Combined Anti-VEGF Intravitreal Injections With Sustained Steroid Implantation for the Treatment of Diabetic Macular Oedema
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Number of Lucentis Injections received in the study eye
研究概览
简要总结
This trial investigated whether adding Iluvien sustained release steroid intravitreal eye implant at the beginning of regular anti-VEGF (anti Vascular Endothelial Growth Factor) intravitreal eye injection treatment for diabetic macular oedema would improve disease stability and reduce the need for regular anti-VEGF intravitreal eye injections over first two years. Diabetic macular oedema, accumulation of microscopic fluid at the back of the eye, is a major cause of poor vision in patients with diabetes.
This is a double mask randomized control multisite trial, to be conducted at 10 NHS hospital eye clinics in England.
详细描述
This study will recruit 58 participants in a double-masked, multi-centre, sham-controlled clinical trial. Participants will receive Iluvien implantation or sham implantation (masked) with a concomitant intravitreal injection of ranibizumab at baseline with an allocation ratio of 1:1. This is followed by regular monthly clinic review and repeat intravitreal ranibizumab injections to the study eye according to a PRN (pro re nata) treatment protocol.
This trial aims to evaluate whether Iluvien implantation in addition to standard anti-VEGF injection treatment for diabetic macular oedema in pseudophakic eyes will show similar visual acuity outcomes but with an improved reduction in CRT (Central Retinal Thickness) while reducing the average number of intravitreal injections during the first 2 years of treatment, due to the continual micro-dosing of Iluvien therapy.
Participants meeting all the eligibility criteria will be randomized to either Iluvien implant or sham implant procedure with an allocation ratio of 1:1. Participants assigned to either treatment arms will receive intravitreal injection of ranibizumab after Iluvien implantation or sham implantation at the same baseline visit.
To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug. Patients assigned to either treatment arm will receive ranibizumab intravitreal injection to the study eye at baseline 30 minutes after the Iluvien or sham implantation. The sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.
Participants will be followed up monthly for 2 years. Participants from both arms will receive compulsory Ranibizumab injection during the first three monthly visit and followed by monthly Ranibizumab as per PRN protocol. The end of study visit should take place at 104 weeks from the baseline visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
To maintain double-masking, participants assigned to the control arm will receive sham implantation. This will be performed with an empty Luer Lock Syringe without a needle attached to it, that will not penetrate the eye nor deliver any drug.
The Iluvien and the sham injection should be performed by the unmasked investigator. The unmasked investigator should not be involved in any patient assessment in the study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness and the ability to provide informed consent.
- •Ability and willingness to undertake all scheduled visits, assessment and treatment.
- •Age 18 years or above.
- •Documented diagnosis of diabetes mellitus (Type I or Type II) as per WHO (World Health Organization) criteria.
- •Current regular use of oral anti-hyperglycaemia or insulin therapy.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of <1% per year during the study duration of 24 months.
- •Macular thickening due to Diabetic Macular Oedema (DMO) involving the centre of fovea as measured by Spectral Domain OCT with CRT of at least 400 microns.
- •DMO confirmed by clinical examination and fundus fluorescein angiography.
- •BCVA between 73 to 25 letters inclusive (Snellen equivalent to 6/12 to 6/96) as measured using ETDRS protocol at 4 meters.
- •Pseudophakia in the study eye.
- •Adequate ocular media clarity and pupillary dilatation allowing for posterior segment examination and OCT scanning.
排除标准
- •Cerebral vascular accident, transient ischaemic attack or myocardial infarction within 3 months prior to day 1 (baseline).
- •Pregnancy or breastfeeding, or intention to become pregnant during the study.
- •Participation in an investigational trial involving treatment with any drug or devices within 3 months prior to day 1 (baseline) and must not be enrolled in another investigational trial during their participation in this trial.
- •Systemic anti-VEGF-base therapies within 3 months prior to day 1 (baseline).
- •History of prior intravitreal anti-VEGF therapy or steroid implant in the study eye.
- •History of proliferative diabetic retinopathy.
- •History of rubeosis or current rubeosis.
- •History of neovascularization, tractional retinal detachment, retinal vein occlusion, or significant pre-retinal fibrosis distorting the macular architecture.
- •History of retinal detachment or macular hole stage 3 or above.
- •History of vitreoretinal surgery.
- •History of glaucoma or uncontrolled ocular hypertension.
- •Active or suspected ocular or periocular infection or inflammation, including viral diseases of the cornea, conjunctiva and retina, such as active epithelial herpes simplex keratitis (dendritic keratitis), varicella, mycobacterial infections, and fungal diseases.
- •Panretinal Photocoagulation (PRP) laser treatment within 3 months prior to day
- •Macular laser (focal or grid) within 3 months prior to day
- •YAG (yttrium aluminium garnet) laser capsulotomy laser within 3 months prior to day
- •Any periocular steroid treatment within 6 months prior to day
- •Cataract operation within 3 months prior to day 1.
研究组 & 干预措施
Iluvien Arm
Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
干预措施: Iluvien 0.19 MG Drug Implant (Drug)
Iluvien Arm
Participants assigned to the Iluvien treatment arm will receive Iluvien 0.19 MG Drug Implant to the study eye under aseptic condition at baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
干预措施: Ranibizumab Injection [Lucentis] (Drug)
Control Arm
To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
干预措施: Ranibizumab Injection [Lucentis] (Drug)
Control Arm
To maintain double-masking, participants assigned to the control arm will receive Sham Intravitreal Injection at the baseline visit with monthly Ranibizumab Injection [Lucentis] for first three visits followed by monthly Ranibizumab Injection [Lucentis] PRN.
干预措施: Sham Intravitreal Injection (Procedure)
结局指标
主要结局
Number of Lucentis Injections received in the study eye
时间窗: 24 months
The total number of Lucentis injections needed over 24 months following the intravitreal injection PRN protocol
次要结局
- Maintaining at least 20/40 vision(Month 24)
- Change in visual acuity(Month 24)
- Proportion of participants with vision loss(Month 24)
- Proportion of participants with visual gain(Month 24)
- Stability of vision(Over 24 months)
- Central retinal thickness(Month 24)
- CRT stability(Over 24 months)
- Retinal thickness variability(Over 24 months)
- Change in Diabetic Retinopathy Severity(Between baseline and month 24)
- Number of focal laser treatments(Over 24 months)