TRIOZ: Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema

Sponsor

Nantes University Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02556424

Collaborator

(none)

114

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Corticosteroids, whether injected peri- or intra-ocularly, remain indispensable tools of the therapeutic arsenal in treating inflammatory macular edema. However, a few years ago, only triamcinolone acetonide was available to ophthalmologists. This molecule, developed initially for rheumatological or dermatological use, has been increasingly deployed in ophthalmology, while still off-label.

In 2011, the delivery system of dexamethasone from biodegradable and injectable implant into the vitreous cavity obtained the label for inflammatory macular edema. This protocol is therefore designed to compare the efficacy and safety of peri- and intra-ocular injections of corticosteroids in the treatment of inflammatory macular edema.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Macular Edema	Drug: Dexamethasone Drug: Triamcinolone	Phase 3

Detailed Description

This research compares the implantation techniques of corticosteroids in the eye, with two groups of equal size being followed. This is a multi-center, controlled study, with the reference drug being the intravitreal implant of 700μg of dexamethasone (Ozurdex®) compared to subconjunctival injection of triamcinolone (Kénacort retard®). This is an open, prospective, randomized study. It is not possible, for technical reasons, to inject blind two products with different injection routes and that are visible to the investigator during control examinations (sub-conjunctival crystals and intravitreal implant). However, the assessment of visual acuity and central macular thickness will be performed by an uninformed ophthalmologist.

Study Design

Study Type:

Interventional

Actual Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Tolerance Comparison Between Subconjunctival Injection of Triamcinolone and Intravitreal Implant of Dexamethasone for the Treatment of Inflammatory Macular Edema

Actual Study Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2020

Anticipated Study Completion Date :

Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Reference Drug Intravitreal implant of 700μg of dexamethasone (Ozurdex®)	Drug: Dexamethasone Intravitreal implant at D0 Other Names: Ozurdex®
Experimental: Tested Drug Subconjunctival injection of 16 mg triamcinolone (Kénacort Retard®)	Drug: Triamcinolone Subconjunctival injection at 4 mm from the limbus at 6 o'clock Other Names: Kénacort retard®

Arm

Intervention/Treatment

Active Comparator: Reference Drug

Intravitreal implant of 700μg of dexamethasone (Ozurdex®)

Drug: Dexamethasone

Intravitreal implant at D0

Other Names:

Ozurdex®

Experimental: Tested Drug

Subconjunctival injection of 16 mg triamcinolone (Kénacort Retard®)

Drug: Triamcinolone

Subconjunctival injection at 4 mm from the limbus at 6 o'clock

Other Names:

Kénacort retard®

Outcome Measures

Primary Outcome Measures

Evaluation of the effectiveness of a subconjunctival injection of triamcinolone on reducing the central macular thickness versus an intravitreal implant of dexamethasone between patient selection and 2 months after treatment [At 2 months after treatment]
Difference of the central macular thickness in the treated eye, measured by Optical Coherence Tomography (OCT) spectral domain, for each patient between patient selection and 2 months after treatment

Secondary Outcome Measures

Evaluation of the experience of the injection by a questionnaire (tolerable, unpleasant and very unpleasant) and by EVA (0 cm = no pain to 10 cm = extreme pain) [At day 0 (= the day of the treatment)]
Scale of "patient experience" the day of the injection (tolerable, unpleasant, very unpleasant) and visual analogue scale (VAS)
Evaluation of the effectiveness of the studied injection at each visit regarding gain in visual acuity (ETDRS) [Up to 6 months]
Visual acuity (ETDRS)
Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the anterior flare [Up to 6 months]
Anterior flare ("Lampe A Fente" and Laser Flare Meter, if available)
Evaluation of the effectiveness of the studied injection at each visit regarding reduction of the vitreous haze [Up to 6 months]
Vitreous flare
Evaluation of the effectiveness of the studied injection at each visit regarding central macular thickness measured by OCT, allowing the evaluation of the duration of action of the treatment [Up to 6 months]
Central macular thickness of the eye treated for determining the duration of action
Evaluation of the effectiveness of the studied injection at each visit regarding local and general tolerance, by collecting all Adverse Events (AEs) / Serious Adverse Events (SAEs) [Up to 6 months]
Evaluation of tolerance by collecting all AEs / SAEs of randomized patients, such as intra-ocular hypertension, cataracts, endophthalmitis, poor glycemic and/or blood pressure control
Evaluation of the effectiveness of the studied injection at each visit regarding patients' quality of life [Up to 6 months]
Patients' quality of life questionnaire (EQ-5D)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient, male or female (under effective contraception if premenopausal) over 18 years old
Patient affiliated with a social security plan
Patient able to understand and follow the instructions of the study
Patient having signed an informed consent
Patient having a central macular thickness greater than 320μm (Spectral Domain, 270µm Time Domain)
Patient with an inflammatory macular edema, unilateral or bilateral (in the case of a bilateral inflammatory macular edema, the eye most affected will be treated)

Exclusion Criteria:

Patient with an infectious uveitis
Patient with uncontrolled active infection
Patient receiving an unbalanced general anti-inflammatory and/or immunosuppressive and/or immunomodulatory therapy (recent modification <1 month)
Patient having a history of glaucoma and/or ocular hypertension in the eye studied (intraocular pressure (IOP) > 25 mmHg without antiglaucoma medication or > 21 mmHg with antiglaucoma combination therapy) and/or cortisone-causing-hypertension not controlled by an antiglaucoma dual therapy
Patient with uncontrolled diabetes (HbA1c> 8%) or unbalanced hypertension (Systolic Blood Pressure > 160 mmHg and/or Diastolic Blood Pressure > 100mmHg)
Edematous diabetic maculopathy
Patient who had received triamcinolone (subconjunctivally or sub-tenon) 3 months before randomization, or 700μg dexamethasone intravitreally 6 months before randomization
Suspected or active ocular or periocular infection, including most viral diseases of the cornea and conjunctiva, such as active epithelial keratitis with herpes simplex (dendritic keratitis), vaccinia, varicella, mycobacterial infections and mycoses
History of ocular herpes infection or central serous chorioretinopathy
Aphakic eye with rupture of the posterior lens capsule
Eye with implant in the anterior chamber, iris- or transscleral-fixated intraocular implant and rupture of the posterior lens capsule
Uncontrolled systemic inflammatory disease.
Known hypersensitivity to the active substance or to one of the excipients of Ozurdex®, Kenacort® or injectable fluorescein
Pregnant woman or likely to become pregnant or nursing
Patient participating in another clinical trial
Adult under a legal protection regime (guardianship, trusteeship, "sauvegarde de justice")

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Angers	Angers	France
2	CHU de Bordeaux	Bordeaux	France	33076
3	CHU de Brest	Brest	France	29609
4	CHU de Dijon	Dijon	France	21079
5	CHU de Grenoble	La Tronche	France	38700
6	Hôpital Bicêtre (AP-HP)	Le Kremlin-Bicêtre	France	94270
7	CHRU de Lille	Lille	France	59037
8	Hopices Civils de Lyon	Lyon	France	69004
9	CHU de Montpellier	Montpellier	France	34295
10	CHU de Nantes	Nantes	France	44093
11	CHU de Nice	Nice	France	06000
12	Hôpital La Pitié-Salpêtrière (AP-HP)	Paris	France	75013
13	Fondation Ophtalmologique Adolphe de Rothschild	Paris	France	75019
14	Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts	Paris	France	75571
15	CHU de Tours	Tours	France	37044
16	CHU de Nancy	Vandoeuvre-les-Nancy	France	54500