COVERT: Cytokine and Visual Outcome Variations in Eyes Receiving Ranibizumab

Sponsor

Unity Health Toronto (Other)

Overall Status

Recruiting

CT.gov ID

NCT03056092

Collaborator

(none)

168

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal ranibizumab 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 ranibizumab 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 ranibizumab 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 Macular Edema Retinal Vein Occlusion	Drug: Intravitreal ranibizumab	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

168 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This study will include patients with 3 different diseases who will receive the same treatment (ranibizumab injections) but that will be independently analyzed. One population will be composed of patients with neovascular age related macular degeneration, the other of diabetic macular edema and the third of patients with macular edema secondary to retinal vein occlusion.This study will include patients with 3 different diseases who will receive the same treatment (ranibizumab injections) but that will be independently analyzed. One population will be composed of patients with neovascular age related macular degeneration, the other of diabetic macular edema and the third of patients with macular edema secondary to retinal vein occlusion.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Cytokine and Visual Outcome Variations in Eyes Receiving a Variable Dosing Ranibizumab Treatment: The COVERT Study

Actual Study Start Date :

Feb 28, 2017

Anticipated Primary Completion Date :

Feb 28, 2024

Anticipated Study Completion Date :

Feb 28, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: AMD/RVO/DME Patients presenting to St. Michael's Hospital retina clinic with neovascular age related macular degeneration, macular edema secondary to RVO and diabetic macular edema treated with intravitreal ranibizumab in a variable dosing regimen.	Drug: Intravitreal ranibizumab Patients will be treated with intravitreal ranibizumab and have their aqueous humor obtained for cytokine analysis at every visit that an intravitreal injection is done

Arm

Intervention/Treatment

Other: AMD/RVO/DME

Patients presenting to St. Michael's Hospital retina clinic with neovascular age related macular degeneration, macular edema secondary to RVO and diabetic macular edema treated with intravitreal ranibizumab in a variable dosing regimen.

Drug: Intravitreal ranibizumab

Patients will be treated with intravitreal ranibizumab and have their aqueous humor obtained for cytokine analysis at every visit that an intravitreal injection is done

Outcome Measures

Primary Outcome Measures

Association between aqueous cytokine levels and optimal treatment interval [18 months]
Optimal treatment intervals based on aqueous cytokine levels

Secondary Outcome Measures

Individualized relationships between aqueous cytokines and treatment response [18 months]
Aqueous cytokine curves for each patient over based on the relationship between cytokine levels and treatment response
Relationship between cytokine threshold level and visual/anatomic outcomes [18 months]
Cytokine threshold level below which visual and anatomic outcomes are greatest
Snellen visual acuity change [months 1, 2 and at every visit scheduled for each injection throughout 18 months period]
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 [month 2, 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 (OCT) change [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 [18 months]
Average number of injections needed in a variable dosing regimen protocol over an 18 months period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 for patients with AMD
Previous photocoagulation therapy within 6 months in the study eye or anticipated need for during the course of the study for 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 for 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