The purpose of this study is to evaluate the potential benefits of 145 mg of daily fenofibrate in adults with type 1 diabetes mellitus and pre-existing non-proliferative diabetic retinopathy.
Diabetes is the most common cause of adult onset blindness. Irreversible vision loss is a most feared complication of diabetes. Fenofibrate is a blood fat lowering drug available in Australia and has been shown to reduce eye damage in people with Type 2 diabetes by 35-40%, and to prevent eye damage in Type 1 diabetic animal models. This study will evaluate the potential benefits of oral Fenofibrate 145mg once daily for average 36 months in 450 adults with Type 1 diabetes mellitus who are at high risk of eye damage.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
412
145 mg tablet of fenofibrate administered once daily for 36 months.
Insert lactose tablet matching active tablet administered once daily for 36 months.
Canberra Hospital
Garran, Australian Capital Territory, Australia
Occurrence of clinical significant retinopathy progression.
Comprising 2-step progression of ETDRS score (to at least moderately severe grade), clinically significant macular oedema, need for laser surgery, need for intraocular anti-VEGF or corticosteroid therapy or vitrectomy, adjudicated to be for diabetic retinopathy (DR)
Time frame: As reported throughout the study and/or annual eye assessment post-randomisation
The individual components of the primary endpoint
Clinically significant retinopathy progression, 2-step progression of ETDRS score
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Occurrence of clinically significant macula oedema (CSME).
Occurrence of clinically significant macula oedema (CSME) per standard ophthalmological assessment or laser therapy.
Time frame: As reported throughout the study
Need for laser surgery for DR
Need for laser surgery for DR
Time frame: As reported throughout the study
Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy
Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy for DR
Time frame: As reported throughout the study
Visual acuity.
Visual acuity using ETDRS/LogMar or Snellen Chart
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
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Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Concord Repatriation General Hospital
Concord, New South Wales, Australia
Garvan Institute of Medical Research
Darlinghurst, New South Wales, Australia
Retina Associates - South West Retina
Liverpool, New South Wales, Australia
Hunter Diabetes Centre
Merewether, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
Cairns Hospital
Cairns, Queensland, Australia
Mater Adult Hospital
South Brisbane, Queensland, Australia
...and 14 more locations
Macular volume and thickness
Macular volume and thickness by Optical Coherence Tomography (OCT)
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Albuminuria.
Albuminuria measured as urinary albumin:creatinine ratio.
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation, the end of study visit (which is on average 36 months post-randomisation) and wash-out visit.
Estimated glomerular filtration rate.
Estimated glomerular filtration rate using Modification of Diet in Renal Disease (MDRD) formula.
Time frame: At study completion and washout visit
Peripheral neuropathy status
Peripheral neuropathy status assessed by temperature \& vibration sensation and monofilament test.
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Autonomic neuropathy.
Autonomic neuropathy (QTc and R-R intervals) on annual ECGs.
Time frame: At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).
Total cardiovascular events.
Total cardiovascular events including myocardial infarction, stroke, sudden cardiac death, hospitalisation for acute coronary syndrome or any revascularisation events.
Time frame: As reported throughout the study.
Frequency of foot ulcer and non-traumatic amputation.
Foot ulcer and/or non-traumatic amputation are reported by site during the study.
Time frame: As reported throughout the study