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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04116398
Recruitment Status : Not yet recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

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 3 months, followed by a PRN (Pro Re Nata) regimen with strict retreatment criteria and minimal time limit of 3 months 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.


Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Drug: Dexamethasone with 2 loading doses followed by PRN regimen. Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema

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®; 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 : 3 months
  • Visits: monthly during 1 year (to check efficacy and safety) and then for the 2nd-year only at Month18 (M18) and Month 24 (M24)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. The time required to obtain the best BCVA [ Time Frame: 52 weeks ]
    average, standard deviation, median, minimum and maximum

  2. The number of injections required to obtain the best BCVA [ Time Frame: 52 weeks ]
    average, standard deviation, median, minimum and maximum

  3. 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.

  4. values of Visual Acuity (VA) at each visit [ Time Frame: all visits during 2 years ]
  5. 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

  6. 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)

  7. Number of IVI [ Time Frame: 1 year ]
  8. Number of IVI [ Time Frame: 2 years ]
  9. 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

  10. 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

  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. OCT parameters : presence 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 ]
  19. OCT parameters : presence of intraretinal fluid [ Time Frame: at each visit ]
  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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)

  26. Quantitative OCT-angiography analysis : the size of non-perfusion zones [ Time Frame: all visits during 2 years ]
    The mean (and standard deviation) the median (minimum-maximum) of the size of non-perfusion

  27. Quantitative OCT-angiography analysis : the size of central avascular zones [ Time Frame: all visits during 2 years ]
    The mean (and standard deviation) the median (minimum-maximum) of the size of central avascular zones compared with baseline

  28. Qualitative OCT-angiography analysis : presence of macular ischemia [ Time Frame: all visits during 2 years ]
    the number of macular ischemia

  29. Qualitative OCT-angiography analysis : Evolution of macular ischemia compared to the baseline [ Time Frame: all visits during 2 years ]
    Types of evolution compared to baseline : appearance / disappearance / stability of the macular ischemia.

  30. Qualitative OCT-angiography analysis : presence of preretineal neovessels [ Time Frame: all visits during 2 years ]
    the number of preretineal neovessels

  31. Qualitative OCT-angiography analysis : evolution of preretineal neovessels compared to the baseline [ Time Frame: all visits during 2 years ]
    Types of evolution : appearance / disappearance / stability.

  32. 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

  33. Biomicroscopy: presence of the state of the posterior capsule [ Time Frame: all visits during 2 years ]
    absence or presence of the posterior capsule

  34. Variation of the intraocular pressure [ Time Frame: all visits during 2 years ]
  35. proportion of patients using hypotonic eye treatment [ Time Frame: all visits during 2 years ]
  36. 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,..)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) ≥ 310 μm measured on Spectralis or ≥ 300 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, intraocular implant with iris fixated or transsclerally and and 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 < 6 months in the study eye
  • Delay after last session of panretineal Photocoagulation laser < 3 months in the study eye
  • Delay after last focal laser session of the posterior pole < 3 months 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
  • 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
  • Man or woman of child-bearing age, sexually active, who does not want to commit to using adequate contraception during the study
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116398


Contacts
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Contact: Laurent KODJIKIAN +33 4 26 10 93 21 laurent.kodjikian@chu-lyon.fr
Contact: Christelle Szatanek +33 4 26 73 27 24 christelle.szatanek@chu-lyon.fr

Locations
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France
Hospices Civils de Lyon - Hopital de la Croix Rousse
Lyon, France, 69004
Contact: Laurent KODJIKIAN    04 26 10 93 21    laurent.kodjikian@chu-lyon.fr   
Contact: Christelle Szatanek    +33 4 26 73 27 24    christelle.szatanek@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04116398    
Other Study ID Numbers: 69HCL19_0588
2019-003092-18 ( EudraCT Number )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
dexamethasone,
loading dose,
diabetic macular edema
pseudophakic
Additional relevant MeSH terms:
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Macular Edema
Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action