A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation

ISRCTN ISRCTN92166560
DOI https://doi.org/10.1186/ISRCTN92166560
Secondary identifying numbers HTA 07/36/01; Sponsor ref: RGHT000449
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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

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

Prof Usha Chakravarthy
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
Email u.chakravarthy@qub.ac.uk

Study information

Study designMulti-centre factorial randomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleA randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation
Study acronymIVAN
Study objectives1. 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) studiedAge-related macular degeneration (AMD)
InterventionParticipants, 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Bevacizumab, ranibizumub
Primary outcome measureThe 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 measuresSecondary 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 study start date01/07/2007
Completion date30/11/2012

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants600
Total final enrolment610
Key inclusion criteria1. 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 criteria1. 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 enrolment01/07/2007
Date of final enrolment30/11/2012

Locations

Countries of recruitment

  • Northern Ireland
  • United Kingdom

Study participating centre

The Queen's University of Belfast
Belfast
BT12 6BA
United Kingdom

Sponsor information

Royal Group of Hospitals Trust (UK)
Hospital/treatment centre

Royal Research Office
First Floor Education Centre
The Royal Group of Hospitals Trust
Grosvenor Road
Belfast
BT12 6BA
Northern Ireland
United Kingdom

Phone +44 (0)2890 632224
Email frances.burns@royalhospitals.n-i.nhs.uk
ROR logo "ROR" https://ror.org/03rq50d77

Funders

Funder type

Government

Health Technology Assessment Programme
Government organisation / National government
Alternative name(s)
NIHR Health Technology Assessment Programme, HTA
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot 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

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.