1) Severe heart failure (ejection fraction < 30%) 2) Severe renal insufficiency (eGFR < 30 mL/min/1.73m2) 3) Severe hemodynamic instability (noradrenalin dose > 0.3 μg/kg/min) 4) Prior enrollment in the trial 5) Pregnancy 6) Allergy to senicapoc 7) Inability to take enteral medication 8) More than 24 hours since ICU admission 9) Limitations of care 10) Anticipated death within 24 hours Severe heart failure will pragmatically be defined solely on the basis of the latest measured or estimated ejection fraction obtained via echocardiography (or other image modalities). If no ejection fraction is available, it will be assumed that the patient does not have severe heart failure. Renal insufficiency will be defined based on the latest estimated glomerular filtration rate (eGFR). If a patient is receiving renal replacement therapy, this will likewise be considered severe renal insufficiency. Hemodynamic instability will be defined based on a need for high-dose continuous vasopressor therapy specifically a noradrenalin dose > 0.3 μg/kg/min. If the patient is receiving other vasopressors instead of or in addition to noradrenalin, a noradrenaline-equivalent dose will be estimated based on prior formulas.39 In fertile women (age < 50 years) a negative urine-hCG or plasma-hCG must be present before enrolment. In order to optimize the chances of patients surviving to 72 hours (the time of the primary outcome), patients with limitations of care (including limitations related to mechanical ventilation and renal replacement therapy but not cardiopulmonary resuscitation) and patients with anticipated death within 24 hours, as judged by the treating clinician, will be excluded.

1) Severe heart failure (ejection fraction < 30%) 2) Severe renal insufficiency (eGFR < 30 mL/min/1.73m2) 3) Severe hemodynamic instability (noradrenalin dose > 0.3 μg/kg/min) 4) Prior enrollment in the trial 5) Pregnancy 6) Allergy to senicapoc 7) Inability to take enteral medication 8) More than 24 hours since ICU admission 9) Limitations of care 10) Anticipated death within 24 hours Severe heart failure will pragmatically be defined solely on the basis of the latest measured or estimated ejection fraction obtained via echocardiography (or other image modalities). If no ejection fraction is available, it will be assumed that the patient does not have severe heart failure. Renal insufficiency will be defined based on the latest estimated glomerular filtration rate (eGFR). If a patient is receiving renal replacement therapy, this will likewise be considered severe renal insufficiency. Hemodynamic instability will be defined based on a need for high-dose continuous vasopressor therapy specifically a noradrenalin dose > 0.3 μg/kg/min. If the patient is receiving other vasopressors instead of or in addition to noradrenalin, a noradrenaline-equivalent dose will be estimated based on prior formulas.39 In fertile women (age < 50 years) a negative urine-hCG or plasma-hCG must be present before enrolment. In order to optimize the chances of patients surviving to 72 hours (the time of the primary outcome), patients with limitations of care (including limitations related to mechanical ventilation and renal replacement therapy but not cardiopulmonary resuscitation) and patients with anticipated death within 24 hours, as judged by the treating clinician, will be excluded.