Clinical trial NCT03439345: Lowering Events in Non-proliferative Retinopathy in Scotland
Official title: A Randomised Placebo-controlled Trial of Fenofibrate to Prevent Progression of Non-proliferative Retinopathy in Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Retinopathy
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
name: University of Glasgow
name: University of Aberdeen
name: University of Dundee
name: University of Edinburgh
name: NHS Scotland Diabetic Retinopathy Screening Collaborative
First posted: 2018-02-20
Enrollment: 1151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: LENS is a streamlined multicentre randomised 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 randomisation, eligible participants will enter an active run-in phase of 6 to 10 weeks.

Eligibility criteria: 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

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

Primary outcomes:
measure: Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
Secondary outcomes:
measure: Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea)
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With The Development of Macular Oedema
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Visual Acuity
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25).
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Quality of Life, Based on the EQ-5D Index Score
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Quality of Life, Based on the EQ-5D Visual Analogue Scale.
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Cost to the Health Service
timeFrame: 2 years
measure: Cost-effectiveness (Incremental Cost Per QALY Gained)
timeFrame: Projected over 10 year horizon
measure: Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization
timeFrame: Up to 1 year from randomisation.
measure: Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years, excluding any primary outcome events within the first year of randomisation.
Other outcomes:
measure: Percentage Change in Urine Albumin:Creatinine Ratio
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With Occurrence of Major Cardiovascular Events (Myocardial Infarction, Stroke, Coronary or Peripheral Revascularisation)
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
measure: Number of Participants With Occurrence of Non-traumatic Lower Limb Amputations
timeFrame: 4.0 years (interquartile range, 3.6 to 4.3) years
Locations:
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
city: Airdrie
country: United Kingdom
facility: NHS Lanarkshire
city: Ayr
country: United Kingdom
facility: NHS Ayrshire and Arran
city: Dumfries
country: United Kingdom
facility: NHS Dumfries and Galloway
city: Dundee
country: United Kingdom
facility: NHS Tayside
city: Dunfermline
country: United Kingdom
facility: NHS Fife
city: East Kilbride
country: United Kingdom
facility: NHS Lanarkshire
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Inverness
country: United Kingdom
facility: NHS Highland
city: Kilmarnock
country: United Kingdom
facility: NHS Ayrshire and Arran
city: Kirkcaldy
country: United Kingdom
facility: NHS Fife
city: Larbert
country: United Kingdom
facility: NHS Forth Valley
city: Melrose
country: United Kingdom
facility: NHS Borders
city: Perth
country: United Kingdom
facility: NHS Tayside
city: Wishaw
country: United Kingdom
facility: NHS Lanarkshire
Study officials:
affiliation: University of Oxford
name: David Preiss, PhD FRCPath
role: PRINCIPAL_INVESTIGATOR
References:
citation: LENS Collaborative Group. Design, recruitment and baseline characteristics of the LENS trial. Diabet Med. 2024 Sep;41(9):e15310. doi: 10.1111/dme.15310. Epub 2024 Feb 22.
citation: Preiss D, Logue J, Sammons E, Zayed M, Emberson J, Wade R, Wallendszus K, Stevens W, Cretney R, Harding S, Leese G, Currie G, Armitage J. Effect of Fenofibrate on Progression of Diabetic Retinopathy. NEJM Evid. 2024 Aug;3(8):EVIDoa2400179. doi: 10.1056/EVIDoa2400179. Epub 2024 Jun 21.