Targeted Correction of Plasma Sodium Levels in Hospitalized Patients With Hyponatremia (HIT)

Targeted Correction of Plasma Sodium Levels in Hospitalized Patients With Hyponatremia: a Randomized, Controlled, Parallel-group Trial

Erasmus Medical Center, Cantonal Hospital of Aarau, Switzerland, Spital Solothurn, Switzerland, Kantonsspital St. Gallen, Switzerland, Kantonsspital Liestal, Switzerland, Uniklinik Köln, Germany, KBC Zagreb, Croatia, Azienda Ospedaliero Universitaria Careggi, Italy

Hyponatremia is the most common electrolyte disorder with a prevalence of up to 30% in hospitalized patients. While treatment of acute hyponatremia with severe clinical symptoms due to cerebral edema is undisputed and straightforward, hyponatremia in general is usually considered asymptomatic or not clinically relevant. Accordingly, a recent observational study showed that appropriate laboratory tests to evaluate the etiology of hyponatremia were obtained in less than 50% of patients, leading to 75% of patients being still hyponatremic at discharge. This is problematic in the context of increasing evidence, revealing an association of chronic hyponatremia with adverse effects such as gait alterations and falls, attention deficits, bone loss and fractures as well as disease-associated morbidity leading to increased rates of readmissions and mortality. Yet, there is a complete lack of randomized clinical trials with the primary aim to investigate whether correction of plasma sodium concentration counteracts the elevated risk of rehospitalization and mortality. The aim of this trial is therefore to determine the effects on mortality and rehospitalization rate of a targeted correction of plasma sodium concentration in addition to current standard care in hospitalized hyponatremic patients.

Diagnosis and treatment of hyponatremia will be standardized according to the European Clinical Practice Guidelines (ECPG). Treatment response and adherence will be evaluated daily and treatment adapted if treatment goals are not reached.Targeted correction of plasma sodium Levels.

Diagnosis and treatment of hyponatremia will be solely at the discretion of the attending physicians who are in no way involved in the trial. The study team will not intervene with the treatment in any way. Diagnostic and treatment decisions as well as course of the plasma sodium level will only be recorded after patient is discharged from hospital using the medical records and patient charts. It will be generally recommended to measure plasma sodium levels 3x weekly or more frequently if clinically indicated, at discharge and after 30 days.

Rate of severely symptomatic hyponatremia requiring intensive care Treatment during index hospitalization

MR-proANP Level will be correlated with final hyponatremia diagnosis N-terminal (NT)-proBNP, aldosterone, renin)

Inclusion Criteria: All adult hospitalised patients with hypotonic hyponatremia <130mmol/L Exclusion Criteria: severe symptomatic hyponatremia in need of intensive care treatment non-hypotonic hyponatremia with plasma osmolality >280 milliosmol (mOsm)/kg end of life care (palliative treatment)

Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on the public repository dataverse.harvard.edu.

Refardt J, Pelouto A, Potasso L, Hoorn EJ, Christ-Crain M. Hyponatremia Intervention Trial (HIT): Study Protocol of a Randomized, Controlled, Parallel-Group Trial With Blinded Outcome Assessment. Front Med (Lausanne). 2021 Sep 6;8:729545. doi: 10.3389/fmed.2021.729545. eCollection 2021.