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

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.

Study Overview

• Status: Completed
• Conditions: Hyponatremia
• Intervention / Treatment: Other: Targeted correction of plasma sodium levels; Other: Standard care

• Study Type: Interventional
• Enrollment (Actual): 2278
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia, 10000
    • University hospital centre Zagreb
• Germany
  • Köln, Germany, 50937
    • Uniklinik Köln
• Italy
  • Firenze, Italy, 50134
    • Careggi University Hospital Florence
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medical Center Rotterdam
• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau
  • Liestal, Switzerland, 4410
    • Kantonsspital Baselland
  • Saint Gallen, Switzerland, 9000
    • Kantosspital St. Gallen
  • Solothurn, Switzerland, 4500
    • Solothurner Spitäler AG
  • Basel Stadt
    • Basel, Basel Stadt, Switzerland, 4031
      • University Hospital Basel, Department of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All adult hospitalised patients with hypotonic hyponatremia <130mmol/L
• Hospitalization of at least 24 h after inclusion in the study

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard care plus targeted correction of hyponatremia; 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.	Other: Targeted correction of plasma sodium levels; Targeted correction of hyponatremia
Active Comparator: Standard care; 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.	Other: Standard care; Standard care of hyponatremia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary outcome is the combined risk of death or rehospitalization within 30 days	Rate of death or rehospitalization within 30 days	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30 days mortality rate	Mortality rate	30 days
1 year mortality rate	Mortality rate	1 year
30 days rehospitalization rate	Rehospitalization rate	30 days
1 year rehospitalization rate	Rehospitalization rate	1 year
Time to rehospitalization	Days until first rehospitalization	up to 1 year
Time to death	Days until death	up to 1 year
length of hospital stay	length of index hospital stay in days	up to 1 year
Rate of falls	Number of falls	30 days
Rate of fractures	Number of bone fractures	30 days
Rate of fractures	Number of bone fractures	1 year
Rate of Plasma sodium normalization at discharge	Rate of Plasma sodium Levels >=135mmol/L at discharge	up to 1 year
Change in Plasma sodium Levels	Change in mmol/L in Plasma sodium Levels from inclusion to discharge	up to 1 year
Recurrence of hyponatremia	Rate of recurrence of hyponatremia	30 days
Recurrence of hyponatremia	Rate of recurrence of hyponatremia	1 year
Severely symptomatic hyponatremia	Rate of severely symptomatic hyponatremia requiring intensive care Treatment during index hospitalization	up to 1 year
Sodium-overcorrection	Rate of plasma sodium overcorrection during index hospitalization	up to 1 year
number of adverse events	Rate of adverse events	30 days
number of adverse events	Rate of adverse events	1 year
Severe adverse events	Rate of severe adverse events	30 days
Severe adverse events	Rate of severe adverse events	1 year
Diagnostic accuracy of copeptin in the diagnosis of hyponatremia	Copeptin Level will be correlated with final hyponatremia diagnosis	1 day
Diagnostic accuracy of mid-regional mid-regional (MR)-proANP in the diagnosis of hyponatremia	MR-proANP Level will be correlated with final hyponatremia diagnosis N-terminal (NT)-proBNP, aldosterone, renin)	1 day
Diagnostic accuracy of NT-proBNP in the diagnosis of hyponatremia	NT-proBNP Level will be correlated with final hyponatremia diagnosis	1 day
Diagnostic accuracy of aldosterone in the diagnosis of hyponatremia	Aldosterone Level will be correlated with final hyponatremia diagnosis	1 day
Diagnostic accuracy of renin in the diagnosis of hyponatremia	Renin Level will be correlated with final hyponatremia diagnosis	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Erasmus Medical Center; Cantonal Hospital of Aarau, Switzerland; Azienda Ospedaliero-Universitaria Careggi; Universitätsklinikum Köln; Spital Solothurn, Switzerland; Kantonsspital St. Gallen, Switzerland; Kantonsspital Liestal, Switzerland; KBC Zagreb, Croatia
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof. MD, University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2018
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: May 16, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): July 11, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyponatremia
• Other Study ID Numbers: HIT-trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No