Plain English Summary
Background and study aims
Wet or neovascular age-related macular degeneration (AMD) is a condition which causes severe sight loss in older people. This condition is due to new blood vessel growing into the central region of the retina of the eye, known as choroidal neovascularisation (CNV). These vessels are leaky and lead to the accumulation of fluid between and within the layers of the retina with serious adverse effects on central vision. Lucentis® is an 'anti-VEGF' drug which is injected monthly into the eye and causes these blood vessels to stop leaking and to shrink. With treatment, eyesight improves in a quarter of affected people and, in the majority (90% or more) eyesight does not deteriorate over two years. These results represent a major improvement over previous treatments. Another anti-VEGF drug, Avastin® (from which Lucentis was derived), may be equally good and is considerably less expensive, but its effectiveness and safety need to be confirmed. This study is a head-to-head comparison of the effectiveness and safety of Avastin® and Lucentis®. We are also studying whether the number of treatments needed 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.
Who can participate?
Adults aged 50 and over with CNV caused by AMD.
What does the study involve?
Patients are randomly allocated to various combinations of active treatment. Their eyesight is assessed at each visit and information is collected on their 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.
What are the possible benefits and risks of participating?
Although Lucentis has so far shown the best results of all the licensed anti-VEGF treatments in terms of maintained and improved eyesight, we believe that there will be benefits to patients if we can undertake fewer treatments without compromising eyesight. Patient support organisations agree that this study is important and that it has considerable potential to benefit future patients.
Where is the study run from?
The Queen's University of Belfast (UK)
When is the study starting and how long is it expected to run for?
July 2007 to November 2012
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)
Who is the main contact?
Prof Usha Chakravarthy
u.chakravarthy@qub.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Prof Usha Chakravarthy
ORCID ID
Contact details
The Queen's University of Belfast
Centre for Vision Sciences
Institute of Clinical Science
The Royal Hospitals
Grosvenor Rd
Belfast
BT12 6BA
United Kingdom
+44 (0)2890 632527
u.chakravarthy@qub.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
HTA 07/36/01; Sponsor ref: RGHT000449
Study information
Scientific title
A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation
Acronym
IVAN
Study hypothesis
1. Avastin® (bevacizumab) is not inferior to Lucentis® (ranibizumub) with respect to the benefits of vascular endothelial growth factor (VEGF) inhibition in maintaining/improving visual acuity in eyes with chorodial neovascularisation (CNV).
2. Treatment with VEGF inhibition can be 'safely' withdrawn at 3 months with monthly review to detect CNV reactivation, i.e. criteria for re-starting treatment can be pre-specified to prevent any difference in average visual acuity compared with continuing monthly treatment.
More details can be found at http://www.nets.nihr.ac.uk/projects/hta/073601
Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/51780/PRO-07-36-01.pdf
Ethics approval
Health and Personal Social Services 3 in Northern Ireland, ref: 07/NI R03/37
Study design
Multi-centre factorial randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Age-related macular degeneration (AMD)
Intervention
Participants, clinical staff and researchers will be masked to allocation of VEGF inhibition drug but not to stopping/continuing treatment at three months.
Factor 1: Intravitreal injection using either Avastin® or Lucentis® (VEGF inhibition drugs).
Factor 2: Intravitreal injection of VEGF inhibition drug, either monthly for 2 years or monthly for 3 months with subsequent monthly review to detect CNV reactivation.
Intervention type
Drug
Phase
Not Applicable
Drug names
Bevacizumab, ranibizumub
Primary outcome measures
The primary outcome is corrected 1 metre VAlogMAR, measured as the number of letters read on a standard ETDRS chart. The primary end point will be VAlogMAR after two years of follow-up.
Secondary outcome measures
Secondary outcomes will be analysed after one and two years of follow-up, unless otherwise stated.
1. Frequencies of adverse effects of treatment
2. Generic and vision-specific health-related quality of life (HRQoL)
3. Treatment satisfaction
4. Cumulative resource use/cost, and cost-effectiveness
5. Clinical measures of vision
6. CNV morphology (from masked grading of fundus fluorescein angiograms [FFA] and optical coherence tomography scans [OCTs]).
7. Distance VAlogMAR after all patients have been followed for 1 year after starting treatment.
8. Survival free from treatment failure (i.e. satisfying one or more of the criteria for re-treatment).
Overall trial start date
01/07/2007
Overall trial end date
30/11/2012
Reason abandoned
Eligibility
Participant inclusion criteria
1. Adults age ≥50 of either sex
2. Newly referred for the treatment of CNV caused by Age-related Macular Degeneration (AMD) in the first or second eye
3. Corrected 1 metre logarithmic minimal angle resolution visual acuity (VAlogMAR) ≥25 letters read on a standard Early Treatment Diabetic Retinopathy Study (ETDRS) chart
4. CNV involving the centre of the fovea
If a fellow eye develops CNV from AMD, it will be treated with the optimal locally available treatment.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
600
Participant exclusion criteria
1. Corrected 1 metre VAlogMAR <25 letters
2. Long standing CNV evidenced by the presence of fibrosis in excess of 50% of the total lesion
3. Presence of other active ocular disease causing concurrent vision loss, e.g. diabetic retinopathy
4. Previous treatment with PhotoDynamic Therapy (PDT) or a VEGF inhibitor in the eye being considered for inclusion
Recruitment start date
01/07/2007
Recruitment end date
30/11/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Queen's University of Belfast
Belfast
BT12 6BA
United Kingdom
Sponsor information
Organisation
Royal Group of Hospitals Trust (UK)
Sponsor details
Royal Research Office
First Floor Education Centre
The Royal Group of Hospitals Trust
Grosvenor Road
Belfast
BT12 6BA
United Kingdom
+44 (0)2890 632224
frances.burns@royalhospitals.n-i.nhs.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Health Technology Assessment Programme
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22555112
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23870813
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25079928
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26445075
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/27073205
Publication citations
-
Results
, Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, Toth C, Redford M, Ferris FL, Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results., Ophthalmology, 2012, 119, 7, 1388-1398, doi: 10.1016/j.ophtha.2012.03.053.
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Results
Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, Reeves BC, , Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial., Lancet, 2013, 382, 9900, 1258-1267, doi: 10.1016/S0140-6736(13)61501-9.
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Results
Dakin HA, Wordsworth S, Rogers CA, Abangma G, Raftery J, Harding SP, Lotery AJ, Downes SM, Chakravarthy U, Reeves BC, , Cost-effectiveness of ranibizumab and bevacizumab for age-related macular degeneration: 2-year findings from the IVAN randomised trial., BMJ Open, 2014, 4, 7, e005094, doi: 10.1136/bmjopen-2014-005094.
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Results
Chakravarthy U, Harding SP, Rogers CA, Downes S, Lotery AJ, Dakin HA, Culliford L, Scott LJ, Nash RL, Taylor J, Muldrew A, Sahni J, Wordsworth S, Raftery J, Peto T, Reeves BC, A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN), Health Technol Assess, 2015, 19, 78, 1-298.
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Results
Br J Ophthalmol, Changes in intraocular pressure in study and fellow eyes in the IVAN trial, 2016, doi: 10.1136/bjophthalmol-2015-307595.