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Trial registered on ANZCTR


Registration number
ACTRN12610001004055
Ethics application status
Approved
Date submitted
5/11/2009
Date registered
17/11/2010
Date last updated
7/01/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of Methotrexate injections into the eye for inflammatory diseases of the eye.
Scientific title
Prospective, Phase II , non-randomised interventional case series of the safety and efficacy of the use of intra-vitreal methotrexate in the treatment of macular oedema secondary to uveitis
Secondary ID [1] 253110 0
HREC 09/907H
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Visual loss due to macular oedema secondary to uveitis 252128 0
Condition category
Condition code
Eye 252336 252336 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single Intraviteal methotrexate injection 400mcg/0.1ml; repeated monthly as required
Intervention code [1] 241507 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 253208 0
Best corrected Snellan Visual Acuity at baseline (pre treatment) and at 3 monthly timepoints over a maximum of 12 months
Timepoint [1] 253208 0
Every 6 weeks post injection for 12 months
Secondary outcome [1] 262139 0
Central Macular thickness as measured on OCT at baseline and at 3 monthly intervals over 12 months
Timepoint [1] 262139 0
Every 6 weeks post injection for 12 months
Secondary outcome [2] 262140 0
Uveitic activity as per the Standardised Uveitis Nomenclature (SUN) criteria
Timepoint [2] 262140 0
Every 6 weeks post injection for 12 months

Eligibility
Key inclusion criteria
(i) Over 18 years of age
(ii) Active non-infectious intermediate, posterior or panuveitis, defined as vitreal cell, vitreal haze, inflammatory debris and/or active chorioretinal lesions of a degree for which systemic or intravitreal corticosteroid treatment is indicated that has either been unresponsive to standard treatment (including intravitreal triamcinolone) or where further local steroid treatment is relatively contraindicated (e.g. pre-existing glaucoma or steroid responder), OR
(iii) Uveitic cystoid macular oedema in one or both eyes that has either been unresponsive to standard treatment (including intravitreal triamcinolone) or where further local steroid treatment is relatively contraindicated (e.g. pre-existing glaucoma or steroid responder)
(iv) Best corrected visual acuity in the affected eye(s) = 6/12 or worse
(v) Subjects must have signed the informed consent form
Minimum age
18 Years
Maximum age
90 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Loss of vision due to other causes (e.g. myopic macular degeneration)
(ii) Significant macular ischaemia (as determined on Fundus Fluorescein angiography)
(iii) Known allergies to methotrexate
(iv) Active ocular infection (eg. Conjunctivitis, keratitis)
(v) Intercurrent severe disease such as septicaemia
(vi) History of other systemic disease(s) that, in the opinion of the investigator, may render the subject at a high risk for treatment complications
(vii) Any condition which would affect follow-up or photographic documentation (e.g. geographical, psycho-social, media opacities)
(viii) Unwillingness or inability to give informed consent
(ix) Under age 18
(x) Pregnant or lactating women
(xi) Premenopausal women of child bearing potential not using adequate contraception. Adequate contraception includes the use of one or more of the following: surgical sterilisation (tubal ligation), hormonal sterilisation (implant, patch or oral), and double barrier methods (any double combination of: an intrauterine device (IUD), condom with spermicidal gel, diaphragm, sponge, cervical cap). Reliable contraception must be maintained throughout the study and for 30 days after methotrexate discontinuation.

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)
Participants would be recruited from subjects known to have active non-infectious intermediate, posterior or panuveitis; or uveitic macular oedema involving the fovea in one or both eyes. These patients will be outpatients recruited from the Ocular Immunology Clinic of the Royal Victorian Eye and Ear Hospital.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 243978 0
Hospital
Name [1] 243978 0
Royal Victorian Eye and Ear Hospital
Address [1] 243978 0
32 Gisborne Street
East Melbourne,
Victoria 3002
Country [1] 243978 0
Australia
Primary sponsor type
Hospital
Name
Royal Victorian Eye and Ear Hospital
Address
32 Gisborne Street
East Melbourne,
Victoria 3002
Country
Australia
Secondary sponsor category [1] 251331 0
University
Name [1] 251331 0
Centre for Eye Research, University of Melbourne
Address [1] 251331 0
32 Gisborne Street
East Melbourne,
Victoria 3002
Country [1] 251331 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 244088 0
Royal Victorian Eye and Ear Hospital
Ethics committee address [1] 244088 0
32 Gisborne Street
East Melbourne,
Victoria 3002
Ethics committee country [1] 244088 0
Australia
Date submitted for ethics approval [1] 244088 0
Approval date [1] 244088 0
02/09/2009
Ethics approval number [1] 244088 0
09/907H

