Randomized Embedded Adaptive Platform Trial in South Asian Adults with Biopsy-Proven Primary IgA Nephropathy Comparing Multiple Drugs and Standard Care

What this Trial Is About

Chronic kidney disease (CKD) is a major cause of death worldwide, with a rising impact in South Asia. In this region, one in seven adults has CKD, and IgA nephropathy (IgAN) is the most common primary glomerular disease affecting adults. Studies show South Asians with IgAN experience severe and rapid kidney function decline. Recent trials indicate that steroids' benefits may fade over time, highlighting the need for longer-term treatment options. This trial aims to evaluate commonly available generic drugs alongside standard care to improve kidney outcomes in South Asian adults with biopsy-proven IgAN at high risk of progression. The trial is a multi-center, randomized, single-blind, multi-arm, and multi-stage platform study comparing several drugs added to standard care (SoC) against SoC alone. SoC includes maximal tolerated doses of ACE inhibitors or angiotensin receptor blockers and a steady dose of SGLT2 inhibitors. The drugs studied include low-dose oral prednisolone, gut-directed budesonide, mycophenolate mofetil, hydroxychloroquine, and a non-steroidal mineralocorticoid receptor antagonist, with dosing schedules ranging from two months to 24 months. The trial allows adaptive changes, including adding new treatment arms based on interim analyses. Participants will be adults aged 18 to 65 with biopsy-proven primary IgAN and specific kidney function and proteinuria criteria despite standard treatment. They will undergo regular assessments over 24 months, including kidney function tests (eGFR), proteinuria measurements, medication adherence, and patient-reported outcomes. The primary outcome is the change in the annualized eGFR slope over two years. Secondary outcomes include changes in proteinuria, disease progression markers, adverse events, and quality of life measures. Safety and treatment effects will be closely monitored throughout the study period.

Which of the Commonly Available and Approved Drugs in Addition to Standard of Care Can Significantly Improve the Slope of Estimated Glomerular Filtration Rate at Two Years When Compared to Standard of Care Alone in South-Asian Kidney Biopsy-proven Adult (≥18 Years) Primary IgA Nephropathy?