A Phase 4 interventional study of Fenofibrate 145 mg and Placebo Oral Tablet in Diabetic Retinopathy, sponsored by University of Oxford. Completed at 16 sites in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-14.
Sponsored by University of Oxford · Phase 4, Interventional, and Treatment
LENS is a streamlined multicentre randomised placebo-controlled parallel-group trial investigating the effect of fenofibrate treatment on the progression of diabetic retinopathy/maculopathy.
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.
778 studies on the registry are indexed under Diabetic Retinopathy; 142 are open to participants now.
This study's enrollment of 1,151 is above the median of 80 across 481 interventional studies indexed under Diabetic Retinopathy.
Browse Diabetic Retinopathy studies →University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Name: Fenofibrate; Form: tablet; Dosage: 145 mg; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
Drug: Fenofibrate 145 mg
Name: Placebo; Form: tablet; Dosage: not applicable; Frequency: One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
Drug: Placebo Oral Tablet
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
One tablet (taken daily with normal renal function, taken every second day with chronic kidney disease)
Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
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.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy
Progression of Diabetic Retinopathy/Maculopathy to a referable grade (R3 or R4 or M2) based on the NHS Scotland grading scheme in at least one eye.
Time frame: 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
Treatment for diabetic retinopathy or maculopathy (including intravitreal injection of medication, retinal laser therapy, or vitrectomy) in either eye.
Time frame: 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
Any progression of diabetic retinopathy or maculopathy across the NHS Scotland retinopathy grading scale. R4 = Proliferative DR, R3 = Referable background DR, R2 = Observable background DR. R1 = Mild background DR, R0 = No DR anywhere (where R4 is the highest severity grade and R0 is the lowest grade); M2 = Referable maculopathy, M1 = Observable maculopathy, M0 = No Maculopathy (where M2 is the highest severity grade and M0 is the lowest grade).
Time frame: 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)
The presence of hard exudates or blot haemorrhages within 1 disc diameter of the macula/fovea
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With The Development of Macular Oedema
The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Visual Acuity
Based on measurement of visual acuity at retinal screening visits. Baseline visual acuity was taken from routine measurement within NHS Scotland's Diabetic Eye Screening programme (using the latest value within 18 months of randomisation). Visual acuity after randomisation was obtained by averaging available results for a participant. Conversion from Snellen to LogMAR was applied where necessary. This analysis is based on the better eye: if only 1 eye with results, analyse that eye; if 2 eyes, use eye with better acuity; if identical acuity in both eyes, use the right eye. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision). Lower scores indicate better vision.
Time frame: 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).
Visual function is based on the Visual Function Questionnaire-25. Visual function was defined by the composite score derived from the VFQ-25. VFQ-25 data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. The VFQ-25 composite score ranges from 0 to 100, where higher scores indicate better visual function. It is calculated by averaging results from up to 11 vision-related sub-scales.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Index Score
Quality of life was measured using the EQ-5D instrument, and valued by mapping to the EQ-5D-3L UK value set using the mapping function developed by Hernandez Alava et al. Pharmaco Economics (2022). EQ-5D data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. Possible scores range from -0.59 to 1.00, where 1 is the best possible health state and 0 represents a quality of life considered equivalent to death.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Quality of Life, Based on the EQ-5D Visual Analogue Scale.
EQ-5D Visual Analogue Scale data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. EQ VAS scores range from 0 to 100, where 100 is the best possible health state.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Cost to the Health Service
Health economic analysis: cost to the health service over 2 years. This included (i) hospital inpatient and outpatient activity (costed with nationally representative NHS costs); (ii) costs of fenofibrate (based on 200mg NHS cost); (iii) laboratory tests (NHS cost (including nurse/doctor time)); (iv) community prescribed medicines (NHS costs); (v) NHS Scotland retinal screening (published NHS unit costs); (vi) treatment for advanced retinopathy: for relevant participants, application of assumptions regarding usual number of injections from UK cohort study.
Time frame: 2 years
Cost-effectiveness (Incremental Cost Per QALY Gained)
Health economic analysis: Cost-effectiveness (incremental cost per QALY gained). The result is the value of GBP (British Pound) expenditure required to gain 1 quality adjusted life year for fenofibrate therapy vs. standard care. Years gained are presented by arm with 95% credible intervals taken as 2.5th and 97.5th percentile of simulated probabilistic output.
