Kidney360 · 2024
Sodium Zirconium Cyclosilicate in CKD, Hyperkalemia, and Metabolic Acidosis: NEUTRALIZE Randomized Study.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Ash Stephen R, Batlle Daniel, Kendrick Jessica, Oluwatosin Yemisi, Kooienga Laura, Eudicone James M, Sundin Anna-Karin, Guerrieri Emily, Fried Linda F
Аннотация
KEY POINTS: Sodium zirconium cyclosilicate effectively lowers serum potassium and maintains normokalemia in patients with CKD with concomitant hyperkalemia and metabolic acidosis. Despite high screen failure and small sample size, a nominally significant increase in sHCO3– was seen for sodium zirconium cyclosilicate versus placebo. Further studies on the basis of an appropriate cohort size may help validate the trend observed in sHCO3– levels, supporting these clinically relevant findings.
BACKGROUND: Metabolic acidosis and hyperkalemia are common in CKD. A potential dual effect of sodium zirconium cyclosilicate (SZC), a selective binder of potassium in the gastrointestinal tract, on serum potassium (sK+) and serum bicarbonate (sHCO3−) was evaluated in patients with hyperkalemia and metabolic acidosis associated with CKD.
METHODS: In the NEUTRALIZE study (NCT04727528), non-dialysis patients with stage 3–5 CKD, hyperkalemia (sK+>5.0 to ≤5.9 mmol/L), and metabolic acidosis (sHCO3− 16–20 mmol/L) received open-label SZC 10 g three times daily for ≤48 hours. Patients achieving normokalemia (sK+ 3.5–5.0 mmol/L) were randomized 1:1 to SZC 10 g or placebo daily for 4 weeks. The primary end point was patients (%) maintaining normokalemia at the end of treatment (EOT) without rescue. Secondary end points included mean change in sHCO3− at EOT (day 29) and patients (%) with normokalemia with a ≥3-mmol/L increase in sHCO3− without rescue.
RESULTS: Of 229 patients screened, 37 were randomized (SZC, n=17; placebo, n=20). High screen failure led to early study termination. At EOT, 88.2% (SZC) versus 20.0% (placebo) of patients maintained normokalemia (odds ratio, 56.2; P = 0.001). Low enrollment rendered secondary end point P values nominal. SZC treatment provided nominally significant increases in sHCO3– versus placebo from day 15 onward. Patients with normokalemia with a ≥3-mmol/L increase in sHCO3− without rescue were 35.3% (SZC) and 5.0% (placebo; P < 0.05). No new safety concerns were reported.
CONCLUSIONS: SZC effectively lowered sK+ and maintained normokalemia, with nominally significant increases in sHCO3– observed for SZC versus placebo.
BACKGROUND: Metabolic acidosis and hyperkalemia are common in CKD. A potential dual effect of sodium zirconium cyclosilicate (SZC), a selective binder of potassium in the gastrointestinal tract, on serum potassium (sK+) and serum bicarbonate (sHCO3−) was evaluated in patients with hyperkalemia and metabolic acidosis associated with CKD.
METHODS: In the NEUTRALIZE study (NCT04727528), non-dialysis patients with stage 3–5 CKD, hyperkalemia (sK+>5.0 to ≤5.9 mmol/L), and metabolic acidosis (sHCO3− 16–20 mmol/L) received open-label SZC 10 g three times daily for ≤48 hours. Patients achieving normokalemia (sK+ 3.5–5.0 mmol/L) were randomized 1:1 to SZC 10 g or placebo daily for 4 weeks. The primary end point was patients (%) maintaining normokalemia at the end of treatment (EOT) without rescue. Secondary end points included mean change in sHCO3− at EOT (day 29) and patients (%) with normokalemia with a ≥3-mmol/L increase in sHCO3− without rescue.
RESULTS: Of 229 patients screened, 37 were randomized (SZC, n=17; placebo, n=20). High screen failure led to early study termination. At EOT, 88.2% (SZC) versus 20.0% (placebo) of patients maintained normokalemia (odds ratio, 56.2; P = 0.001). Low enrollment rendered secondary end point P values nominal. SZC treatment provided nominally significant increases in sHCO3– versus placebo from day 15 onward. Patients with normokalemia with a ≥3-mmol/L increase in sHCO3− without rescue were 35.3% (SZC) and 5.0% (placebo; P < 0.05). No new safety concerns were reported.
CONCLUSIONS: SZC effectively lowered sK+ and maintained normokalemia, with nominally significant increases in sHCO3– observed for SZC versus placebo.