ISRCTN - ISRCTN92166560: A randomised controlled trial of alternative treatments to inhibit VEGF in age-related choroidal neovascularisation

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

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details 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 measure

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 (if study stopped)

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

Total final enrolment

610

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 type

Government

Website

Funders

Funder type