None listed
Conditions
Brief summary
Chronic kidney disease (CKD), defined as an eGFR <60 ml/min/1.73 m2 and/or the presence of kidney damage (albuminuria or proteinuria) for at least 3 months, is a major public health problem affecting approximately 1.6 million Australian adults. Of these affected individuals, approximately 930,000 have stages 3-4 CKD (eGFR 15-60 mL/min/1.73 m2). CKD patients have a greatly increased risk of adverse renal and cardiovascular (CV) outcomes, even in its early stages. CKD patients are at increased risk of progression to end-stage kidney disease (ESKD). The incidence of ESKD is increasing in Australia by 6% per annum. Apart from an increased risk of ESKD, the presence of CKD is one of the most potent known risk factors for cardiovascular disease (CVD), such that individuals with CKD are more likely to die, mostly from CVD, than survive to the point of needing dialysis or kidney transplantation. A reduction in eGFR <60 ml/min/1.73 m2 is associated with increased risks of all-cause and CV mortality. The CKD-FIX trial aims to critically examine the efficacy and safety of allopurinol as an agent to slow the progression of chronic kidney disease (CKD).
Interventions
Participants will be randomised to either allopurinol or matching placebo after informed consent. The starting dose will be 1 tablet daily of allopurinol (100mg) for 4 weeks. If tolerated, the dose will be increased to 2 tablets daily for another 4 weeks. If tolerated the dose will be further increased to 3 tablets daily thereafter. The maximally tolerated dose (1 or 2 or 3 tablets daily will be continued during the remaining follow up period (total follow up of 104 weeks).
Sponsors
Australasian Kidney Trials Network (University of Qld)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult (age greater than or equal to 18 years) 2. CKD stage 3 or 4 (eGFR 15 to 59 mL/min/1.73 m2) 3. Random urine albumin to creatinine ratio greater or equal to 30mg/mmol OR Evidence of progression of CKD (decrease in eGFR greater than or equal to 3.0 mL/min/1.73 m2 during the preceding 12 months, calculated as the difference between the first and last tests, based on minimum of 3 blood tests with each test done at least 4 weeks apart). For diagnosis of CKD and determination of eGFR decline, eGFR estimates by either MDRD or CKD-EPI equation can be used according to the local practice.
Exclusion criteria
1. Past history of clinically established gout, according to the 2015 ACR/EULAR gout classification criteria, 2. History of hypersensitivity to allopurinol, 3. Kidney transplant recipients, 4. Concurrent treatment with azathioprine, 6-mercaptopurine, theophylline, cyclophosphamide, cyclosporine, probenecid, phenytoin, or chlorpropamide, 5. Indication for allopurinol, including history of tophus or tophi on clinical examination or imaging study, uric acid nephropathy, uric acid nephrolithiasis or urolithiasis, 6. Current non-skin cancer malignancy, 7. Unresolved acute kidney injury in last 3 months, 8. Current pregnancy, breast feeding, 9. Any uncontrolled psychological illness or condition which interferes with their ability to understand or comply with the requirements of the study, 10. Elective or imminent initiation of maintenance dialysis or kidney transplantation expected in the next 6 months.
Outcome results
None listed