Phase 4
N=1,151
Lowering Events in Non-proliferative Retinopathy in Scotland
Diabetic Retinopathy
Bottom Line
View on ClinicalTrials.gov: NCT03439345 ↗Enrolled (actual)
1,151
Serious AEs
35.8%
Results posted
May 2025
Primary outcome: Primary: Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment — 131; 168 Participants — p=0.006
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Fenofibrate 145 mg (Drug); Placebo Oral Tablet (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of Oxford
- Primary completion
- Nov 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
131; 168 | 0.006 sig |
| SECONDARY Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy |
130; 168 | 0.005 sig |
| SECONDARY Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy |
17; 28 | 0.08 |
| SECONDARY Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale |
185; 231 | 0.003 sig |
| SECONDARY Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea) |
107; 149 | 0.001 sig |
| SECONDARY Number of Participants With The Development of Macular Oedema |
22; 43 | 0.008 sig |
| SECONDARY Visual Acuity |
0.06; 0.05 | 0.36 |
| SECONDARY Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25). |
90; 89 | 0.58 |
| SECONDARY Quality of Life, Based on the EQ-5D Index Score |
0.75; 0.75 | 0.93 |
| SECONDARY Quality of Life, Based on the EQ-5D Visual Analogue Scale. |
75; 76 | 0.43 |
| SECONDARY Cost to the Health Service |
3566; 3820 | — |
| SECONDARY Cost-effectiveness (Incremental Cost Per QALY Gained) |
5.434; 5.419 | — |
| SECONDARY Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
99; 121 | — |
| SECONDARY Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
32; 47 | — |
| SECONDARY Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
68; 93 | — |
| SECONDARY Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment. |
63; 75 | — |
| SECONDARY Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
38; 45 | — |
| SECONDARY Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
93; 123 | — |
| SECONDARY Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
17; 32 | — |
| SECONDARY Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
114; 136 | — |
| SECONDARY Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
63; 81 | — |
| SECONDARY Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
57; 79 | — |
| SECONDARY Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment |
11; 8 | — |
| SECONDARY Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization |
45; 63 | — |
| SECONDARY Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization |
86; 105 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03439345). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.