VEGF' drug which is injected monthly into the eye which causes these blood vessels to stop leaking and shrink. With treatment eyesight improves in a quarter and in the majority (90% or more) eyesight does not deteriorate. This represents a huge improvement over previous treatments. Another anti-VEGF drug, Avastin (from which Lucentis was derived), appears to be equally good and is considerably cheaper but its efficacy and safety have only been studied in case series. We propose a head-to-head trial of Avastin vs. Lucentis to compare their efficacy. We also wish to study whether treatment frequency can be reduced by comparing monthly anti-VEGF treatment for 2 years with monthly anti-VEGF treatment for 3 months only with careful monthly review and re-starting treatment if any signs of disease recur. The study will randomise patients to various combinations of active treatment; there will be no non-treatment group. Eyesight will be assessed at each visit and information collected on quality of life and the costs and burden of illness, which will be compared between the different groups after 1 and 2 years follow-up. Although Lucentis has shown the best result in terms of maintained and improved eyesight of all the AMD treatments, we believe that there are benefits to the patient if we can undertake fewer treatments without compromising eyesight. Patient support organisations agree that this study is important and that there is considerable potential for benefit. UK eye specialists have established a network to study treatments for wet AMD and this network is ideally placed to undertake the study. The trial is expensive as treatment is given monthly and drug costs are high; rigorous assessments are needed and there is also a large trial management component. |
Abstract: |
Wet or neovascular macular degeneration is a condition which causes severe sight loss in older people. Neovascularisation arises in the choroid and breaches the normal anatomical barriers of Bruch's membrane and the retinal pigment epithelium. The complex of new vessels and accompanying inflammatory and glial cells is known as choroidal neovascularisation (CNV). Until recently, available treatments only limited the rate of sight loss with most patients becoming moderately or severely visually impaired in the affected eye despite optimal management. However, very recently a new treatment with a drug known as Lucentis® (Ranibizumab) was found to prevent sight loss in the affected eye in over 90% of recipients when given as intravitreal injections for periods of up to two years. Lucentis® is expensive (approximately £750 per injection) and CNV is common (about 25,000 people with incident CNV per annum in the UK). There is little evidence on which to base criteria for stopping treatment and thus considerable uncertainty about treatment costs. VEGF inhibitors are potent drugs and a recent press release from the manufacturer suggests that Lucentis® (0.5mg) may increase the risk of stroke 4-fold compared to the lower dose (0.3mg) raising concerns about its systemic safety. Another drug, called Avastin® (Bevacizumab) which is licensed for colorectal cancer therapy is similar to Lucentis® in its properties. This drug has also been used to treat neovascular AMD patients and appears to confer similar benefits but the data come from multiple small uncontrolled studies. Avastin® is extremely cheap as the dose for ocular injection is small. Although the large number of small uncontrolled studies and an internet survey which compiled information on several thousand treated patients, have not reported any serious adverse effects, there has been no systematic or robust collection of data on the systemic safety of Avastin®. The present study is therefore a proposal to undertake a prospective randomised controlled clinical trial which will (a) compare the clinical efficacy of the two drugs; (b) compare a reduced treatment regimen versus two years of continuous treatment; (c) describe the cost effectiveness of different drugs and treatment regimens; (d) describe both eye-related and systemic side effects with different drugs and treatment regimens. |
NRR* number, if applicable: |
N0484196285 (*National Research Register) |
ISRCTN* number: | ISRCTN 92166560 (*International Standard Randomised Controlled Trial Number) URL of this project on the Controlled Trials Website: http://www.controlled-trials.com/ISRCTN92166560 |
Project Protocol: |
Project protocol (pdf format, 257 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1625 |
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