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Lowering Events in Non-proliferative Retinopathy in Scotland

Phase 4
Completed
Conditions
Diabetic Retinopathy
Interventions
Drug: Fenofibrate 145 mg
Drug: Placebo Oral Tablet
Registration Number
NCT03439345
Lead Sponsor
University of Oxford
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1151
Inclusion Criteria
  1. Capable of giving informed consent
  2. Diabetes Mellitus (any type except gestational diabetes)
  3. 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)
  4. Willing to either complete electronic questionnaires or conduct telephone interviews for collection of data once every 6 months
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Exclusion Criteria
  1. Clinically significant DR (defined as R3 or R4 or M2 in one or both eyes)
  2. History of gallbladder disease (cholecystitis, symptomatic gallstones, cholecystectomy)
  3. History of acute or chronic pancreatitis
  4. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2X the upper limit of normal (ULN) according to local NHS laboratory reference range at screening visit
  5. ALT or AST >2.5X ULN according to local NHS laboratory reference range at randomisation visit
  6. Creatine kinase (CK) >3X ULN according to local NHS laboratory reference range at screening visit
  7. CK >3X ULN according to local NHS laboratory reference range at randomisation visit
  8. Estimated glomerular filtration rate (eGFR) <40mL/min/1.73m2 at screening visit
  9. eGFR <30mL/min/1.73m2 at randomisation visit
  10. Cirrhosis of any aetiology or any other serious hepatic disease (investigator opinion)
  11. Female who is pregnant, breastfeeding, currently trying to become pregnant, or of child-bearing potential and not practising birth control
  12. Ongoing vitamin K antagonist (warfarin, phenindione, acenocoumarol), cyclosporine, colchicine, ketoprofen, daptomycin, fibrate therapy, or treatment with rosuvastatin 40mg daily
  13. Previous myositis, myopathy or rhabdomyolysis of any cause, or diagnosed hereditary muscle disorder
  14. Ongoing renal replacement therapy
  15. Any previous organ transplant
  16. Previous reported intolerance to any fibrate
  17. 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)
  18. 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
  19. 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.
  20. Not adherent to active run-in treatment
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fenofibrate 145 mgFenofibrate 145 mgName: fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: one tablet daily with normal renal function, one tablet every 2nd day with chronic kidney disease
Placebo Oral TabletPlacebo Oral TabletName: placebo; Form: tablet; Dosage: not applicable; Frequency: one tablet daily with normal renal function, one tablet every 2nd day with chronic kidney disease
Primary Outcome Measures
NameTimeMethod
Progression to referable diabetic retinopathy/maculopathyApproximately 4 years

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.

Secondary Outcome Measures
NameTimeMethod
Visual acuityApproximately 4 years

Based on measurement of visual acuity at retinal screening visits

The development of hard exudates or haemorrhages within 1 disc diameter of the maculaApproximately 4 years

Based on the NHS Scotland grading scheme

The development of macular oedemaApproximately 4 years

The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report

Quality of life (according to the EQ-5D questionnaire)Approximately 4 years

According to the EQ-5D questionnaire

Total cost to the health serviceApproximately 4 years

Health economic analysis

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 separatelyApproximately 4 years

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)

Any progression of diabetic retinopathy/maculopathyApproximately 4 years

Based on the NHS Scotland grading scheme

Visual function (according to the VFQ-25 questionnaire)Approximately 4 years

According to the VFQ-25 questionnaire

Cost-effectiveness (incremental cost per QALY gained)Approximately 4 years

Health economic analysis

Trial Locations

Locations (11)

NHS Lothian

🇬🇧

Edinburgh, United Kingdom

NHS Grampian

🇬🇧

Aberdeen, United Kingdom

NHS Dumfries and Galloway

🇬🇧

Dumfries, United Kingdom

NHS Lanarkshire

🇬🇧

Wishaw, United Kingdom

NHS Borders

🇬🇧

Melrose, United Kingdom

NHS Ayrshire and Arran

🇬🇧

Kilmarnock, United Kingdom

NHS Fife

🇬🇧

Kirkcaldy, United Kingdom

NHS Greater Glasgow and Clyde

🇬🇧

Glasgow, United Kingdom

NHS Forth Valley

🇬🇧

Larbert, United Kingdom

NHS Tayside

🇬🇧

Perth, United Kingdom

NHS Highland

🇬🇧

Inverness, United Kingdom

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