Condition category
Eye Diseases
Date applied
19/04/2007
Date assigned
19/04/2007
Last edited
04/08/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Lay summary under review 3

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

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 Treatment with VEGF inhibition can be ‘safely’ withdrawn at 3 months with monthly review to detect CNV reactivation, i.e. criteria for re-starting treatment can be pre-specified to prevent any difference in average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.

On 08/10/2012 the anticipated end date was changed from 31/12/2010 to 30/11/2012.

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

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 Specified

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)2890632224
frances.burns@royalhospitals.n-i.nhs.uk

Sponsor type

Government

Website

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

  1. 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.

  2. 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.

  3. 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.

Additional files

Editorial Notes