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Trial registered on ANZCTR

Registration number

ACTRN12615001094561

Ethics application status

Approved

Date submitted

6/10/2015

Date registered

19/10/2015

Date last updated

28/07/2024

Date data sharing statement initially provided

23/01/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

The combination treatment of laser bypass (chorioretinal venous anastomosis) and Lucentis for the treatment of macula oedema (swelling at the back of the eye) that has occurred as a result of a central retinal vein occlusion, compared to the published results of Lucentis treatment only.

Scientific title

The combination treatment of laser induced chorioretinal venous anastomosis and Lucentis for macula oedema that is secondary to central retinal vein occlusion, compared to the published results of Lucentis treatment only, a phase IV study.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1175-0486

Trial acronym

L-CVBS Extension Study

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Maucula oedema secondary to central retinal vein occlusion.

Condition category

Condition code

Eye

Diseases / disorders of the eye

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Study participants will receive a combination treatment of laser bypass (chorioretinal venous anastomosis, L-CRA) and intraocular injections of Lucentis. Both treatments are approved for this condition. This is a phaseIV study that follows on from the L-CVBS study (ACTRN12612000004864). The laser L-CRA treatment will occur first, with the Lucentis injections commencing 4-5 weeks later.

The Ellex Integre S laser will be used to create the anastomosis. Two sites will be chosen, one above and one below the optic disc. Both will be over a tributary of a major quadratic vein at least 2 disc diameters away from the optic disc. It is not possible to be specific about the location as this will depend on the individual anatomical arrangement in each participant's eye. The spot size is 50um whilst the power will be up to 4W (depends on the degree of cataract), and duration of 0.1 seconds. There is only one laser treatment session that consists of two attempts to establish a functional L-CRA.

Following the L-CRA treatment, participants will commence monthly injections of Lucentis (Ranibizumab). Lucentis is a TGA approved treatment for this condition, and has recently been placed on the PBS. The Lucentis will be obtained through the PBS authority by the investigator. The dose for each intravitreal injection is 2.3mg/0.23mL(10mg/mL) solution, the volume injected is 50ul. There will be a loading dose of three injections, each at 4 week intervals. Participants will be monitored monthly until Month 6. and if during this time the participant's visual acuity drops and/or the oedema has returns, Lucentis treatment will continue (at monthly intervals) until the visual acuity and/or oedema stabilises. From Month 6- Month 12, the visits will occur once every 2 months, provided the participant's visual acuity is stable and there is no macula oedema. If an injection occurs, then the visits revert back to monthly until visual acuity and macula oedema stabilise. Likewise, in the second year of the study, visits may occur once every 3 months if visual acuity and macula oedema are stable, but if there is a drop in visual acuity and/or macula oedema returns, monthly Lucentis injections will resume until visual acuity and/or the oedema stablises. Visits may then gradually move to once very 2 months and then once every three months. In summary, participants receive 3 Lucentis injections at monthly intervals (loading dose) and then further Lucentis treatment will only be administered if visual acuity drops and/or macula oedema returns. The study duration is 2 years.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Devices

Comparator / control treatment

There is no control group for this study.
The number of injections required by the participants in this study after the loading dose of Lucentis will be compared to the published results where the only treatment is Lucentis.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Compare the number of injections required in the combination treatment of laser bypass (L-CRA) and Lucentis in this study to published studies using monotherapy Lucentis (CRUISE, HORIZON and RETAIN studies).

Timepoint [1]

Month 24 after the L-CRA treatment.

Secondary outcome [1]

Mean average best visual acuity (BCVA) from baseline to months 6, 12 and 24 between the combination treatment group and previously reported data using Lucentis treatment alone.

Timepoint [1]

Baseline, Month 6, Month 12 and Month 24 after the L-CRA treatment.

Secondary outcome [2]

A comparison of the residual central macula thickness changes as measured by Spectral Domain OCT from baseline to month 6, 12 and 24 in the combination treatment to previously reported data using Lucentis monotherapy.

Timepoint [2]

Baseline, Month 6, Month 12 and Month 24 after the L-CRA treatment.

Secondary outcome [3]

Monitor retinal and choroidal vasculature remodeling with Fluorescein angiography (FA) and Indocyanine green (ICG) angiography performed at Baseline, Month 12 and Month 24.

Timepoint [3]

Baseline, Month 12 and Month 24 after the L-CRA treatment.

Secondary outcome [4]

Monitor the nature and sequence of changes to radial peripapillary capillaries and the deep capillary networks using optical coherence tomography angiography (OCTA) at Baseline, Month 3, Month 6, Month 12 and Month 24.

Timepoint [4]

Baseline, Month 3, Month 6, Month 12 and Month 24 after the L-CRA treatment.

