Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): design of a multicentre, randomised, double-blind, placebo-controlled, parallel-group study

Abstract

Introduction: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K⁺) (including albuterol, glucose and insulin) may cause hypoglycaemia. We outline the design and rationale of the Patiromer Utility as an Adjunct Treatment in Patients Needing Urgent Hyperkalaemia Management (PLATINUM) study, which will be the largest ED randomised controlled hyperkalaemia trial ever performed, enabling assessment of a standardised approach to hyperkalaemia management, as well as establishing a new evaluation parameter (net clinical benefit) for acute hyperkalaemia treatment investigations.

Methods and analysis: PLATINUM is a Phase 4, multicentre, randomised, double-blind, placebo-controlled study in participants who present to the ED at approximately 30 US sites. Approximately 300 adult participants with hyperkalaemia (K⁺ ≥5.8 mEq/L) will be enrolled. Participants will be randomised 1:1 to receive glucose (25 g intravenously <15 min before insulin), insulin (5 units intravenous bolus) and aerosolised albuterol (10 mg over 30 min), followed by a single oral dose of either 25.2 g patiromer or placebo, with a second dose of patiromer (8.4 g) or placebo after 24 hours. The primary endpoint is net clinical benefit, defined as the mean change in the number of additional interventions less the mean change in serum K⁺, at hour 6. Secondary endpoints are net clinical benefit at hour 4, proportion of participants without additional K⁺-related medical interventions, number of additional K⁺-related interventions and proportion of participants with sustained K⁺ reduction (K⁺ ≤5.5 mEq/L). Safety endpoints are the incidence of adverse events, and severity of changes in serum K⁺ and magnesium.

Ethics and dissemination: A central Institutional Review Board (IRB) and Ethics Committee provided protocol approval (#20201569), with subsequent approval by local IRBs at each site, and participants will provide written consent. Primary results will be published in peer-reviewed manuscripts promptly following study completion.

Trial registration number: NCT04443608.

Keywords: accident & emergency medicine; clinical trials; heart failure; hypertension.

Figure 1

PLATINUM study design. *Local laboratory or point-of-care testing may be used to confirm eligibility for the study. K⁺ testing can be repeated at the discretion of the investigator at any time during the treatment period but is required at hour 4. ED, emergency department; EoED, end of emergency department stay (defined as discharge from the ED or initiation of dialysis); HD, haemodialysis; SCT, standard combination therapy (defined as 5 U intravenous insulin, 25 g intravenous glucose and 10 mg aerosolised albuterol) and K⁺-related medical intervention (defined as additional administration of insulin, glucose or albuterol (or their combination) at any dose, or any other K⁺-lowering medication can be initiated and repeated at the discretion of the investigator at any time); however, SCT is recommended.

Figure 2

Proposed study centre locations. Study centres actively enrolling participants are shown on map. (1) Stanford University School of Medicine, California; (2) Henry JN Taub Hospital/Baylor College of Medicine, Texas; (3) Hennepin County Medical Center, University of Minnesota, Minnesota; (4) Stony Brook University Hospital, Stony Brook, New York; (5) Yale University, Connecticut; (6) Henry Ford Hospital, Michigan; (7) University of Cincinnati, Ohio; (8) Wake Forest University, North Carolina; (9) The Ohio State University Wexner Medical Center, Ohio; (10) Baystate Health, Massachusetts; (11) Washington University in St. Louis, Missouri; (12) UT Memorial Hermann Hospital, Texas Medical Center, Texas; (13) Mount Sinai, Icahn School of Medicine, New York; (14) Cristiana Care, Wilmington, Delaware; (15) University of Kansas Medical Center, Kansas; (16) Meritus Medical Center, Maryland; (17) George Washington University, Washington DC.

Figure 3

Primary endpoint: net clinical benefit. ‡Number of additional potassium (K⁺)-lowering interventions after initial treatment. ∆K will be determined from laboratory potassium (K⁺) values.