Time frame: Projected over 10 year horizon
Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - male. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - female. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age \<60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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.
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age ≥60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type of Diabetes - type 1 diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type 2 and other diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR \<60mL/min/1.73m\^2). The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR ≥60mL/min/1.73m\^2. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Primary outcome in prespecified subgroup according to the baseline characteristic: HbA1c at Screening \<70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Primary outcome in prespecified subgroup according to the baseline characteristic-HbA1c at Screening - ≥70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic - HbA1c at Screening - Unknown. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing of primary outcome - Within first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 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
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing - After first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years, excluding any primary outcome events within the first year of randomisation.
Percentage Change in Urine Albumin:Creatinine Ratio
Based on collection of biochemical data. Urine albumin: creatinine ratio (UACR) results. Urine was collected for measurement of UACR at LENS screening visits wherever possible (baseline results). Post randomization UACR results came from measurements conducted part of routine care. Post randomisation results for a participant were averaged for each participant. Separate values for participants assigned fenofibrate and placebo are reported as geometric mean (95% confidence intervals) and the difference between arms is reported as a percentage difference (95% confidence intervals)
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Occurrence of Major Cardiovascular Events (Myocardial Infarction, Stroke, Coronary or Peripheral Revascularisation)
This outcome is a composite of myocardial infarction, stroke, coronary artery revascularisation and peripheral artery revascularisation.
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
Number of Participants With Occurrence of Non-traumatic Lower Limb Amputations
Composite of any non-traumatic lower limb amputation (defined as minor amputation \[distal to the ankle\] or major amputation \[through or proximal to the ankle\]).
Time frame: 4.0 years (interquartile range, 3.6 to 4.3) years
| Milestone | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Started | 576 | 575 |
| Completed | 576 | 573 |
| Not completed | 0 | 2 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Withdrew: Consent withdrawn | 0 | 1 |
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.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 131 | 168 |
Progression of Diabetic Retinopathy/Maculopathy to a referable grade (R3 or R4 or M2) based on the NHS Scotland grading scheme in at least one eye.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With the Individual Component of the Composite Primary Outcome: Development of Referable Diabetic Retinopathy or Maculopathy | 130 | 168 |
Treatment for diabetic retinopathy or maculopathy (including intravitreal injection of medication, retinal laser therapy, or vitrectomy) in either eye.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With the Individual Component of Composite Primary Outcome: Treatment for Diabetic Retinopathy or Maculopathy | 17 | 28 |
Any progression of diabetic retinopathy or maculopathy across the NHS Scotland retinopathy grading scale. R4 = Proliferative DR, R3 = Referable background DR, R2 = Observable background DR. R1 = Mild background DR, R0 = No DR anywhere (where R4 is the highest severity grade and R0 is the lowest grade); M2 = Referable maculopathy, M1 = Observable maculopathy, M0 = No Maculopathy (where M2 is the highest severity grade and M0 is the lowest grade).
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With Any Progression of Diabetic Retinopathy or Maculopathy Across the NHS Scotland Retinopathy Grading Scale | 185 | 231 |
The presence of hard exudates or blot haemorrhages within 1 disc diameter of the macula/fovea
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With Referable Maculopathy (Exudates or Blot Haemorrhages Within One Disc Diameter of the Fovea) | 107 | 149 |
The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With The Development of Macular Oedema | 22 | 43 |
Based on measurement of visual acuity at retinal screening visits. Baseline visual acuity was taken from routine measurement within NHS Scotland's Diabetic Eye Screening programme (using the latest value within 18 months of randomisation). Visual acuity after randomisation was obtained by averaging available results for a participant. Conversion from Snellen to LogMAR was applied where necessary. This analysis is based on the better eye: if only 1 eye with results, analyse that eye; if 2 eyes, use eye with better acuity; if identical acuity in both eyes, use the right eye. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision). Lower scores indicate better vision.
| LogMAR | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Visual Acuity | 0.06 (0.05 to 0.07) | 0.05 (0.05 to 0.06) |
Visual function is based on the Visual Function Questionnaire-25. Visual function was defined by the composite score derived from the VFQ-25. VFQ-25 data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. The VFQ-25 composite score ranges from 0 to 100, where higher scores indicate better visual function. It is calculated by averaging results from up to 11 vision-related sub-scales.
