Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema (LOADEX)

Civil Hospices of Lyon

Status and phase

Active, not recruiting

Phase 2

Conditions

Diabetic Macular Edema

Treatments

Drug: Dexamethasone with 2 loading doses followed by PRN regimen.

Study type

Interventional

Funder types

Other

Identifiers

NCT04116398

69HCL19_0588

2024-514362-39-00 (EU Trial (CTIS) Number)

2019-003092-18 (EudraCT Number)

Details and patient eligibility

About

Nowadays, steroids and anti-VEGF are the first line treatment for diabetic macular edema. Ozurdex is the most frequently used steroid and has label for both first and second line treatment. Ozurdex treatment paradigm for patients with diabetic macular edema is to inject patient only in case of huge recurrence. The risk of this scheme is a progressive loss of vision due to photoreceptors loss. A more pro-active regimen, as it already exists for anti-VEGF treatment, would allow a better patient management. A new treatment paradigm consisting in a loading dose of 2 injections within 12 weeks, followed by a PRN (Pro Re Nata) regimen with strict retreatment criteria and minimal time limit of 12 weeks between two injections should result in a better visual acuity gain and a limited augmentation of the number of injections (which will remain lower than the number observed for anti-VEGF treatment).

The investigators have therefore chosen a pilot study to investigate the impact on efficacy and on the number of intravitreal injections (IVI) of such a scheme.

Enrollment

53 patients

Sex

All

Ages

18 to 40 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient > 40 years old
Patients with a significant DME : Macular thickening secondary to DME involving the center of the fovea, as measured by SD-OCT, with Central Subfield Thickness (CST) ≥ 285 μm measured on Spectralis/topcon or ≥ 275 μm, as measured on Cirrus, at screening and VA between 20/32 and 20/320 (between 23 and 78 letters ETDRS) using the ETDRS protocol at the initial testing distance of 4 meters at inclusion
Patient for which a dexamethasone implant is chosen
100% naive eyes (no history of steroids or anti-VEGF)
Pseudophakic for at least 3 months
HBA1c < 10%
Blood pressure < 160/95
Patient who give voluntary signed informed consent
Patient affiliated with the French universal health care system or similar
Patient able to participated in all visits and medical examinations during the study
If both eyes have to be treated, only one eye will be included : the eye with the lowest visual acuity at the baseline

Exclusion criteria

Aphatic eye without posterior lens capsule.
Study eye with implant anterior chamber of the eye or intraocular implant with iris fixated or transsclerally or ruptured posterior lens capsule.
Study eye with lens implant ARTISAN®
Ocular or periocular infection active or suspected in the study eye including most viral diseases of the cornea and conjunctiva, epithelial keratitis active Herpes simplex (dendritic keratitis), vaccinia, chickenpox, mycobacterial infections and mycoses
At inclusion, delay after cataract surgery < 3 months in the study eye
Delay after last session of panretineal Photocoagulation laser < 1 month in the study eye
Delay after last focal laser session of the posterior pole < 1 month in the study eye
Vitreomacular traction syndrome, associated ERM in the study eye
History of macular grid laser in the study eye
Focal laser only if the scars are located within 750 microns of the center (1/2 Papillary Diameter) in the study eye
Ischemic maculopathy (increase of more than 2 times the surface of the central avascular zone)
Proliferative diabetic Retinopathy in the study eye
Hypertension or Open Angle Glaucoma (OAG) treated by dual therapy eye drops or more
Patients with a systemic pathology that could interfere in the evolution of the Diabetic Macular Edema and treated by with immunosuppressive drugs, systemic steroids, anti-aldosterone or systemic anti-VEGF.
Patients with systemic treatment with a toxic effect on the lens, retina or optic nerve: deferoxime, chloroquine / hydroxychloroquine, tamoxifen, phenothiazines and ethambutol; in progress or within 6 months of inclusion
Hypersensitivity to the active substance or to any of the excipients and to anesthetic or hypotonizing eye drops
History of any pathology, metabolic disease, or any serious suspicion of disease at clinical or laboratory examination that contraindicates the use of the intra-retinal dexamethasone implant, could affect the interpretation of the results of the study or cause significant risks of complication for the subject
Infectious conjunctivitis and/or active or suspected appendix infection
Any eye condition or condition that the investigator believes may require intraocular surgery within 12 months
Eye contralateral that studied with visual acuity < 23 letters
Pregnant and breastfeeding woman
Female of reproductive age, sexually active, who does not want to commit to using adequate and highly effective contraception during the study and up to 6 months after the last administration of the study treatment:
- Combined hormonal contraception (containing estrogens and progestins) aimed at inhibiting ovulation (oral, intravaginal or transdermal);
- Hormonal contraception containing only a progestin intended to inhibit ovulation (oral, injectable or implantable);
- Intrauterine device (IUD);
- Intrauterine Hormone Release System (IUS);
- Ovariectomy with hysterectomy, bilateral tubal obstruction or total hysterectomy for at least 6 weeks before inclusion (for women included) or vasectomy for at least 6 months before inclusion (for partners of a patient included);
- Sexual abstinence. A woman will be considered to be of childbearing age from her first period and until the menopause, unless she is sterile or has had an oophorectomy type surgery with hysterectomy, bilateral tubal obstruction or hysterectomy total at least 6 weeks before inclusion. A post-menopausal state is defined as the absence of spontaneous menstruation (that is to say without any other medical treatment, in particular of the hormonal contraceptive type or hormone replacement therapy) for 12 months
Major patient protected under the terms of the law (Public Health Code)
Patient's ongoing participation in another interventional clinical trial (study eye and/or untreated eye)
Follow-up impossible for 24 months, the judgment of the investigator.