A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation
| ISRCTN | ISRCTN92166560 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN92166560 |
| Protocol serial number | HTA 07/36/01; Sponsor ref: RGHT000449 |
| Sponsor | Royal Group of Hospitals Trust (UK) |
| Funder | Health Technology Assessment Programme |
- Submission date
- 19/04/2007
- Registration date
- 19/04/2007
- Last edited
- 24/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Eye Diseases
Plain English summary of protocol
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
Contact information
Scientific
The Queen's University of Belfast
Centre for Vision Sciences
Institute of Clinical Science
The Royal Hospitals
Grosvenor Rd
Belfast
BT12 6BA
United Kingdom
| Phone | +44 (0)2890 632527 |
|---|---|
| u.chakravarthy@qub.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multi-centre factorial randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation |
| Study acronym | IVAN |
| Study objectives | 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(s) | Health and Personal Social Services 3 in Northern Ireland, ref: 07/NI R03/37 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Bevacizumab, ranibizumub |
| Primary outcome measure(s) |
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. |
| Key secondary outcome measure(s) |
Secondary outcomes will be analysed after one and two years of follow-up, unless otherwise stated. |
| Completion date | 30/11/2012 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 600 |
| Total final enrolment | 610 |
| Key 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. |
| Key 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 |
| Date of first enrolment | 01/07/2007 |
| Date of final enrolment | 30/11/2012 |
Locations
Countries of recruitment
- United Kingdom
- Northern Ireland
Study participating centre
BT12 6BA
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan | Not provided at time of registration |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2012 | Yes | No | |
| Results article | results | 01/07/2012 | Yes | No | |
| Results article | results | 12/10/2013 | Yes | No | |
| Results article | results | 01/12/2013 | Yes | No | |
| Results article | results | 29/07/2014 | Yes | No | |
| Results article | results | 01/10/2015 | Yes | No | |
| Results article | results | 01/12/2016 | Yes | No | |
| Results article | results | 01/02/2018 | Yes | No | |
| Results article | results | 01/01/2019 | Yes | No | |
| Results article | 7-year follow-up | 01/08/2022 | 24/10/2022 | Yes | No |
| Results article | Long-term visual outcomes | 01/09/2020 | 24/10/2022 | Yes | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
24/10/2022: Publication references added.
21/10/2019: The final enrolment number was added from the 2019 results reference.
08/03/2019: Publication references added.
14/04/2016: Publication reference added.
08/10/2012: The overall trial end date was changed from 31/12/2010 to 30/11/2012.
