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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
Sponsor:
Information provided by (Responsible Party):
St. Michael's Hospital, Toronto

Tracking Information
First Submitted Date  ICMJE February 1, 2017
First Posted Date  ICMJE February 17, 2017
Last Update Posted Date September 19, 2019
Actual Study Start Date  ICMJE February 28, 2017
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
Association between cytokine levels and optimal treatment interval [ Time Frame: 18 months ]
Optimal interval between injections based on aqueous cytokine levels
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cytokine and Visual Outcome Variations in Eyes Receiving Aflibercept
Official Title  ICMJE Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Aflibercept Treatment: The COVARIANT Study
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
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)
Primary Purpose: Treatment
Condition  ICMJE
  • Age Related Macular Degeneration
  • Diabetic Macular Edema
  • Retinal Vein Occlusion
  • Macular Edema
Intervention  ICMJE 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
Study Arms  ICMJE AMD/RVO/DME
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.
Intervention: Drug: Intravitreal aflibercept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2017)
168
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2020
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of active choroidal neovascularization secondary to AMD in the study eye
  • Diagnosis of macular edema secondary to RVO: central macular thickness >310μm due to intraretinal or subretinal edema in the study eye as measured on OCT
  • Diagnosis of DME with central macular thickness >310μm in the study eye as measured on OCT in patients with diabetes mellitus types 1 or 2

Exclusion Criteria:

  • • Previous intravitreal drug injections in either eye within 6 months prior to study enrollment

    • Visual acuity worse than counting fingers
    • Patients with other macular pathologies causing structural changes to the retina
    • Patients with large submacular hemorrhages or extensive fibrosis occupying the majority (>50%) of the lesion
    • Intraocular surgery in the study eye 3 months prior to study enrollment
    • Previous vitreoretinal surgery in the study eye
    • Previous photodynamic or macular photocoagulation therapy within the past 6 months in the study eye in patients with AMD
    • Previous photocoagulation therapy within 6 months in the study eye or anticipated need for during the course of the study in patients with RVO
    • Presence of active proliferative diabetic retinopathy or patients who have had pan-retinal photocoagulation within 6 months or patients where the need to pan-retinal photocoagulation is anticipated during the course of the study in patients with DME
    • History of intraocular inflammation in the study eye
    • Patients on systemic or topical anti-inflammatory or steroids medications
    • Patients receiving dialysis for renal failure
    • Known allergy to the study drug or fluorescein
    • Patients who are pregnant
    • Unwilling or unable to follow or comply with all study related procedures or to sign consent form
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rajeev Muni 416-867-7411 rajeev.muni@utoronto.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03056079
Other Study ID Numbers  ICMJE COVARIANT
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party St. Michael's Hospital, Toronto
Study Sponsor  ICMJE St. Michael's Hospital, Toronto
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rajeev Muni St. Michael's Hospital, Toronto
PRS Account St. Michael's Hospital, Toronto
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP