Mineralocorticoid Receptor Antagonists for Hypertension Management in Advanced Chronic Kidney Disease: BLOCK-CKD Trial


Spironolactone, a steroidal mineralocorticoid receptor antagonist, is recommended as add-on therapy for treatment-resistant/uncontrolled hypertension. However, caution is advised in patients with advanced chronic kidney disease (CKD) due to an increased risk for hyperkalemia. KBP-5074 is a nonsteroidal mineralocorticoid receptor antagonist under investigation for the treatment of treatment-resistant and uncontrolled hypertension in patients with moderate-to-severe CKD. BLOCK-CKD is a phase 2, international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of KBP-5074, on top of current therapy, in patients with stage 3B/4 CKD (estimated glomerular filtration rate ≥15 and ≤44 mL/[min·1.73 m2]) and resistant hypertension (trough cuff seated systolic blood pressure ≥140 mm Hg, despite treatment with maximally tolerated doses of 2 or more antihypertensive medicines with complementary mechanisms). Patients (n=240) will be randomized 1:1:1 to once-daily treatment with KBP-5074 0.25 mg, KBP-5074 0.5 mg, or placebo, stratified by estimated glomerular filtration rate (≥30 versus <30 mL/[min·1.73 m2]) and systolic blood pressure (≥160 versus <160 mm Hg). Approximately 30% of enrolled patients should have an estimated glomerular filtration rate of 15 to 29 mL/(min·1.73 m2). The primary efficacy analysis is the change in trough cuff seated systolic blood pressure from baseline to day 84 for the KBP-5074 doses compared with placebo. Changes in urinary albumin-creatinine ratio will be assessed along with changes in serum potassium/incidence of hyperkalemia and changes in estimated glomerular filtration rate and serum creatinine. BLOCK-CKD will determine whether the addition of KBP-5074 will effectively lower blood pressure without an increased risk of hyperkalemia in patients who are not candidates for steroidal mineralocorticoid receptor antagonists due to advanced CKD.

Authors: George Bakris, Y Fred Yang, Bertram Pitt
Keywords: albuminuria, creatinine, drug resistance, glomerular filtration rate, chronic renal insufficiency, KBP-5074
DOI Number: 10.1161/HYPERTENSIONAHA.120.15199      Publication Year: 2020

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