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

April 16, 2024 updated by: Hospices Civils de Lyon

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Avignon, France, 84000
        • Recruiting
        • CH Henri Duffaut
        • Contact:
        • Principal Investigator:
          • Caroline MARC
      • Bobigny, France, 93000
        • Recruiting
        • APHP - Hôpital Avicenne
        • Contact:
        • Principal Investigator:
          • Audrey GIOCANTI-AUREGAN
      • Bordeaux, France, 33000
      • Bordeaux, France
        • Not yet recruiting
        • Centre Rétine Gallien
        • Contact:
          • Laurence ROSIER
        • Principal Investigator:
          • Laurence ROSIER
      • Caen, France
        • Not yet recruiting
        • Polyclinique du Parc - Caen & Cabinet Ophtalmologie Dr Rysanek
        • Contact:
          • Boris RYSANEK
        • Principal Investigator:
          • Boris RYSANEK
      • Clermont-Ferrand, France, 63003
      • Créteil, France, 94010
        • Recruiting
        • Hôpital Intercommunal de Créteil
        • Contact:
        • Principal Investigator:
          • Eric SOUIED
      • Dijon, France, 21079
      • Eaubonne, France
        • Not yet recruiting
        • Centre Hospitalier Simone Veil Eaubonne SITE D'EAUBONNE
        • Contact:
          • Pierre-Antoine FORTE
        • Principal Investigator:
          • PIerre-Antoine FORTE
      • Ecully, France
        • Not yet recruiting
        • Clinique du Val d'Ouest - Centre Ophtalmologique Pôle Vision
        • Contact:
          • CORNUT Pierre Loic
        • Principal Investigator:
          • CORNUT Pierre Loic
        • Principal Investigator:
          • DEBATS Flore
        • Principal Investigator:
          • NGUYEN Anh-Minh
      • Lille, France, 59037
        • Recruiting
        • CHRU Lille - Hôpital Huriez
        • Contact:
        • Principal Investigator:
          • Pierre LABALETTE
      • Lyon, France, 69004
      • Lyon, France, 69003
        • Not yet recruiting
        • Hôpital Edouard Herriot
        • Principal Investigator:
          • Corinne DOT
        • Contact:
      • Marseille, France, 13008
        • Recruiting
        • Centre Monticelli Paradis d'ophtalmologie
        • Contact:
        • Principal Investigator:
          • Frédéric MATONTI
      • Marseille, France, 13015
      • Nice, France, 06000
        • Recruiting
        • CHU Nice - Hôpital Pasteur 2
        • Contact:
        • Principal Investigator:
          • Stéphanie BAILLIF
      • Paris, France, 75010
        • Recruiting
        • APHP - Hôpital Lariboisière
        • Contact:
        • Principal Investigator:
          • Aude COUTURIER
      • Paris, France, 75012
        • Recruiting
        • Centre Hospitalier National d'Ophtalmologie des XV XX
        • Contact:
          • R ADAM
        • Principal Investigator:
          • R ADAM
      • Paris, France, 75013
        • Recruiting
        • APHP - Hôpital La Pitié Salpetrière
        • Contact:
        • Principal Investigator:
          • Sarah Touhami
      • Paris, France
        • Not yet recruiting
        • APHP - Hôpital Cochin
        • Contact:
          • Francine BEHAR-COHEN
        • Principal Investigator:
          • Francine BEHAR-COHEN
      • Poitiers, France, 86000
      • Reims, France, 51092
        • Recruiting
        • CHU Reims - Hôpital Robert Debré
        • Principal Investigator:
          • Carl ARNDT
        • Contact:
      • Rouen, France
        • Not yet recruiting
        • Clinique Mathilde
        • Contact:
        • Principal Investigator:
          • Joel UZZAN
      • Toulouse, France, 31059
        • Recruiting
        • CHU Toulouse - Hôpital Pierre Paul Riquet
        • Contact:
        • Principal Investigator:
          • Fanny VARENNE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

