W Frank Peacock1, Zubaid Rafique1, Konstantin Vishnevskiy2, Edward Michelson3, Elena Vishneva4, Tatiana Zvereva5, Rajaa Nahra6, Dao Li7, Joseph Miller8. 1. From the, Baylor College of Medicine, Ben Taub General Hospital, Houston, TX. 2. the, First Pavlov State, Medical University of St. Petersburg, St. Petersburg, Russia. 3. the, Department of Emergency Medicine, Texas Tech University Health Sciences Center, El Paso, TX. 4. the, Scientific Centre of Children's Health, Russian Academy of Medical Science, Moscow, Russia. 5. the, Scientific Research Institution for Complex Issues of Cardiovascular Disease, Kemerovo Medical University, Kemerovo, Russia. 6. AstraZeneca, Gaithersburg, MD. 7. AstraZeneca, Gothenburg, Sweden. 8. and the, Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI.
Abstract
OBJECTIVES:Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS: This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS: Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS: This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.
RCT Entities:
OBJECTIVES:Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED). METHODS: This exploratory, phase II, multicenter, randomized, double-blind, placebo-controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium (sK+ ) from baseline until 4 hours after start of dosing. RESULTS: Overall, 70 patients were randomized (SZC n = 33, placebo n = 37), of whom 50.0% were male. Their mean (± standard deviation [±SD]) age was 59.0 (±13.8) years and mean initial sK+ was similar between groups (SZC 6.4 mmol/L, placebo 6.5 mmol/L). The least squares mean (±SD) sK+ change from baseline to 4 hours was -0.41 (±0.11) mmol/L and -0.27 (±0.10) mmol/L with SZC and placebo, respectively (difference = -0.13 mmol/L, 95% confidence interval [CI] = -0.44 to 0.17). A greater reduction in mean (±SD) sK+ from baseline occurred with SZC compared with placebo at 2 hours: -0.72 (±0.12) versus -0.36 (±0.11) mmol/L (LSM difference = -0.35 mmol/L, 95% CI = -0.68 to -0.02), respectively. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo (15.6% vs. 30.6%, respectively; odds ratio = 0.40, 95% CI = 0.09 to 1.77). Comparable proportions of patients experienced adverse events in both treatment groups at 0 to 24 hours. CONCLUSIONS: This pilot study suggested that SZC with insulin and glucose may provide an incremental benefit in the emergency treatment of hyperkalemia over insulin and glucose alone.
Authors: Mitra K Nadim; Lui G Forni; Ravindra L Mehta; Michael J Connor; Kathleen D Liu; Marlies Ostermann; Thomas Rimmelé; Alexander Zarbock; Samira Bell; Azra Bihorac; Vincenzo Cantaluppi; Eric Hoste; Faeq Husain-Syed; Michael J Germain; Stuart L Goldstein; Shruti Gupta; Michael Joannidis; Kianoush Kashani; Jay L Koyner; Matthieu Legrand; Nuttha Lumlertgul; Sumit Mohan; Neesh Pannu; Zhiyong Peng; Xose L Perez-Fernandez; Peter Pickkers; John Prowle; Thiago Reis; Nattachai Srisawat; Ashita Tolwani; Anitha Vijayan; Gianluca Villa; Li Yang; Claudio Ronco; John A Kellum Journal: Nat Rev Nephrol Date: 2020-10-15 Impact factor: 28.314
Authors: Pietro Scicchitano; Massimo Iacoviello; Francesco Massari; Micaela De Palo; Pasquale Caldarola; Antonia Mannarini; Andrea Passantino; Marco Matteo Ciccone; Michele Magnesa Journal: Biomedicines Date: 2022-07-16
Authors: Carsten Lott; Anatolij Truhlář; Anette Alfonzo; Alessandro Barelli; Violeta González-Salvado; Jochen Hinkelbein; Jerry P Nolan; Peter Paal; Gavin D Perkins; Karl-Christian Thies; Joyce Yeung; David A Zideman; Jasmeet Soar Journal: Notf Rett Med Date: 2021-06-10 Impact factor: 0.826
Authors: José Luis Gorriz; Luis D'Marco; Anna Pastor-González; Pablo Molina; Miguel Gonzalez-Rico; María Jesús Puchades; Irina Sanchis; Verónica Escudero; Nuria Estañ; Rafael de la Espriella; Eduardo Nuñez; Luis Pallardó; Julio Núñez Journal: Nephrol Dial Transplant Date: 2022-02-25 Impact factor: 5.992