PERL: A multicenter clinical trial of allopurinol to prevent GFR loss in T1D

To determine whether lowering serum uric acid by means of allopurinol early in the course of kidney disease may be effective in preventing or slowing the decline of renal function in T1D patients. This is a 9-week run-in period, during which RAS inhibition with ramipril 10 mg will be introduced and BP normalized, if elevated above 130/80 mmHg, followed by a 3-year treatment period. After the run-in period, eligible subjects will be randomized in a 1 to 1 ratio to receive oral allopurinol or placebo. Allopurinol dose will be titrated from 100 to 400 mg per day, subdivided in two doses, with a goal of decreasing serum UA values to 2.5-4.5 mg/dl, with a reduction of at least 30% from baseline levels. Data will be analyzed according to an intention-to-treat approach. Differences between treatment arms in the primary outcome will be tested for significance by means of a linear model with correlated errors. Intervention effects on other secondary outcomes will be tested by mixed-effect models (GFR time trajectory), ANCOVA (AER), and survival analysis (time to serum creatinine doubling/ESRD and CVD events).