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 6 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ozurdex®, 700µg dexamethasone intravitreal injection
Intravitreal injection of dexamethasone (Ozurdex®)
Drug: Dexamethasone with 2 loading doses followed by PRN regimen.
  • Loading dose with 2 systematic intravitreal injections (IVI) of ozurdex at the baseline and 12 weeks.Followed by a PRN regimen with strict retreatment criteria (already used and published in the Prediamex study, Bellocq,Kodjikian et al Ophthalmology Retina 2017)
  • Retreatment criteria: Reduction in VA ≥ 5 ETDRS Letters; and/or CSMT ≥ 275 microns by OCT-Cirrus® or ≥ 285 microns by OCT Spectralis®/Topcon; and/or increase of CSMT > 50 microns; and/or onset of recurrent retinal cysts; and/or residual edema considered by the practitioner to be clinically significant.
  • Minimal time limit between two IVI : 12 weeks
  • Visits: monthly during 1 year (to check efficacy and safety) and then for the 2nd-year only at Month18 (M18) and Month 24 (M24)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum BCVA (Best Corrected Visual Acuity) change (best improvement) from baseline (during one year of treatment)
Time Frame: 52 weeks
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS scale at an initial distance of 4 meters.
52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The time required to obtain the best BCVA
Time Frame: 52 weeks
average, standard deviation, median, minimum and maximum
52 weeks
The number of injections required to obtain the best BCVA
Time Frame: 52 weeks
average, standard deviation, median, minimum and maximum
52 weeks
the maximum best corrected visual acuity (BCVA) change (best improvement) measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale
Time Frame: between the baseline and 1,5 years and between the baseline and 2 years
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS scale at an initial distance of 4 meters.
between the baseline and 1,5 years and between the baseline and 2 years
values of Visual Acuity (VA) at each visit
Time Frame: all visits during 2 years
all visits during 2 years
Area under the curve (AUC) of VA
Time Frame: between the baseline and 52 weeks and between the baseline and 2 years
AUC calculated with the values of VA at each visit
between the baseline and 52 weeks and between the baseline and 2 years
Description of Visual acuity (VA)
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
categorized change of VA (>=+15 ; +10 -> +15 ; +5 -> +10 ; -5 -> +5 (stable) ; -5 -> -10 ; -10 -> -15 ; > -15)
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Number of IVI
Time Frame: 1 year
1 year
Number of IVI
Time Frame: 2 years
2 years
OCT parameters: Central Subfield Mean Thickness (CSMT)
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
average, standard deviation, median, minimum and maximum
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters: Central Fovea Thickness
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
average, standard deviation, median, minimum and maximum
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of interruptions of the ellipsoid line
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of continuous external limiting membrane
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the which obtained the BCVA
OCT parameters : presence of disorganization of the internal retinal layers
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of intraretinal cysts
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of vitreomacular traction
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtain the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtain the BCVA
OCT parameters : presence of epiretinal membrane
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of macular exudates
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : persistance of foveolar depression
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA
OCT parameters : presence of intraretinal fluid
Time Frame: at each visit
at each visit
Proportion of patients with macular edema resolution
Time Frame: at 1 year
A macular edema resolution will be defined as absence of intraretinal fluid for at least 6 months after the last
at 1 year
Proportion of patients with macular edema resolution
Time Frame: at 2 years
A macular edema resolution will be defined as absence of intraretinal fluid for at least 6 months after the last
at 2 years
Retinopathy parameters : presence of intraretinal or subretinal macular hemorrhage
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
on stereoscopic 7-field color fundus photographs
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Retinopathy parameters: presence of microaneurisms
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
on stereoscopic 7-field color fundus photographs
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Retinopathy parameters : presence of macular exudates
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
on stereoscopic 7-field color fundus photographs
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Severity evolution (improvement, no change, worsening) of diabetic retinopathy graded by 2 evaluators on stereoscopic 7-field color fundus photographs
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Using the Stadification Diabetic Retinopathy Severity Scale (DRSS), 5 levels: No apparent retinopathy, Mild Non Proliferative Diabetic Retinopathy (NPDR), Moderate NPDR,severe NDPR and Proliferative Diabetic Retinopathy (PDR)
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Quantitative OCT-angiography analysis : the size of non-perfusion zones
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
The mean (and standard deviation) the median (minimum-maximum) of the size of non-perfusion
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Quantitative OCT-angiography analysis : the size of central avascular zones
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
The mean (and standard deviation) the median (minimum-maximum) of the size of central avascular zones compared with baseline
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Qualitative OCT-angiography analysis : presence of macular ischemia
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
the number of macular ischemia
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Qualitative OCT-angiography analysis : Evolution of macular ischemia compared to the baseline
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Types of evolution compared to baseline : appearance / disappearance / stability of the macular ischemia.
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Qualitative OCT-angiography analysis : presence of preretineal neovessels
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
the number of preretineal neovessels,
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Qualitative OCT-angiography analysis : evolution of preretineal neovessels compared to the baseline
Time Frame: Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Types of evolution : appearance / disappearance / stability.
Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years
Biomicroscopy: the number and the percentage by categories of the condition of the implant
Time Frame: all visits during 2 years
conditions : clear, opacified , integrity, open, performed capsulotomy
all visits during 2 years
Biomicroscopy: presence of the state of the posterior capsule
Time Frame: all visits during 2 years
absence or presence of the posterior capsule
all visits during 2 years
Variation of the intraocular pressure
Time Frame: all visits during 2 years
all visits during 2 years
proportion of patients using hypotonic eye treatment
Time Frame: all visits during 2 years
all visits during 2 years
Number of adverse events
Time Frame: all visits during 2 years
All adverse events will be coded using the Meddra system organ class and cases of patients stopping or switching drugs will be described (causes, new drugs,..)
all visits during 2 years
Level of discomfort felt by the patient
Time Frame: all visits during 1 year
Discomfort felt by the patient measured by a visual analog scale (EVA between 0 and 10 (0 = no discomfort))
all visits during 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2020

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

September 16, 2019

First Submitted That Met QC Criteria

October 3, 2019

First Posted (Actual)

October 4, 2019

Study Record Updates

Last Update Posted (Actual)

April 18, 2024

Last Update Submitted That Met QC Criteria

April 16, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL19_0588
  • 2019-003092-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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