The Most Effective Treatment Strategy for Diabetic Macular Edema.|
|- candidate number||14068|
|- NTR Number||NTR3742|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||7-dec-2012|
|- Secondary IDs||OZR-2011-17 / NL41998.078.12; Rotterdam Eye Hospital / CCMO|
|- Public Title||The Most Effective Treatment Strategy for Diabetic Macular Edema.|
|- Scientific Title||The Most Effective Treatment Strategy for Diabetic Macular Edema.|
|- ACRONYM||METS for DME|
|- hypothesis||Combined (repeated) laser photocoagulation prolongs time to failure compared to anti-VEGF monotherapy.|
|- Healt Condition(s) or Problem(s) studied||Diabetic macular edema|
|- Inclusion criteria||1. Age ≥ 18 years;|
2. Able to read and sign the written informed consent;
3. Diagnosis of DME, based on ETDRS criteria and confirmed by macular edema on optical coherence tomography (OCT, Heidelberg Spectralis), defined as CFT ≥ 340 micron (see Section 7.1 for argumentation for chosen cut-off value);
4. VA loss due to DME, with VA being between 45 and 85 letters as measured on ETDRS chart (Snellen decimal equivalent: 0.08 ¨C 0.63);
5. If both eyes are eligible, the eye with the highest CFT will be selected as the study eye. If both eyes have equal CFT, the eye with the most recent record of presence of DME will be selected as the study eye. The fellow eye will receive treatment according to the current standard of care at the investigator's discretion.
|- Exclusion criteria||1. Previous laser photocoagulation therapy within the last 6 months;|
2. Previous anti-VEGF therapy (Avastin, Lucentis, Eylea, or any investigational anti-VEGF drug) within the last 3 months;
3. Previous subtenon's or intravitreal triamcinolone injection within the last 6 months;
4. Steroid implants of any kind within the last 3 years;
5. Macular ischemia confirmed by fluorescein angiography (FA);
6. Vitreoretinal traction or epiretinal membranes with the potential of macular structural damage and function loss, confirmed by OCT;
7. Other eye conditions affecting VA prognosis, including pre-existent (deep) amblyopia;
8. Any ocular surgery/intervention within last three months before enrollment;
9. Any ocular surgery/intervention anticipated during the course of the study;
10. Ocular opacities hampering adequate imaging of the posterior pole;
11. Poor control of DM with glycated hemoglobin (HbA1c) of ≥ 86% in last 6 months;
12. Allergy to fluorescein or anti-VEGF, or any of its preservatives;
14. Non-Caucasian or Asian descent.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jan-2013|
|- planned closingdate||30-jun-2017|
|- Target number of participants||456|
|- Interventions||Group 1: Repeated SHAM;|
Group 2: LASER followed by SHAM;
Group 3: Repeated LASER.
All participants will receive four intravitreal anti-VEGF injections during the first period (week 0 till 19) and dependant on the study arm zero, one or two lasertreatments.
|- Primary outcome||Proportion of treatment failures at 72 weeks, with treatment failure defined at 24 weeks as < 50 micron decrease in CFT and no improvement in VA, i.e. 1 or more letters loss in VA, compared to baseline. After the 24 week visit failure of treatment is defined as > 50 micron increase in CFT, irrespective of VA, compared to week 24.|
|- Secondary outcome||1. Demographic data at baseline;|
2. ETDRS DRP grading;
3. Correlation of response rate to baseline VA, baseline CFT, baseline DRP grading, DM duration, DM control, prior DME therapy;
4. DME characteristics on OCT (diffuse or focal edema, size cystoids spaces);
5. Proportion of patients gaining 0-5, 5-10, 10-15 and >15 letters at 24 weeks and every subsequent visit until 72 weeks (compared to baseline);
6. Proportion of patients losing letters at 24 weeks compared to baseline;
7. Median time to treatment failure overall and for each treatment group;
8. Maximal VA during follow-up;
9. VA improvement during follow-up;
10. Maximal reduction in CFT;
11. Change in DRP grading;
12. Control of DM measured through HbA1c;
13. Safety parameters: proportion of (serious) adverse events, changes in intraocular pressure, progression of cataract and degree of DRP. In addition to safety data derived from this study, solicited safety data will be obtained from participants who continue observation in the cohort extension after withdrawal or treatment failure;
14. Change in the following questionnaires (from baseline through final follow-up visit):
|- Timepoints||Weeks 0, 1, 6, 12, 18, 19, 24, 30, 36, 48, 60, 72.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES|| T. Missotten|
|- CONTACT for SCIENTIFIC QUERIES|| T. Missotten|
|- Sponsor/Initiator ||The Rotterdam Eye Hospital|
(Source(s) of Monetary or Material Support)
|Combined Ophthalmic Research Rotterdam (CORR)|
|- Brief summary||Rationale: |
Diabetes mellitus is a worldwide epidemic with an anticipated prevalence of 4.4% in 2030. Diabetic macular edema (DME) often leads to severe visual acuity loss. It is expected that in 2025 there will be about 250.000 patients with DME in the Netherlands, with an annual incidence of 12.500 cases. Because of evident visual gain, current clinical treatment standards have switched from primary laser photocoagulation to (bi)monthly intravitreal anti-VEGF injections. It is conjectured that the outcome of photo¬coagulation therapy combined with intravitreal anti-VEGF injections is at least equivalent in visual outcome and, at the same time, helps to reduce the number of required intravitreal injections. With that, patient burden may become less and the growing demand on health care resources can be alleviated.
To demonstrate that combined (repeated) laser photocoagulation prolongs time to failure compared to anti-VEGF monotherapy.
Randomized, three-arms, double blind, comparative clinical trial.
Patients with DME.
Laser photocoagulation, intravitreal anti-VEGF injection.
Main study parameters/endpoints:
Proportion of failures to treatment at 72 weeks.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
Risks do not exceed those of regular DME treatment. Patients in combination groups may benefit from the additional treatment effect accomplished by laser photocoagulation. Visits required for this study coincide with the routine treatment/control schedule for DME, and study assessments are largely the same as in normal monitoring. Therefore, burden is considered to be negligible.
|- Main changes (audit trail)|
|- RECORD||7-dec-2012 - 8-jan-2013|
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