Targeted Correction of Plasma Sodium Levels in Hospitalized Patients With Hyponatremia

NCT03557957 | Completed DMC

• 1 other identifier: HIT-trial
• Study Type: interventional
• Target: 2,278
• Locations: 5 countries
• Sites: 9

Brief Summary

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.

Conditions

Hyponatremia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

• 30 days mortality rate

  30 days

• 1 year mortality rate

  1 year

• 30 days rehospitalization rate

  30 days

• 1 year rehospitalization rate

  1 year

• Time to rehospitalization

  up to 1 year

Study Arms (2)

Standard care plus targeted correction of hyponatremia

EXPERIMENTAL

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

Standard care

ACTIVE COMPARATOR

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

Interventions

Targeted correction of plasma sodium levels OTHER

Targeted correction of hyponatremia

Standard care plus targeted correction of hyponatremia

Standard care OTHER

Standard care of hyponatremia

Standard care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult hospitalised patients with hypotonic hyponatremia \<130mmol/L

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Erasmus Medical Center: collaborator
• Cantonal Hospital of Aarau, Switzerland: collaborator
• Spital Solothurn, Switzerland: collaborator
• Cantonal Hospital of St. Gallen: collaborator
• Kantonsspital Liestal, Switzerland: collaborator
• Universitätsklinikum Köln: collaborator
• KBC Zagreb, Croatia: collaborator
• Azienda Ospedaliero-Universitaria Careggi: collaborator

Study Sites (9)

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Careggi University Hospital Florence

Florence, 50134, Italy

Location

Erasmus Medical Center Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

University Hospital Basel, Department of Endocrinology

Basel, Canton of Basel-City, 4031, Switzerland

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Kantosspital St. Gallen

Sankt Gallen, 9000, Switzerland

Location

Solothurner Spitäler AG

Solothurn, 4500, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 34552947 DERIVED

MeSH Terms

Conditions

Hyponatremia

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Mirjam Christ-Crain, Prof. MD

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors will be blinded to allocated treatment group
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled, parallel-group trial

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: June 15, 2018
• Study Start: August 20, 2018
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: July 11, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

IT (1); CR (1); NL (1); CH (5); DE (1)