| score on a scale | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Visual Function, Based on the National Eye Institute Visual Functioning Questionnaire 25 (VFQ-25). | 90 (89 to 91) | 89 (89 to 90) |
Quality of life was measured using the EQ-5D instrument, and valued by mapping to the EQ-5D-3L UK value set using the mapping function developed by Hernandez Alava et al. Pharmaco Economics (2022). EQ-5D data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. Possible scores range from -0.59 to 1.00, where 1 is the best possible health state and 0 represents a quality of life considered equivalent to death.
| score on a scale | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Quality of Life, Based on the EQ-5D Index Score | 0.75 (0.73 to 0.76) | 0.75 (0.74 to 0.76) |
EQ-5D Visual Analogue Scale data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. EQ VAS scores range from 0 to 100, where 100 is the best possible health state.
| score on a scale | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Quality of Life, Based on the EQ-5D Visual Analogue Scale. | 75 (74 to 76) | 76 (75 to 77) |
Health economic analysis: cost to the health service over 2 years. This included (i) hospital inpatient and outpatient activity (costed with nationally representative NHS costs); (ii) costs of fenofibrate (based on 200mg NHS cost); (iii) laboratory tests (NHS cost (including nurse/doctor time)); (iv) community prescribed medicines (NHS costs); (v) NHS Scotland retinal screening (published NHS unit costs); (vi) treatment for advanced retinopathy: for relevant participants, application of assumptions regarding usual number of injections from UK cohort study.
| GBP (British Pounds) | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Cost to the Health Service | 3566 (3088 to 4364) | 3820 (3052 to 4749) |
Health economic analysis: Cost-effectiveness (incremental cost per QALY gained). The result is the value of GBP (British Pound) expenditure required to gain 1 quality adjusted life year for fenofibrate therapy vs. standard care. Years gained are presented by arm with 95% credible intervals taken as 2.5th and 97.5th percentile of simulated probabilistic output.
| Years gained | Fenofibrate 145mg | Placebo Oral Tablet |
|---|---|---|
| Cost-effectiveness (Incremental Cost Per QALY Gained) | 5.434 (5.332 to 5.540) | 5.419 (5.319 to 5.525) |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - male. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup Sex - Male With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 99 | 121 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - female. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup Sex - Female With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 32 | 47 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age \<60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup Age <60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 68 | 93 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age ≥60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup Age ≥60y With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment. | 63 | 75 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type of Diabetes - type 1 diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - Type 1 Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 38 | 45 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type 2 and other diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - Type 2 or Other Type of Diabetes With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 93 | 123 |
Primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR \<60mL/min/1.73m\^2). The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - eGFR <60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 17 | 32 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR ≥60mL/min/1.73m\^2. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - eGFR ≥60 mL/Min/1.73m^2 With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 114 | 136 |
Primary outcome in prespecified subgroup according to the baseline characteristic: HbA1c at Screening \<70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - HbA1c <70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 63 | 81 |
Primary outcome in prespecified subgroup according to the baseline characteristic-HbA1c at Screening - ≥70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - HbA1c ≥70 mmol/Mol With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 57 | 79 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic - HbA1c at Screening - Unknown. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup - HbA1c Unknown With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment | 11 | 8 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing of primary outcome - Within first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, Within 1 Year of Randomization | 45 | 63 |
Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing - After first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants in Subgroup With Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment, After 1 Year From Randomization | 86 | 105 |
Based on collection of biochemical data. Urine albumin: creatinine ratio (UACR) results. Urine was collected for measurement of UACR at LENS screening visits wherever possible (baseline results). Post randomization UACR results came from measurements conducted part of routine care. Post randomisation results for a participant were averaged for each participant. Separate values for participants assigned fenofibrate and placebo are reported as geometric mean (95% confidence intervals) and the difference between arms is reported as a percentage difference (95% confidence intervals)
| mg/g | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Percentage Change in Urine Albumin:Creatinine Ratio | 13.6 (12.1 to 15.3) | 15.5 (13.8 to 17.5) |
This outcome is a composite of myocardial infarction, stroke, coronary artery revascularisation and peripheral artery revascularisation.