Summary
Brief summary
Uveitis is a term that refers to inflammatory diseases of the eye. Uveitis accounts for about 10% of the legal blindness in developed countries such as Australia and the United States and is roughly comparable to diabetes in terms of years of visual loss.

The most severe forms of uveitis have the highest risk of vision loss. One of the common causes of vision loss in uveitis is swelling of the central retina, or “macular oedema”. This is due to the abnormal leakage of fluid from blood vessels within the retina as a result of uncontrolled inflammation.

Standard treatments for severe uveitis and associated complications like macular oedema include systemic medication or injections of long acting steroid into, or around the eye. Systemic treatments include steroid tablets or low doses of drugs that are also used in chemotherapy like cyclophosphamide or cyclosporine. These systemic treatments have significant associated side effects and therefore are not ideal, particularly in people who only have uveitis in one eye.

Injections of a long acting steroid (triamcinolone) directly into the eye (“intra-vitreally”) is another established treatment modality for some types of uveitis and blinding complications like uveitic macular oedema, particularly in those with uveitis in only one eye. However, there are known side effects of this treatment such as cataract, glaucoma, infection (endophthalmitis) and retinal detatchment. Of these, cataract and glaucoma are by far the most common and, unlike the other complications, are the direct result of the effect of triamcinolone on the eye, rather than being a complication of the injection procedure.

Although the visual loss from cataract may be reversed with cataract surgery, visual loss from glaucoma can only be halted with available treatments and not reversed. Therefore patients who have glaucoma, or are known to develop raised intraocular pressures in response to steroid treatment (such as triamcinolone), are not offered this treatment, thereby limiting the available options for the management of their uveitis and/or uveitic macular oedema.

Methotrexate is a drug that has been used in chemotherapy but also in low doses to control inflammatory diseases like rheumatoid arthritis in both adults and children. More recently, it has also been used as an injection intravitreally to treat both ocular lymphoma as well as uveitis and uveitic macular oedema.

Preliminary studies using methotrexate intravitreally as treatment for severe forms of uveitis and associated sight threatening complications like macular oedema appear promising, without the side effects known to be associated with steroid treatment such as cataract and glaucoma.

We therefore have 2 specific aims:
Aim 1: To prospectively evaluate the efficacy of intavitreal methotrexate in the treatment of active intermediate, posterior or panuveitis
Aim 2: To prospectively evaluate the efficacy of intravitreal methotrexate in the treatment of uveitic macular oedema
Trial website
N/A
Trial related presentations / publications
Results presented at the Melbourne Ophthalmic Alumni Meeting, Melbourne, Victoria, June 2011
Public notes

Contacts
Principal investigator
Name 30466 0
Dr Dr Lyndell Lim
Address 30466 0
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Locked Bag 8, East Melbourne, Victoria, 8002
Country 30466 0
Australia
Phone 30466 0
+61399298759
Fax 30466 0
+61399298030
Email 30466 0
limllp@unimelb.edu.au
Contact person for public queries
Name 13713 0
Dr Lyndell Lim
Address 13713 0
Centre for Eye Research Australia,
Royal Victorian Eye and Ear Hospital,
Locked Bag 8,
East Melbourne,
Victoria, 8002
Country 13713 0
Australia
Phone 13713 0
+613 9929 8759
Fax 13713 0
+613 9929 8030
Email 13713 0
limllp@unimelb.edu.au
Contact person for scientific queries
Name 4641 0
Dr Lyndell Lim
Address 4641 0
Centre for Eye Research Australia,
Royal Victorian Eye and Ear Hospital,
Locked Bag 8,
East Melbourne,
Victoria, 8002
Country 4641 0
Australia
Phone 4641 0
+613 9929 8759
Fax 4641 0
+613 9929 8030
Email 4641 0
limllp@unimelb.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary