Effect of Sodium Hydrogen Carbonate on Major Adverse Kidney Events in Critically Ill Patients with Metabolic Acidosis and Acute Kidney Injury

The primary objective of this study is to evaluate the effect of sodium hydrogen carbonate on major adverse kidney events at day 90 in patients presenting with metabolic acidosis and acute kidney injury during critical illness. Secondary objectives include the assessment of:

• All-cause mortality at 90 days;
• Persistent renal dysfunction;
• Requirement for kidney replacement therapy (KRT) during the first 90 days post-randomization and KRT dependence at day 90;
• Number of KRT-free days up to day 90.

The sponsor did not provide information regarding the total number of participants. The study population consists of adults, including both male and female individuals, who are categorized as vulnerable. Participants are critically ill patients requiring management within an intensive care unit or intermediate care unit. Inclusion requires a diagnosis of metabolic acidosis, characterized by an arterial pH ≤7.25, PaCO2 < 49 mmHg, standard bicarbonate ≤20 mmol/L, and a standard base excess < -2. Additionally, subjects must present with acute kidney injury classified as stage 2 or 3 according to the KDIGO classification.

This Phase IV clinical trial is designed to evaluate the clinical effectiveness of sodium hydrogen carbonate compared to various electrolyte comparator solutions in patients experiencing metabolic acidosis and acute kidney injury. The research methodology focuses on investigating the impact of the test substance on major adverse kidney events at day 90. Participants must be adults aged 18 years or older who are receiving care in an intensive care unit or intermediate care unit. Inclusion criteria require a diagnosis of stage 2 or 3 acute kidney injury according to the KDIGO classification, alongside specific arterial pH, PaCO2, bicarbonate, and base excess levels. The primary endpoint is defined as the occurrence of mortality, any kidney replacement therapy, or persistent renal dysfunction at 90 days post-randomization. Secondary endpoints include all-cause mortality, creatinine level elevation, and kidney replacement therapy-free days. The study involves a screening process to confirm eligibility followed by randomization and treatment. The follow-up period extends to 90 days to assess renal outcomes and mortality. The total duration of the study is estimated from March 2026 to June 2026.

The experimental treatment consists of sodium hydrogen carbonate administered via intravenous perfusion at a dose of 2400 ml.

The comparator treatments include several electrolyte solutions. Jonosteril Infusionslösung is a solution for infusion containing sodium chloride, calcium acetate, magnesium acetate tetrahydrate, potassium acetate, and sodium acetate trihydrate, administered via intravenous perfusion at a dose of 2400 ml. Elektrolyt-Infusionslösung 153 is an intravenous perfusion solution containing magnesium chloride hexahydrate, potassium chloride, sodium chloride, calcium chloride dihydrate, and sodium acetate trihydrate at a dose of 2400 ml. Sterofundin ISO Infusionslösung is a solution for infusion containing magnesium chloride hexahydrate, potassium chloride, sodium chloride, calcium chloride dihydrate, malic acid, and sodium acetate trihydrate, administered via intravenous perfusion at a dose of 2400 ml. Ringer-Infusionslösung B. Braun is a solution for infusion containing potassium chloride, sodium chloride, and calcium chloride dihydrate, administered via intravenous perfusion at a dose of 2400 ml.

The primary efficacy endpoint is the occurrence of major adverse kidney events (MAKE90) at day 90. This binary endpoint is defined as mortality, the initiation of any kidney replacement therapy (KRT) within 90 days after randomization, or persistent renal dysfunction, characterized by a creatinine value at day 90 that is greater than or equal to 200% of the baseline value.

Secondary efficacy parameters include:

• All-cause mortality at 90 days.
• Elevation of creatinine levels to ≥200% of the baseline value at day 90, measured between day 80 and 120 after randomization.
• Receipt of any form of KRT within the 90-day period following randomization.
• KRT-dependence at day 90 after randomization.
• KRT-free days, calculated as the difference between the number of days alive and the number of days receiving any form of KRT between randomization and day 90.