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With Occurrence of Major Cardiovascular Events (Myocardial Infarction, Stroke, Coronary or Peripheral Revascularisation) | 45 | 43 |
Composite of any non-traumatic lower limb amputation (defined as minor amputation \[distal to the ankle\] or major amputation \[through or proximal to the ankle\]).
| Participants | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Number of Participants With Occurrence of Non-traumatic Lower Limb Amputations | 4 | 11 |
Collected over 4 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fenofibrate 145 mg | 35/576 (6.1%) | 208/576 (36.1%) | 17/576 (3%) |
| Placebo Oral Tablet | 38/575 (6.6%) | 204/575 (35.5%) | 21/575 (3.7%) |
| Event | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Surgical and medical proceduresSurgical and medical procedures | 50/576 | 52/575 |
| Infections and infestationsInfections and infestations | 49/576 | 50/575 |
| Cardiac disordersCardiac disorders | 37/576 | 36/575 |
| Nervous system disordersNervous system disorders | 33/576 | 27/575 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps)Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 29/576 | 23/575 |
| Injury, poisoning and procedural complicationsInjury, poisoning and procedural complications | 23/576 | 28/575 |
| Gastrointestinal disordersGastrointestinal disorders | 21/576 | 27/575 |
| Metabolism and nutrition disordersMetabolism and nutrition disorders | 16/576 | 21/575 |
| Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 19/576 | 14/575 |
| General disorders and administration site conditionsGeneral disorders | 12/576 | 16/575 |
| Event | Fenofibrate 145 mg | Placebo Oral Tablet |
|---|---|---|
| Gastrointestinal disordersGastrointestinal disorders | 6/576 | 5/575 |
| Nervous system disordersNervous system disorders | 4/576 | 3/575 |
| InvestigationsInvestigations | 1/576 | 3/575 |
| Skin and subcutaneous tissue disordersSkin and subcutaneous tissue disorders | 0/576 | 3/575 |
| Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders | 3/576 | 2/575 |
| Eye disordersEye disorders | 2/576 | 2/575 |
| Hepatobiliary disordersHepatobiliary disorders | 0/576 | 1/575 |
| Pregnancy, puerperium and perinatal conditionsPregnancy, puerperium and perinatal conditions | 0/576 | 1/575 |
| Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 1/576 | 1/575 |
| Age, Continuous(years) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| Mean | 60.8 ± 12.4 | 60.6 ± 12.3 | 60.7 ± 12.3 |
| Sex: Female, Male(Participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| Female | 156 | 156 | 312 |
| Male | 420 | 419 | 839 |
| Race/Ethnicity, Customized(Participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 4 | 6 | 10 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 2 | 3 |
| White | 567 | 558 | 1125 |
| Other | 4 | 9 | 13 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| United Kingdom | 576 | 575 | 1151 |
| Type of diabetes mellitus(Participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| Type 1 | 154 | 151 | 305 |
| Type 2 | 421 | 423 | 844 |
| Other | 1 | 1 | 2 |
| Duration of diabetes(years) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| Mean | 18.3 ± 10.5 | 17.7 ± 10.0 | 18 ± 10.25 |
| Retinopathy grading (worse grade)(Participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| No retinopathy (R0) | 5 | 4 | 9 |
| Mild background retinopathy (R1) | 562 | 564 | 1126 |
| Observable background retinopathy (R2) | 9 | 7 | 16 |
| Maculopathy grading (worse eye)(Participants) | Fenofibrate 145 mg | Placebo Oral Tablet | Total |
|---|---|---|---|
| No maculopathy (M0) | 517 | 515 | 1032 |
| Observable diabetic maculopathy (M1) | 59 | 60 | 119 |
14 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Data generated by LENS will be available on application to bona fide academic researchers in accordance with the Data Access Policy for the Nuffield Department of Population Health, University of Oxford. Such approvals will also need to be consistent with the informed consent provided by participants. Any sharing of data derived from NHS Scotland data will need to comply with the approvals of the trial.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Access criteria: Applications will be considered in accordance with Data Access Policy for the Nuffield Department of Population Health, University of Oxford.
Data sharing details ↗ · www.ndph.ox.ac.uk
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Studies of the drug tested here: Fenofibrate