The CKD-FIX Trial: Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase

INTERVENTION: 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). CONDITION: Chronic Kidney Disease stages 3 and 4 PRIMARY OUTCOME: Change in estimated glomerular filtration rate (eGFR) at 104 weeks. The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation will be used to estimate eGFR. SECONDARY OUTCOME: Adverse events (especially adverse drug reactions such as severe cutaneous adverse reactions‐ Erythema Multiforme, Stevens‐Johnson Syndrome, Toxic Epidermal Necrolysis, minor skin rash, hypersensitivity syndrome, aplastic anaemia, thrombocytopenia) all‐cause death all‐cause hospitalisation ‐ assessed by the collection of data from serious adverse events, Medical Benefits Scheme and Pharmaceutical Benefits Scheme, and the Health Costs Questionnaire blood pressure The average of three blood pressure readings is calculated by adding the three systolic or diastolic readings together and dividing by 3 change in Cystatin C‐based eGFR composite of reduction in GFR >30% from baseline, End Stage Kidney Disease, and death from any cause. Cost‐effectiveness and economic analyses Degree of proteinuria, measured via a 24 hour urine collection fatal or non‐fatal cardiovascular events during course of follow‐up period of 104 weeks progression to End Stage Kidney Disease requiring dialysis or kidney transplantation; (i.e. if the participant commences dialysis or requires a transplant in the trial follow‐up period of 104 weeks). quality of life, as assessed using the Short‐Form 36 health survey (self‐report) reduction in GFR >30% from baseline Serum uric acid concentration 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 wither MDRD or CKD‐EPI equation can be used according to the local practice.