Lowering Events in Non-proliferative Retinopathy in Scotland

Study Overview
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Brief Summary
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LENS is a streamlined multicentre randomized placebo-controlled parallel-group trial investigating the effect of fenofibrate treatment on the progression of diabetic retinopathy/maculopathy

Detailed Description
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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 randomization, eligible participants will enter an active run-in phase of 6 to 10 weeks.

Official Title
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A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: Fenofibrate 145 mg
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fenofibrate 145 mg<br>Name: fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: one tablet daily with normal renal function, one tablet every 2nd day with chronic kidney disease | Drug: Fenofibrate 145 mg<br>* One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)<br>|
| Placebo Comparator: Placebo Oral Tablet<br>Name: placebo; Form: tablet; Dosage: not applicable; Frequency: one tablet daily with normal renal function, one tablet every 2nd day with chronic kidney disease | Drug: Placebo Oral Tablet<br>* One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression to referable diabetic retinopathy/maculopathy | The composite of progression to referable diabetic retinopathy/maculopathy or any of retinal laser therapy, vitrectomy or intra-vitreal injection of medication for the treatment of diabetic retinopathy/maculopathy Referable diabetic retinopathy is defined according to NHS Scotland's grading criteria. | Approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Components of the primary outcome (progression to referable diabetic retinopathy/maculopathy; retinal laser therapy; vitrectomy; intra-vitreal injection of medication for treatment of diabetic retinopathy/maculopathy) reported separately | Number of participants, respectively, in whom the following outcomes occur, reported separately: Number of participants with progression of diabetic retinopathy/maculopathy to referable diabetic retinopathy/maculopathy (based on the NHS Scotland grading scheme) Number of participants requiring retinal laser therapy for diabetic retinopathy/maculopathy (based on patient report and health records) Number of participants requiring vitrectomy for diabetic retinopathy/maculopathy (based on the NHS patient report and health records) Number of participants requiring intra-vitreal injection for diabetic retinopathy/maculopathy (based on the NHS patient report and health records) | Approximately 4 years | 
| Any progression of diabetic retinopathy/maculopathy | Based on the NHS Scotland grading scheme | Approximately 4 years | 
| Visual acuity | Based on measurement of visual acuity at retinal screening visits | Approximately 4 years | 
| The development of hard exudates or haemorrhages within 1 disc diameter of the macula | Based on the NHS Scotland grading scheme | Approximately 4 years | 
| The development of macular oedema | The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report | Approximately 4 years | 
| Visual function (according to the VFQ-25 questionnaire) | According to the VFQ-25 questionnaire | Approximately 4 years | 
| Quality of life (according to the EQ-5D questionnaire) | According to the EQ-5D questionnaire | Approximately 4 years | 
| Total cost to the health service | Health economic analysis | Approximately 4 years | 
| Cost-effectiveness (incremental cost per QALY gained) | Health economic analysis | Approximately 4 years |