A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,151
- 试验地点
- 11
- 主要终点
- Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
研究概览
简要总结
LENS is a streamlined multicentre randomised placebo-controlled parallel-group trial investigating the effect of fenofibrate treatment on the progression of diabetic retinopathy/maculopathy.
详细描述
LENS is a phase 4 randomised placebo-controlled clinical trial of fenofibrate in participants with diabetes and observable retinopathy or maculopathy. The trial aims to recruit approximately 1,060 participants and to treat them for a median duration of at least 4 years. The main aim of LENS is to investigate the effect of fenofibrate therapy on progression to referable diabetic retinopathy/maculopathy. The trial will be conducted using a pragmatic streamlined trial design with the only planned face-to-face visits being an initial screening visit, followed by a randomisation visit eight weeks later. Contact with participants thereafter will be by means of regular telephone or computer questionnaire, and outcome and safety data will also be sought by means of linkage to NHS Scotland registries. Prior to randomisation, eligible participants will enter an active run-in phase of 6 to 10 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Capable of giving informed consent
- •Diabetes Mellitus (any type except gestational diabetes)
- •Observable diabetic retinopathy/maculopathy (defined based on NHS Scotland grading criteria as: R1 in both eyes or R2 in one/both eyes at the most recent retinal screening assessment; or M1 in one/both eyes at any retinal screening assessment in the 3 years)
- •Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months
排除标准
- •Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes)
- •History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy)
- •History of acute or chronic pancreatitis
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range at screening visit
- •ALT or AST >2.5X ULN according to local NHS laboratory reference range at randomisation visit
- •Creatine kinase (CK) >3X ULN according to local NHS laboratory reference range at screening visit
- •CK >3X ULN according to local NHS laboratory reference range at randomisation visit
- •Estimated glomerular filtration rate (eGFR) <40mL/min/1.73m2 at screening visit
- •eGFR <30mL/min/1.73m2 at randomisation visit
- •Cirrhosis of any aetiology or any other serious hepatic disease (investigator opinion)
- •Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practising birth control
- •Ongoing vitamin K antagonist (warfarin, phenindione, acenocoumarol), cyclosporine, colchicine, ketoprofen, daptomycin, fibrate therapy, or treatment with rosuvastatin 40mg daily
- •Previous myositis, myopathy or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder
- •Ongoing renal replacement therapy
- •Any previous organ transplant
- •Previous reported intolerance to any fibrate
- •Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer within last 5 years other than non-melanoma skin cancer; or recent history of alcohol or substance misuse)
- •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
- •LENS participants can participate in other research studies, including clinical trials. The only exclusions related to co-enrolment will be: if any other study or trial excludes co-enrolment or if the intervention being investigated in another trial has the potential to interact with fenofibrate therapy.
- •Not adherent to active run-in treatment
研究组 & 干预措施
Fenofibrate 145 mg
Name: Fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
干预措施: Fenofibrate 145 mg (Drug)
Placebo Oral Tablet
Name: Placebo; Form: tablet; Dosage: not applicable; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
时间窗: 4.0 years (interquartile range, 3.6 to 4.3) years
Primary outcome was a composite of the development of referable diabetic retinopathy or referable maculopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). Referable diabetic retinopathy was defined by the NHS Scotland's grading criteria as any development of R3, R4 or M2 disease. R3 (referable background diabetic retinopathy): any of four or more blot hemorrhages in both inferior and superior hemi-fields, or venous beading, or intraretinal microvascular abnormalities (IRMA); R4 (proliferative diabetic retinopathy): any active new vessels, or vitreous hemorrhage; M2 (referable maculopathy): any blot hemorrhages, or hard exudates within a radius of ≤1 optic disc diameter of the centre of the fovea. Adverse event reports of eye procedures, vitreous haemorrhages and macular oedema were adjudicated by experienced doctors at the Central Co-ordinating Office (CCO), masked to treatment allocation.
次要结局
- Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea)(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants With The Development of Macular Oedema(4.0 years (interquartile range, 3.6 to 4.3) years)
- Visual Acuity(4.0 years (interquartile range, 3.6 to 4.3) years)
- Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25).(4.0 years (interquartile range, 3.6 to 4.3) years)
- Quality of Life, Based on the EQ-5D Index Score(4.0 years (interquartile range, 3.6 to 4.3) years)
- Quality of Life, Based on the EQ-5D Visual Analogue Scale.(4.0 years (interquartile range, 3.6 to 4.3) years)
- Cost to the Health Service(2 years)
- Cost-effectiveness (Incremental Cost Per QALY Gained)(Projected over 10 year horizon)
- Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment(4.0 years (interquartile range, 3.6 to 4.3) years)
- Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization(Up to 1 year from randomisation.)
- Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization(4.0 years (interquartile range, 3.6 to 4.3) years, excluding any primary outcome events within the first year of randomisation.)