Condition category
Eye Diseases
Date applied
26/11/2014
Date assigned
26/11/2014
Last edited
12/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
The retina is a light-sensitive layer at the back of the eye. It has a blood supply that provides oxygen and nutrients. Blood drains from the retina and leaves the eye through the central retinal vein. Blockage of the central retinal vein (CRVO) leads to fluid accumulating in part of the retina called the macula (macular oedema [MO]). This reduces the eye’s ability to distinguish the details and shapes of objects (visual acuity). Until 3 years ago no treatment improved visual acuity in MO due to CRVO. The drugs ranibizumab and aflibercept are effective at improving visual function in patients with MO due to CRVO and cause relatively few side effects. Aflibercept may have a longer duration of action than ranibizumab but there is no data on the comparison for this condition. Bevacizumab, similar to ranibizumab, has been shown to be as good as ranibizumab for another eye disease, wet macular degeneration, and is significantly cheaper. Its use in MO due to CRVO would result in very significant NHS cost savings. However, more data is required to support its routine use for this condition in the NHS. This study will determine whether bevacizumab and aflibercept are as effective as ranibizumab at improving visual function in MO due to CRVO and sufficiently cost effective to merit their use.

Who can participate?
Patients aged over 18 with MO due to CRVO

What does the study involve?
Participants are randomly allocated to be treated with either bevacizumab, aflibercept or ranibizumab injected into the eye, and are followed up for 2 years.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
The study will take place in approximately 50 Ophthalmology Centres in the UK and will be managed by the King’s Clinical Trials Unit.

When is the study starting and how long is it expected to run for?
December 2014 to May 2018

Who is funding the study?
NIHR CEAT Programme (UK)

Who is the main contact?
Mr Philip Hykin

Trial website

Contact information

Type

Scientific

Primary contact

Mr Philip Hykin

ORCID ID

Contact details

Moorfields Eye Hospital
London
EC1V 2PD
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

17808

Study information

Scientific title

A multicentre Phase III double-masked randomised controlled non-inferiority trial comparing the clinical and cost effectiveness of intravitreal therapy with ranibizumab (Lucentis) vs aflibercept (Eylea) vs bevacizumab (Avastin) for macular oedema due to central retinal vein occlusion

Acronym

LEAVO

Study hypothesis

The primary hypothesis is that bevacizumab and aflibercept are as effective as ranibizumab in reducing visual loss from macular odema due to central retinal vein occlusion.

More details can be found here: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=17808

Ethics approval

Ref: 14/LO/1043

Study design

Multicentre Phase III double-masked randomised controlled non-inferiority trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Macula odema due to central retinal vein occlusion

Intervention

Intravitreal aflibercept and bevacizumab versus intravitreal ranibizumab

Intervention type

Drug

Phase

Phase III

Drug names

Aflibercept, bevacizumab, ranibizumab

Primary outcome measures

Change in best corrected visual acuity from baseline to 100 weeks in the study eye measured in ETDRS letter score at 4 metres: difference in means between bevacizumab and ranibizumab and between aflibercept and ranibizumab

Secondary outcome measures

1. Clinical effectiveness: multiple additional visual acuity and anatomical outcomes
2. Cost effectiveness outcomes

Overall trial start date

01/12/2014

Overall trial end date

01/05/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Subjects of either sex aged ≥ 18 years
2. Clinical diagnosis of centre-involving macular oedema (MO) due to CRVO
3. CRVO of ≤ 12 months duration
4. Best corrected visual acuity in the study eye ≥ 19 and ≤ 73 ETDRS letters (approximate Snellen VA 3/60 to VA 6/12)
5. Best corrected visual acuity in the non-study eye ≥ 14 ETDRS letters (approximate Snellen VA ≥ 2/60).
6. SD-OCT central subfield thickness (CST) > 320μm (Spectralis) predominantly due to MO secondary to CRVO in the study eye. See appendix 1 for equivalent CST value for alternative SD-OCT machines.
7. Media clarity, pupillary dilatation and subject cooperation sufficient for adequate fundus imaging of the study eye
8. In cases of bilateral CRVO, if both eyes are potentially eligible, unless the patient prefers otherwise the worst seeing eye will be recruited

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

459

Participant exclusion criteria

The following apply to the study eye only and to the non-study eye only where specifically stated:
1. Macular oedema considered to be due to a cause other than CRVO (e.g. diabetic macular oedema, Irvine-Gass syndrome).
2. An ocular condition is present that, in the opinion of the investigator, might affect macular oedema or alter visual acuity during the course of the study (e.g. vitreomacular traction)
3. Any previously documented diabetic retinopathy or diabetic macular oedema in the study eye.
4. Moderate or severe non proliferative diabetic retinopathy (NPDR) or quiescent, treated or active proliferative diabetic retinopathy (PDR) or macular oedema in the non-study eye. Note: Mild NPDR only is permissible in the non-study eye.
5. History of treatment for MO due to CRVO in the past 90 days with intravitreal or peribulbar corticosteroids or in the last 60 days with anti-VEGF drugs or >3 prior anti-VEGF treatments in the previous 12 months.
6. Active iris or angle neovascularisation, neovascular glaucoma, untreated NVD, NVE and vitreous haemorrhage or treatment for these conditions in the last 3 months.
7. Uncontrolled glaucoma [>30mmHg], either untreated or on anti-glaucoma medication at screening.
8. Any active periocular or intraocular infection or inflammation (e.g. conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis).

Systemic exclusion criteria:
9. Uncontrolled blood pressure defined as a systolic value > 170mmHg and diastolic value > 110mmHg.
10. Myocardial infarction, stroke, transient ischaemic attack, acute congestive cardiac failure or any acute coronary
event < 3 months before randomisation
11. Women of child bearing potential unless using effective methods of contraception throughout the study and for 6 months after their last injection for the trial. Effective contraception is defined as one of the following:
11.1. Barrier method: condoms or occlusive cap with spermicides
11.2. True abstinence: When it is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
11.3. Have had tubal ligation or bilateral oophorectomy (with or without hysterectomy)
11.4. Male partner sterilisation. The vasectomised male partner should be the only partner for the female participant
11.5. Use of established oral, injected or implanted hormonal methods of contraception and intrauterine device
12. Pregnant or lactating women.
13. Males who do not agree to an effective form of contraception for the duration of the study and for 6 months after their last injection for the trial
14. Hypersensitivity to the active ingredients aflibercept, bevacizumab or ranibizumab or any of the excipients of these drugs
15. Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
16. A condition that, in the opinion of the investigator, would preclude participation in the study.
17. Participation in an investigational trial involving an investigational medicinal product within 90 days of randomisation

Recruitment start date

01/12/2014

Recruitment end date

01/05/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Moorfields Eye Hospital
London
EC1V2PD
United Kingdom

Sponsor information

Organisation

Moorfields Eye Hospital (UK)

Sponsor details

City Road
London
EC1V 2PD
United Kingdom

Sponsor type

Hospital/treatment centre

Website

www.moorfields.nhs.uk

Funders

Funder type

Government

Funder name

NIHR CEAT Programme: Ref No: 11/92/03

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

N/A

Publication citations

Additional files

Editorial Notes

12/02/2016: Plain English summary added.