NCT04116398已完成2 期
Pilot and Phase 2 Study of the Efficacy of a Treatment Protocol With Dexamethasone Implant Loading Dose in Patients With Diabetic Macular Edema
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 29
- 主要终点
- Maximum BCVA (Best Corrected Visual Acuity) change (best improvement) from baseline (during one year of treatment)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Ozurdex®, 700µg dexamethasone intravitreal injection
Experimental
Intravitreal injection of dexamethasone (Ozurdex®)
干预措施: Dexamethasone with 2 loading doses followed by PRN regimen. (Drug)
结局指标
主要结局
Maximum BCVA (Best Corrected Visual Acuity) change (best improvement) from baseline (during one year of treatment)
时间窗: 52 weeks
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS scale at an initial distance of 4 meters.
Difference between the highest value of Best Corrected Visual Acuity (BCVA) observed during follow-up to 52 weeks and the BCVA observed at inclusion (best observed improvement). Corrected visual acuity will be measured as the number of letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at an initial distance of 4 meters.
Difference between the highest value of Best Corrected Visual Acuity (BCVA) observed during follow-up to 52 weeks and the BCVA observed at inclusion (best observed improvement). Corrected visual acuity will be measured as the number of letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale at an initial distance of 4 meters.
次要结局
- OCT parameters : presence of continuous external limiting membrane(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(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(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA)
- The time required to obtain the best BCVA(52 weeks)
- The number of injections required to obtain the best BCVA(52 weeks)
- the maximum best corrected visual acuity (BCVA) change (best improvement) measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale(between the baseline and 1,5 years and between the baseline and 2 years)
- values of Visual Acuity (VA) at each visit(all visits during 2 years)
- Area under the curve (AUC) of VA(between the baseline and 52 weeks and between the baseline and 2 years)
- Description of Visual acuity (VA)(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 years, 2 years and the visit which obtained the BCVA)
- Number of IVI(1 year)
- Number of IVI(2 years)
- OCT parameters: Central Subfield Mean Thickness (CSMT)(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(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(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(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(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(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(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(at each visit)
- Proportion of patients with macular edema resolution(at 1 year)
- Proportion of patients with macular edema resolution(at 2 years)
- Retinopathy parameters : presence of intraretinal or subretinal macular hemorrhage(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years)
- Retinopathy parameters: presence of microaneurisms(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years)
- Retinopathy parameters : presence of macular exudates(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(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(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(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years)
- Qualitative OCT-angiography analysis : presence 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(Baseline, 12 weeks, 24 weeks,36 weeks,52 weeks, 1.5 year and 2 years)
- Qualitative OCT-angiography analysis : presence 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(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(all visits during 2 years)
- Biomicroscopy: presence of the state of the posterior capsule(all visits during 2 years)
- Variation of the intraocular pressure(all visits during 2 years)
- proportion of patients using hypotonic eye treatment(all visits during 2 years)
- Number of adverse events(all visits during 2 years)
- Level of discomfort felt by the patient(all visits during 1 year)
- Describe the time required to reach the highest MAVC value during the first 52 weeks, as well as the number of injections.
- Description of VA by : oDifference between the highest value of BCVA observed up to M18 and up to M24 and the value at inclusion. Corrected VA measured on the ETDRS scale; o VA value at each visit (monthly for the 1st year) and area under the curve between inclusion and S52 and between inclusion and M24; o At S12,S24,S36,S52,M18 and M24, as well as for the highest CVAM observed in 52 weeks: proportion of patients by CVAM change category (cf protocole)
- Total number of injections performed per patient at S52 and M24.
- Patient discomfort related to the intravitreal implant, measured by a visual analog scale (VAS between 0 and 10) at each visit between S0 and S52.
- At S12,S24,S36,S52,M18 and M24; as well as for the visit at which the best improvement over 52 weeks is observed: Variation in CMT and central foveolar thickness and qualitative analysis of each OCT (from a central section of the fovea: presence of interruptions of the ellipsoid, outer limiting membrane, intraretinal cysts or logettes, presence of disorganized inner retinal layers, subretinal fluid, foveolar depression, epiretinal membrane, vitreo-macular traction and macular exudates).
- Proportion of patients with resolution of macular oedema (defined as absence of intraretinal fluid 6 months or more after the last injection) at S52 and M24.
- At S12, S24, S36, S52, M18 and M24, the number and percentage of patients with each grade of diabetic retinopathy according to the Staging DRSS will be calculated: improvement (gain of 2 levels or gain of 3 levels), no change, or worsening (loss of 2 levels or loss of 3 levels); between inclusion and S12, S24, S36, S52, M18 and M24, according to a centralised review on colour fundus photographs including at least the 7 ETDRS fields i.e. 30 degrees.
- At S12, S24, S36, S52, M18 and M24: qualitative and quantitative analysis of diabetic vascularisation and non-perfusion zones on OCT-angiography (size of capillary non-perfusion zones, size of central avascular zone, presence of macular ischaemia) according to a centralised reading
- At each visit: condition of lens implant and posterior chamber determined by biomicroscopy with fundus.
- Change in intraocular pressure between inclusion and S52, and between inclusion and M24, and proportion of patients using hypotonising therapy for 24 months.
- Adverse events observed throughout the study: o Frequency of ocular prognostic adverse events: see protocol o Incidence of non-ocular life-threatening adverse events: see protocol o Incidence of systemic adverse events: see protocol
研究者
研究点 (29)
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