Eligibility

Key inclusion criteria

1. Foveal centre involved perfused macular oedema secondary to CRVO.
2. Mean central foveal thickness greater or equal to 250 microns on spectral domain OCT.
3. Adults greater or equal to 18 years.
4. Clear ocular media and adequate pupillary dilation.
5. IOP less or equal to 25mmHg.
6. Written informed consent.
7. No other significant pathology.
8. Willing, committed and able to return for all clinic visits and complete all study related procedures.
9. Patients who have had a previous CRVO that has spontaneously resolved will be enrolled provided there is no evidence of macular damage that would confuse visual acuity improvements.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Brisk afferent pupillary defect.
2. Evidence on examination of any diabetic retinopathy.
3. CVA or MI within 3 months prior to Baseline.
4. Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding.
5. Known sensitivity to study drug(s) or class of study drug(s).
6. Use of any other investigational agent in the last 30 days.
7. Any other ocular condition in the study eye that would prevent improvement in visual acuity. e.g. macular ischaemia, underlying macular degeneration, epi-retinal membrane.
8. Neovascularisation of the iris, disc or retina.
9. Aphakia or presence of anterior chamber lens in the study eye.
10. Significant media opacities such as cataract.
11. Previous pars plana vitrectomy.
12. History of retinal detachment or surgery for retinal detachment.
13. Any condition which would preclude a patient's ability to comply with the study requirements or to be available for the duration of the study.
14. Any active infection involving ocular adnexa including infectious conjunctivitis, keratitis, sclertitis, endophthalmitis as well as idiopathic or autoimmune associated uveitis in either eye.
15. Extra capsular extraction of cataract with phacoemulsification within three months preceding baseline, or a history of post-operative complications within the last 12 months preceding baseline in the study eye (uveitis, cyclitis etc.).
16. Contra indication to pupil dilation in either eye.
17. Anticoagulation with warfarin or other significant anticoagulation drugs.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

All participants will receive the combination treatment of L-CRA (laser bypass) and Lucentis injections.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Not applicable.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

100 patients will be recruited from the Investigator's clinic at Lions Eye Institute. All participants who present with a central retinal vein occlusion who meet the study inclusion/exclusion criteria will be asked if they wish to participate in the study. Because this is a phase IV study, no sample size calculations were used to determine this number. The number is based on the experience from the previous phase III study (L-CVBS study).

Data will be continuously analysed and response patterns compared with published results using monotherapy. Individual characteristics within the data set (e.g. duration, presenting BCVA, degree of ischaemia, concurrent medical conditions, smoking etc.) will be analysed for any evidence of modification of treatment effect.

Recruitment

Recruitment status

Active, not recruiting

Date of first participant enrolment

Anticipated

11/12/2015

Actual

11/12/2015

Date of last participant enrolment

Anticipated

31/07/2024

Actual

12/05/2023

Date of last data collection

Anticipated

30/05/2025

Actual

Sample size

Target

100

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Lions Eye Institute Day Surgery Centre - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Lions Eye Institute

Address [1]

Lions Eye Institute
2 Verdun St
Nedlands
Western Australia
6009

Country [1]

Australia

Primary sponsor type

Other

Name

Lions Eye Institute

Address

Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sir Charles Gairdner Hospital Human Research Ethics Committee

Ethics committee address [1]

Sir Charles Gairdner Hospital Human Research Ethics Committee, 2nd Floor, A Block, Sir Charles Gairdner Hospital, Hospital Ave, Nedlands, 6009, Westerm Australia.

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

27/10/2015

Approval date [1]

11/12/2015

Ethics approval number [1]

Summary

Brief summary

This is a monitoring study (phase IV) for participants with swelling in the back of the eye (macula oedema) that has been caused by a blockage to the main vein (retinal vein) draining the back of the eye (central retinal vein occlusion). The current treatment for this condition is a series of injections at monthly intervals of anti-VEGF antibodies (e.g. Lucentis or Avastin) into the back of the eye.  Whilst this treatment works well, there is often an ongoing need for the eye injections.  A laser treatment developed at the Lions Eye Institute, creates a channel from the retina (back of the eye) to the choroid (layer above the retina) for the blood to drain (laser bypass treatment). In the L-CVBS study participants who received the eye injections and laser bypass treatment require fewer eye injections longer term than participants who only receive the eye injections. Because the laser bypass and injection treatments work differently to address the swelling caused by the blockage, the combination of using both treatments tends to give patients a better visual outcome with fewer injections required.  Recruitment for the L-CVBS study has closed, and this new study is a follow on study, where all participants will receive eye injections and the laser bypass treatment. 

Participants with a macula oedema that is caused by a central retinal vein occlusion will be asked if they would like to participate in this study (consent obtained first). If eligible, all participants will receive the laser bypass treatment followed by the Lucentis injections. The standard loading dose of a monthly Lucentis injection for the first three months will be followed. Participants will be monitored monthly until Month 6. If there is evidence of macula oedema and/or vision loss, further monthly injections will be given until the participants condition stabilises. If after Month 6 visual and macula oedema stability is achieved, the visits can be extended to once every two months until Month 12. If stability is maintained from Month 12, then the visits can be extended to once every three months in the second year. But if visual acuity drops and/or if macular oedema is present, then the eye injections will resume and the visits will be monthly until stability is achieved. We hope to show that fewer injections are required to achieve visual and anatomic stability compared to studies where only Lucentis injections are used.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Ian McAllister

Address

Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia

Country

Australia

Phone

+61 8 9381 0870

Fax

+61 8 9381 0766

ian.mcallister@lei.org.au

Contact person for public queries

Name

Lynne Smithies

Address

Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia

Country

Australia

Phone

+61 8 9381 0790

Fax

+61 8 9381 0766

lynne.smithies@lei.org.au

Contact person for scientific queries

Name

Ian McAllister

Address

Lions Eye Institute
2 Verdun St
Nedlands
6009
Western Australia

Country

Australia

Phone

+61 8 9381 0870

Fax

+61 8 9381 0766

ian.mcallister@lei.org.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

All participant data is de-identified and not linked to the participant.
Ethics approval did not include the release of individual participant data.

What supporting documents are/will be available?

Doc. No.	Type	Email
6539	Study protocol	lynne.smithies@lei.org.au
6540	Informed consent form	lynne.smithies@lei.org.au
6541	Ethical approval	lynne.smithies@lei.org.au

Results publications and other study-related documents

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