| Participants |
Where the participants were recruited: Hong Kong, New Zealand, and Australia
Single centre or multicentre: multicentre
Setting: clinic
Number of recruiting centres: 21
Baseline Characteristics
fenofibrate
Number of participants: Men, n (%): Age, years, mean (SD): Caucasian, n (%): Non‐Caucasian, n (%): T1D, n (%): T2D, n (%): Overt retinopathy, n (%): DR status none, n (%): DR status mild, n (%): DR status moderate NPDR, n (%): DR status severe NPDR, n (%): DR status PDR, n (%): T‐chol (mmol/L), mean (SD): LDL‐C (mmol/L), mean (SD): HDL‐C (mmol/L), mean (SD): TG (mmol/L), median (IQR): HbA1c (%), median (IQR):
placebo
Number of participants: Men, n (%): Age, years, mean (SD): Caucasian, n (%): Non‐Caucasian, n (%): T1D, n (%): T2D, n (%): Overt retinopathy, n (%): DR status none, n (%): DR status mild, n (%): DR status moderate NPDR, n (%): DR status severe NPDR, n (%): DR status PDR, n (%): T‐chol (mmol/L), mean (SD): LDL‐C (mmol/L), mean (SD): HDL‐C (mmol/L), mean (SD): TG (mmol/L), median (IQR): HbA1c (%), median (IQR):
Equivalence of baseline characteristics:
Inclusion criteria:
Men or non‐pregnant women (on acceptable contraception) with T1D according to standard criteria; T1D defined as either (a.) T1D diagnosed below 40 years of age and insulin therapy commencing within one year of T1D diagnosis, or (b.) T1D diagnosed at or after 40 years of age along with: i) documented history of ketoacidosis, and/or ii) documented history of very low or undetectable C‐peptide (fasting < 200 nmol/L or 0.2 pmol/L), and/or iii) documented history of T1D related autoantibody/ies (anti‐GAD, anti‐A2, anti‐ZnT8) Age 18 years or over eGFR must exceed 30 mL/min/1.73 m² Must have at least one eligible eye with NPDR (ETDRS scale 35 to 53 inclusive) confirmed by current retinal photography within the last 3 months (irrespective of prior laser therapy); any eye having undergone prior pan‐retinal laser therapy is not eligible, but prior focal, macular or grid laser does not exclude that eye from eligibility All types of insulin therapy, with no restriction by level of HbA1c Willing and able to comply with all study requirements, including treatment, assessment and clinic visit attendances Able to personally read and understand the Participant information and consent form and provide written, signed, and dated informed consent to participate in study
Exclusion criteria:
Definite indication for, or contraindications to fibrate treatment (other lipid drugs, e.g. statins, ezetimibe, fish oils allowed) Need for bilateral intra‐ocular treatment or laser photocoagulation therapy within the next 3 months (this exclusion only applies to retinal laser photocoagulation treatment onto the posterior pole, i.e. laser correction of corneas for short‐sightedness is not an exclusion criterion) Prior bilateral PRP treatment for DR Prior bilateral intra‐ocular injection(s) within the last 6 months Bilateral cataract surgery within the last 6 months Planned bilateral cataract surgery within the next 12 months History of any other non‐diabetic eye disease that is, or is likely to affect bilateral vision History of photosensitive skin rash or myositis Abnormal thyroid function (untreated) Liver function tests exceeding 3 x ULN Persistent elevated unexplained blood CK level above normal range Documented fasting triglyceride levels > 6.5 mmol/L History of pancreatitis, deep‐vein thrombosis, or pulmonary embolism Use of investigational drugs in the prior 8 weeks Any unstable condition in last 3 months, including active sepsis, diabetic ketoacidosis MI, unstable angina, stroke, or heart failure within last 6 months Diagnosed cancer with ongoing treatment or prognosis anticipated at < 5 years Any obstacle to regular follow‐up, including scheduled clinic attendances Prior or planned organ transplantation (including islet cell) with subsequent continued immunosuppression therapy
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| Outcomes |
Primary outcome:
Occurrence of clinically significant retinopathy progression, defined as comprising 2‐step progression of ETDRS scale (to at least moderately severe grade), occurrence of clinically significant DMO, need for laser treatment, need for intraocular anti‐VEGF or corticosteroid therapy or vitrectomy adjudicated to be for retinopathy
Secondary outcomes:
Individual components of the primary end point Visual Acuity Retinal vessel calibre and geometry Macular volume and thickness by OCT Urine albumin:creatinine ratio eGFR (measured 8 weeks after treatment withdrawal) Measures of peripheral neuropathy (symptoms, monofilament testing, vibration, and temperature sensation) Autonomic neuropathy: QTc and RR intervals on yearly ECGs Total cardiovascular events, including MI (including silent MI by ECGs), stroke, sudden cardiac death, hospitalisation for acute coronary syndrome, or any revascularization requirement Frequency of foot ulcer and non‐traumatic amputation Lipid and lipoprotein levels Biomarkers and molecular markers Quality of life questionnaire
Outcomes reported in manuscript:
Adverse effects:
Unit of measure:
Planned length of follow up: 36 months
Actual length of follow up:
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