Clinical trial NCT04116398: Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema (LOADEX)
Official title: Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Diabetic Macular Edema
Keywords: dexamethasone,
loading dose,
diabetic macular edema
pseudophakic
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-10-04
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum BCVA (Best Corrected Visual Acuity) change (best improvement) from baseline (during one year of treatment)
timeFrame: 52 weeks
Secondary outcomes:
measure: The time required to obtain the best BCVA
timeFrame: 52 weeks
measure: The number of injections required to obtain the best BCVA
timeFrame: 52 weeks
measure: the maximum best corrected visual acuity (BCVA) change (best improvement) measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale
timeFrame: between the baseline and 1,5 years and between the baseline and 2 years
measure: values of Visual Acuity (VA) at each visit
timeFrame: all visits during 2 years
measure: Area under the curve (AUC) of VA
timeFrame: between the baseline and 52 weeks and between the baseline and 2 years
measure: Description of Visual acuity (VA)
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: Number of IVI
timeFrame: 1 year
measure: Number of IVI
timeFrame: 2 years
measure: OCT parameters: Central Subfield Mean Thickness (CSMT)
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters: Central Fovea Thickness
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of interruptions of the ellipsoid line
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of continuous external limiting membrane
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the which obtained the BCVA
measure: OCT parameters : presence of disorganization of the internal retinal layers
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of intraretinal cysts
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of vitreomacular traction
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtain the BCVA
measure: OCT parameters : presence of epiretinal membrane
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of macular exudates
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : persistance of foveolar depression
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
measure: OCT parameters : presence of intraretinal fluid
timeFrame: at each visit
measure: Proportion of patients with macular edema resolution
timeFrame: at 1 year
measure: Proportion of patients with macular edema resolution
timeFrame: at 2 years
measure: Retinopathy parameters : presence of intraretinal or subretinal macular hemorrhage
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Retinopathy parameters: presence of microaneurisms
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Retinopathy parameters : presence of macular exudates
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Severity evolution (improvement, no change, worsening) of diabetic retinopathy graded by 2 evaluators on stereoscopic 7-field color fundus photographs
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Quantitative OCT-angiography analysis : the size of non-perfusion zones
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Quantitative OCT-angiography analysis : the size of central avascular zones
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Qualitative OCT-angiography analysis : presence of macular ischemia
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Qualitative OCT-angiography analysis : Evolution of macular ischemia compared to the baseline
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Qualitative OCT-angiography analysis : presence of preretineal neovessels
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Qualitative OCT-angiography analysis : evolution of preretineal neovessels compared to the baseline
timeFrame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
measure: Biomicroscopy: the number and the percentage by categories of the condition of the implant
timeFrame: all visits during 2 years
measure: Biomicroscopy: presence of the state of the posterior capsule
timeFrame: all visits during 2 years
measure: Variation of the intraocular pressure
timeFrame: all visits during 2 years
measure: proportion of patients using hypotonic eye treatment
timeFrame: all visits during 2 years
measure: Number of adverse events
timeFrame: all visits during 2 years
measure: Level of discomfort felt by the patient
timeFrame: all visits during 1 year
Other outcomes:
Locations:
city: Bobigny
country: France
facility: APHP - Hôpital Avicenne
city: Bordeaux
country: France
facility: CHU Bordeaux - Hôpital Pellegrin
city: Bordeaux
country: France
facility: Centre Rétine Gallien
city: Créteil
country: France
facility: Hôpital Intercommunal de Créteil
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHRU Lille - Hôpital Huriez
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hospices Civils de Lyon - Hopital de la Croix Rousse
city: Marseille
country: France
facility: Centre Monticelli Paradis d'ophtalmologie
city: Marseille
country: France
facility: APHM - Hôpital Nord
city: Marseille
country: France
facility: Clinique Juge
city: Paris
country: France
facility: APHP - Hôpital Lariboisière
city: Paris
country: France
facility: Centre Hospitalier National d'Ophtalmologie des XV XX
city: Poitiers
country: France
facility: CHU de Poitiers - La miletrie
city: Rouen
country: France
facility: Clinique Mathilde
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital Pierre Paul Riquet
Study officials:
References: