HyponatremiaHITNCT03557957
Targeted Correction of Plasma Sodium Levels in Hospitalized Patients With Hyponatremia
A study testing Targeted correction of plasma sodium levels in people with Hyponatremia, run by University Hospital, Basel, Switzerland at 9 sites in 5 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Targeted correction of plasma sodium levels
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,278 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 20 Aug 2018to 30 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All adult hospitalised patients with hypotonic hyponatremia <130mmol/L
- Hospitalization of at least 24 h after inclusion in the study
Who cannot join
- 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)
Trial locations and contacts
9 sites in 5 countries.
9 sites in 5 countries
Switzerland5 sites
Kantonsspital Aarau
Aarau, 5001
University Hospital Basel, Department of Endocrinology
Basel, Canton of Basel-City, 4031
Kantonsspital Baselland
Liestal, 4410
Kantosspital St. Gallen
Sankt Gallen, 9000
Solothurner Spitäler AG
Solothurn, 4500
About this study
Official title: 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.
- Conditions
- Hyponatremia
- Being tested
- Targeted correction of plasma sodium levels, Standard care
- Medical subject headings
- Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Targeted correction of plasma sodium levelsOther
Targeted correction of hyponatremia
Standard careOther
Standard care of hyponatremia
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome is the combined risk of death or rehospitalization within 30 days
Rate of death or rehospitalization within 30 days
Measured: 30 days
Secondary outcomes (25)
30 days mortality rate
Mortality rate
Measured: 30 days
1 year mortality rate
Mortality rate
Measured: 1 year
30 days rehospitalization rate
Rehospitalization rate
Measured: 30 days
1 year rehospitalization rate
Rehospitalization rate
Measured: 1 year
Time to rehospitalization
Days until first rehospitalization
Measured: up to 1 year
Time to death
Days until death
Measured: up to 1 year
length of hospital stay
length of index hospital stay in days
Measured: up to 1 year
Rate of falls
Number of falls
Measured: 30 days
Rate of fractures
Number of bone fractures
Measured: 30 days
Rate of fractures
Number of bone fractures
Measured: 1 year
Rate of Plasma sodium normalization at discharge
Rate of Plasma sodium Levels >=135mmol/L at discharge
Measured: up to 1 year
Change in Plasma sodium Levels
Change in mmol/L in Plasma sodium Levels from inclusion to discharge
Measured: up to 1 year
Recurrence of hyponatremia
Rate of recurrence of hyponatremia
Measured: 30 days
Recurrence of hyponatremia
Rate of recurrence of hyponatremia
Measured: 1 year
Severely symptomatic hyponatremia
Rate of severely symptomatic hyponatremia requiring intensive care Treatment during index hospitalization
Measured: up to 1 year
Sodium-overcorrection
Rate of plasma sodium overcorrection during index hospitalization
Measured: up to 1 year
number of adverse events
Rate of adverse events
Measured: 30 days
number of adverse events
Rate of adverse events
Measured: 1 year
Severe adverse events
Rate of severe adverse events
Measured: 30 days
Severe adverse events
Rate of severe adverse events
Measured: 1 year
Diagnostic accuracy of copeptin in the diagnosis of hyponatremia
Copeptin Level will be correlated with final hyponatremia diagnosis
Measured: 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)
Measured: 1 day
Diagnostic accuracy of NT-proBNP in the diagnosis of hyponatremia
NT-proBNP Level will be correlated with final hyponatremia diagnosis
Measured: 1 day
Diagnostic accuracy of aldosterone in the diagnosis of hyponatremia
Aldosterone Level will be correlated with final hyponatremia diagnosis
Measured: 1 day
Diagnostic accuracy of renin in the diagnosis of hyponatremia
Renin Level will be correlated with final hyponatremia diagnosis
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start20 Aug 2018
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HyponatremiaStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, controlled, parallel-group trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 2,278 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Cantonal Hospital of Aarau, Switzerland, Spital Solothurn, Switzerland, Cantonal Hospital of St. Gallen, Kantonsspital Liestal, Switzerland, Universitätsklinikum Köln, KBC Zagreb, Croatia, Azienda Ospedaliero-Universitaria Careggi
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof. MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03557957
- Sponsor's protocol ID
- HIT-trial
- Acronym
- HIT
- Status last verified
- Jul 2025
- First submitted
- 16 May 2018
- Last updated
- 11 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Refardt J, Potasso L, Pelouto A, Trappe M, Gregoriano C, Koster M, Vodanovic ID, Norello D, Ravioli S, Cukoski S, Boesing M, Ryser B, Sambula L, Rapsch N, Monnerat S, Beck J, Lustenberger S, Vogt DR, Werlen L, de Jesus JS, Bontognali M, Schuetz P, Zandbergen AAM, Peri A, Kastelan D, Lindner G, Leuppi J, Bilz S, Mueller B, Burst V, Hoorn EJ, Christ-Crain M. A Randomized Trial of Targeted Hyponatremia Correction in Hospitalized Patients. NEJM Evid. 2026 Mar;5(3):EVIDoa2500086. doi: 10.1056/EVIDoa2500086. Epub 2026 Feb 24.
PubMed 41733398Refardt 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.
PubMed 34552947
Study at a glance
From the registry record, last updated by the sponsor on 11 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeted Correction of Plasma Sodium Levels in Hospitalized Patients With Hyponatremia: a Randomized, Controlled, Parallel-group Trial
- ClinicalTrials.gov ID
- NCT03557957
- Acronym / sponsor ID
- HIT / HIT-trial
- Conditions
- Hyponatremia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,278 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Cantonal Hospital of Aarau, Switzerland, Spital Solothurn, Switzerland, Cantonal Hospital of St. Gallen, Kantonsspital Liestal, Switzerland, Universitätsklinikum Köln, KBC Zagreb, Croatia, Azienda Ospedaliero-Universitaria Careggi
- Study start
- 20 Aug 2018 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 15 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, controlled, parallel-group trial
| Arm | Type | Receives |
|---|---|---|
| Standard care plus targeted correction of hyponatremia | Experimental | Other: Targeted correction of plasma sodium levelsDiagnosis 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. |
| Standard care | Active comparator | Other: Standard careDiagnosis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- All adult hospitalised patients with hypotonic hyponatremia <130mmol/L
- Hospitalization of at least 24 h after inclusion in the study
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Targeted correction of plasma sodium levelsTargeted correction of hyponatremia | Other | Standard care plus targeted correction of hyponatremia |
| Standard careStandard care of hyponatremia | Other | Standard care |
Primary outcome
The primary outcome is the combined risk of death or rehospitalization within 30 days
Time frame: 30 days
Rate of death or rehospitalization within 30 days
25 secondary outcomes
30 days mortality rate
Time frame: 30 days
1 year mortality rate
Time frame: 1 year
30 days rehospitalization rate
Time frame: 30 days
1 year rehospitalization rate
Time frame: 1 year
Time to rehospitalization
Time frame: up to 1 year
Time to death
Time frame: up to 1 year
length of hospital stay
Time frame: up to 1 year
Rate of falls
Time frame: 30 days
Rate of fractures
Time frame: 30 days
Rate of fractures
Time frame: 1 year
Rate of Plasma sodium normalization at discharge
Time frame: up to 1 year
Change in Plasma sodium Levels
Time frame: up to 1 year
Recurrence of hyponatremia
Time frame: 30 days
Recurrence of hyponatremia
Time frame: 1 year
Severely symptomatic hyponatremia
Time frame: up to 1 year
Sodium-overcorrection
Time frame: up to 1 year
number of adverse events
Time frame: 30 days
number of adverse events
Time frame: 1 year
Severe adverse events
Time frame: 30 days
Severe adverse events
Time frame: 1 year
Diagnostic accuracy of copeptin in the diagnosis of hyponatremia
Time frame: 1 day
Diagnostic accuracy of mid-regional mid-regional (MR)-proANP in the diagnosis of hyponatremia
Time frame: 1 day
Diagnostic accuracy of NT-proBNP in the diagnosis of hyponatremia
Time frame: 1 day
Diagnostic accuracy of aldosterone in the diagnosis of hyponatremia
Time frame: 1 day
Diagnostic accuracy of renin in the diagnosis of hyponatremia
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jul 2025.
- Derived from this study: PubMed 41733398Refardt J, Potasso L, Pelouto A, Trappe M, Gregoriano C, Koster M, Vodanovic ID, Norello D, Ravioli S, Cukoski S, Boesing M, Ryser B, Sambula L, Rapsch N, Monnerat S, Beck J, Lustenberger S, Vogt DR, Werlen L, de Jesus JS, Bontognali M, Schuetz P, Zandbergen AAM, Peri A, Kastelan D, Lindner G, Leuppi J, Bilz S, Mueller B, Burst V, Hoorn EJ, Christ-Crain M. A Randomized Trial of Targeted Hyponatremia Correction in Hospitalized Patients. NEJM Evid. 2026 Mar;5(3):EVIDoa2500086. doi: 10.1056/EVIDoa2500086. Epub 2026 Feb 24.
- Derived from this study: PubMed 34552947Refardt 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mirjam Christ-Crain, Prof. MD principal investigator
University Hospital, Basel, Switzerland
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Targeted correction of plasma sodium levels in people with Hyponatremia, run by University Hospital, Basel, Switzerland at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Switzerland, Croatia, Germany, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcome is the combined risk of death or rehospitalization within 30 days (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03557957, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2025.