Design and rationale of Japanese evaluation between formula of azelnidipine and amlodipine add on olmesartan to get antialbuminuric effect study (J-FLAG): Evaluation of the antialbuminuric effects between calcium channel blocker with sympatholytic action in hypertensive patients with diabetes and albuminuria

Purpose: Calcium channel blockers (CCBs) are recommended second-line antihypertensives for renin-angiotensin system (RAS) inhibitor-treated patients with chronic kidney disease (CKD), but they do not always ameliorate the progression of CKD. However, small clinical studies suggest that sympatholytic CCBs may protect against kidney injury. Therefore, a clinical trial was designed to test whether the sympatholytic CCB azelnidipine decreases the urinary albumin levels of CKD patients treated with the angiotensin receptor blocker olmesartan more potently than the widely-used non-sympatholytic CCB amlodipine. Methods: A multi-center, open-labeled, randomized clinical intervention trial was designed to compare the antialbuminuric effect of azelnidipine (8-16 mg/day) and amlodipine (2.5-5 mg/day) in olmesartan-treated hypertensive (blood pressure 130-180/80-110 mmHg) patients with type 2 diabetes (fasting blood sugar ≥ 126 mg/dL or treatment with antidiabetic agents) and albuminuria (urinary albumin/creatinine ratio ≥ 30 mg/g). The primary study endpoint is the change in the urinary albumin/creatinine ratio after 12 months of treatment. Conclusions: The present trial is expected to clarify whether the sympatholytic CCB azelnidipine is a beneficial second-line choice for RAS inhibitor-treated hypertensive patients with CKD, such as diabetic nephropathy.