A RANDOMIZED CONTROLLED TRIAL OF ALLOPURINOL FOR CVD IN CKD: STUDY POPULATION CHARACTERISTICS

Hyperuricemia is associated with adverse cardiovascular disease (CVD) outcomes in chronic kidney disease (CKD). Despite short-term favourable modulation of CV function by hypouricemic agents in CKD, evidence on long-term benefits are lacking. Recent clinical trials have not shown benefit of allopurinol in delaying progression of CKD. However, these trials were not specifically designed to assess impact on CVD outcomes in CKD. In the present study, we are testing the hypothesis that compared to placebo, allopurinol would significantly reduce the risk of major adverse cardiovascular events (MACE) in patients with CKD. The secondary objectives include impact of allopurinol on composite of all-cause death and MACE, need for renal replacement therapy (RRT) and composite of 50% decline in eGFR and need of RRT.

The study is a multi-centric, double-blind, placebo-controlled, randomized controlled trial. Eligible participants include stable adult patients with CKD having estimated glomerular filtration rate (eGFR) between 10 to 45 ml/min/1.73m² and serum uric acid levels ≥6 mg/dl. Exclusion criteria include patients with gout, hypersensitivity to allopurinol, or poor functional status. Enrolled participants are randomly assigned to receive either allopurinol at a dose of 100 mg/day or a matching placebo. The proposed follow up of study participants is 36 months. The trial has been prospectively registered at the clinical trials registry of India (CTRI/2020/05/025044). The study will enrol approximately 5000 participants.

In this ongoing study, 649 participants have been enrolled in 8 centres across India over last 2 years,. The average age of participants is 51.5±12.7 years, with two-thirds being male. The clinical cause of CKD is not known in 39% of the study population. Diabetic kidney disease and chronic interstitial nephritis are other leading causes in 18% and 15% participants, respectively (table 1). The median duration of CKD in the study population is 37.6 (6, 48) months. History of hypertension, smoking, diabetes mellitus, renal stone disease and coronary artery disease has been documented in 82%, 19%, 29%, 20% and 7% of participants, respectively. The average serum creatinine and uric acid levels at enrolment are 2.75 ± 0.97 mg/dl and 8.21 ± 1.55 mg/dl, respectively (table 2). Till now, suspected drug related hypersensitivity or adverse event, any new hospitalization, progression to dialysis or having received transplant, new diagnosis of gout, death and any new MACE event have been recorded in 19, 25, 13, 9, 8 and 5 participants, respectively.

Table 1: : Baseline clinical characteristics of study population who have been enrolled (n=649)

Table 2: Demographic and baseline biochemical characteristics of study population

This study represents the largest clinical trial that is investigating the impact of allopurinol on CVD outcomes in patients with CKD and hyperuricemia.

[The work is supported by grant from India Alliance (Department of Biotechnology, Government of India and Wellcome Trust, UK) to VK (IA/CPHI/18/1/503954)].