Cytokine and Visual Outcome Variations in Eyes Receiving Aflibercept (COVARIANT)
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|ClinicalTrials.gov Identifier: NCT03056079|
Recruitment Status : Recruiting
First Posted : February 17, 2017
Last Update Posted : September 19, 2019
Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic macular edema (DME).
Methods: A prospective, single-centre study will be performed containing 3 sub-studies according to each study population: nAMD, macular edema secondary to RVO and DME. Inclusion criteria are: patients followed at St. Michael's Hospital with the diagnosis of nAMD, macular edema secondary to RVO or DME. Patients will be excluded if visual acuity is worse than counting fingers, with macular pathologies causing any structural changes to the retina, have received anti-VEGF injections or photocoagulation therapy 6 months prior to study, intraocular surgery 3 months prior to study, any history of vitreoretinal surgery or ocular inflammation in the study eye, use of systemic or topical anti-inflammatory or steroids, patients on dialysis for renal failure, allergy to the study drug or fluorescein, <18 years old, women who are pregnant. All patients will be treated with aflibercept intravitreal injections on a variable dosing regimen: Patients with DME will be examined monthly and receive mandatory injection for the first three months (baseline, weeks 4 and 8). Afterwards, they will continue to be seen monthly and the need for new injections will be decided upon the clinical findings at each visit. An anterior chamber (AC) tap will be done if an injection is required at the visit. Patients with nAMD and RVO will be examined monthly and receive mandatory injection for the first three months. From weeks 12 until 72 (month 18), the visits will be scheduled at increasing 2-weeks intervals based on the stability of the ocular condition and response to treatment. At each visit, an injection and AC tap will be performed. The maximum interval in between injections is 12 weeks. If the disease becomes unstable, the interval in between injections is shortened and, once it stabilizes, the treatment frequency is extended again. In all patients, baseline aqueous humour specimens will be obtained prior to the first aflibercept intravitreal injection and follow-up samples will be taken immediately prior to subsequent injections based on the treatment regimens for cytokine analysis in the end of the follow-up.
|Condition or disease||Intervention/treatment||Phase|
|Age Related Macular Degeneration Diabetic Macular Edema Retinal Vein Occlusion Macular Edema||Drug: Intravitreal aflibercept||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||168 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||This study will contain 3 populations of patients which will all receive aflibercept injections: one with neovascular age-related macular degeneration, other with diabetic macular edema and a third with macular edema secondary to retinal vein occlusion.|
|Masking:||None (Open Label)|
|Official Title:||Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Aflibercept Treatment: The COVARIANT Study|
|Actual Study Start Date :||February 28, 2017|
|Estimated Primary Completion Date :||February 28, 2020|
|Estimated Study Completion Date :||February 28, 2020|
Patients presenting to St. Michael's Hospital retina clinic with neovascular AMD, macular edema secondary to retinal vein occlusion and diabetic macular edema treated with intravitreal aflibercept in a variable dosing regimen.
Drug: Intravitreal aflibercept
Patients will receive intravitreal aflibercept on a variable dosing regimen and have aqueous humor sample obtained for cytokine analysis at every visit when an intravitreal injection is done.
Other Name: Eylea
- Association between cytokine levels and optimal treatment interval [ Time Frame: 18 months ]Optimal interval between injections based on aqueous cytokine levels
- Individualized aqueous cytokine curves relationship with treatment response [ Time Frame: 18 months ]Aqueous cytokine curves for each patient based on the relationship between cytokine levels and treatment response
- Cytokine threshold level with visual and anatomic outcomes [ Time Frame: 18 months ]Cytokine threshold level below which visual and anatomic outcomes are greatest
- Snellen BCVA change [ Time Frame: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. ]To assess Snellen Best Corrected Visual Acuity (BCVA) change at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
- ETDRS visual acuity change [ Time Frame: month 2, at the visits closest to injection of months 6, 12 and 18. ]Visual acuity (ETDRS) change at month 2 (at the third injection), at the visits closest to injection of months 6, 12 and 18.
- Optical coherence tomography change [ Time Frame: months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period. ]Anatomic OCT change (Macular Volume, Central Macular Thickness) at months 1 and 2, and at the visits scheduled for each injection throughout an 18 months period.
- Average number of injections needed [ Time Frame: 18 months ]Average number of injections needed in a variable dosing regimen protocol over an 18 months period.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03056079
|Contact: Rajeev Muniemail@example.com|
|Department of Ophthalmology, St Michael's Hospital||Recruiting|
|Toronto, Ontario, Canada, M5C 2T2|
|Principal Investigator: Rajeev H Muni, FRCSC|
|Sunnybrook Health Sciences Centre||Recruiting|
|Contact: Peter Kertes|
|Principal Investigator:||Rajeev Muni||St. Michael's Hospital, Toronto|