Validation of New Diagnostic Indices to Simplify Hyponatremia Therapy Assessment in Patients on Thiazide Diuretics

Validation of Diagnostic Indices to Simplify Hyponatremia Therapy Assessment - A Randomized, Controlled, Parallel-group Clinical Trial in Hospitalized Patients on Thiazide Diuretics (THAT Study)

This study is looking at two new parameters, aSID and ChU, to see if these can help physicians to distinguish between different causes of low sodium levels (hyponatremia) in Patients taking a medicament against high blood pressure (thiazide). Researchers also want to see if using these new parameters to decide on treatment works just as well, or better, than the current standard treatments.

Study Overview

• Status: Recruiting
• Conditions: Thiazide Associated Hyponatremia
• Intervention / Treatment: Other: Standard Care; Other: aSID/ChU Guided Therapy

Detailed Description

Thiazide or thiazide-like diuretics associated hyponatremia (thiazide associated hyponatremia, TAH) has a high prevalence in hospitalized patients. Patients might present either with a hypovolemic hyponatremia due to volume loss as a diuretic effect of thiazide, or with a syndrome of inadequate antidiuresis (SIAD) like hyponatremia in need of fluid restriction. Canonical urine indices are not useful in differential diagnosis, being directly influenced by thiazide itself. Current guidelines suggest the use of a clinical volume status assessment, but this approach has a poor diagnostic performance, with less than 50% of patients being rightly diagnosed thru that. The investigators showed in a retrospective analysis the possible role of strong apparent ion difference (aSID) and of chloride and potassium levels in urine (ChU) in differential diagnosis of TAH. The goal of this study is to investigate prospectively whether implementation of aSID and, in case of inconclusive aSID, ChU, allows a correct differential diagnosis and treatment of TAH.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Potasso, Dr. med. sc.; Phone Number: +41 61 328 58 76; Email: laura.potasso@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • University Hospital Basel
    • Contact: Laura Potasso, Dr. med. sc.; Phone Number: +41 61 328 58 76; Email: laura.potasso@usb.ch
    • Contact: Mirjam Christ-Crain, Prof. Dr. med.; Phone Number: +41 61 328 70 80; Email: mirjam.christ-crain@usb.ch
    • Principal Investigator: Laura Potasso, Dr. med. sc.
    • Sub-Investigator: Mirjam Christ-Crain, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Hospitalized patients presenting at University Hospital Basel
• aged 18 years or older
• able to give informed consent as documented by signature
• with serum sodium level < 133 mmol/l and serum osmolality < 300 mOsm/kg
• with treatment with thiazide or thiazide-like diuretic

Exclusion Criteria:

• symptomatic hyponatremia in need of 3% hypertonic solution or intensive care treatment
• inability or contraindications to undergo the trial (i.e., any acute severe cardiovascular event requiring an immediate intervention)
• decompensated liver cirrhosis CHILD C
• decompensated heart failure NYHA III or higher
• severe valve impairment
• untreated adrenal insufficiency
• severe kidney disease in need of dialysis
• pregnancy or breastfeeding
• end of life care
• inability to follow the study procedures (i.e., language problem, dementia or critical illness).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Care Group; TAH patients randomised to the Standard Care Group will be followed by a physician not involved in the study.	Other: Standard Care; Standard diagnosis and therapy procedures at physician's discretion.
Active Comparator: aSID/ChU Guided Therapy Group; TAH patients randomised to the aSID/ChU Guided Therapy Group will have aSID and ChU determined and, depending on the results, will be assigned to fluid administration with saline or drinking restriction.	Other: aSID/ChU Guided Therapy; Stopping of thiazide therapy. Measure aSID: aSID between 39 and 42 mmol/l : measure ChUChU lower than 15mmol/l : fluid administration (0.9% NaCl infusion, 250-500 ml over 2 hours followed by 10-20 ml/kg/24h)ChU higher than 14.9 mmol/l : drinking restriction (of at least 50% of usual drinking volume); aSID higher than 42 mmol/l : fuid administration (fluid administration (0.9% NaCl infusion, 250-500 ml over 2 hours followed by 10-20 ml/kg/24h); aSID lower than 39 mmol/l : drinking restriction (of at least 50% of usual drinking volume) The aSID/ChU guided therapy will take place for a minimum of 1- and a maximum of 3 days after enrolment. Treatment and adherence to the treatment will be assessed and re-evaluated at least daily for 3 days or till discharge or sodium normalization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Sodium Level	Percentage of patients with an increase in serum sodium level > 4 mmol/l at day 1 or > 134 mmol/l in maximum 3 days in the aSID/ChU guided therapy group as compared to the standard care (control) group.	at baseline, 24 hours and up to 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Descriptive analyses: Changes in aSID in relation to changes in serum sodium levels	Descriptive analyses: Changes in aSID in relation to changes in serum sodium levels.	at baseline, 24 hours and up to 72 hours
Descriptive analyses: Changes in ChU in relation to changes in serum sodium levels	Descriptive analyses: Changes in ChU in relation to changes in serum sodium levels.	at baseline, 24 hours and up to 72 hours
Diagnostic performance analyses of: aSID and ChU	Sensibility, specificity, negative predictive value and positive predictive value at different cut-offs for adequate therapy of TAH. An adequate therapy of TAH is a therapy by which the patient reaches the primary endpoint independent from randomization arm.	at baseline, 24 hours and up to 72 hours
Diagnostic performance analyses of: aSID measured in blood gas analysis	Sensibility, specificity, negative predictive value and positive predictive value at different cut-offs for adequate therapy of TAH. An adequate therapy of TAH is a therapy by which the patient reaches the primary endpoint independent from randomization arm.	at baseline, 24 hours and up to 72 hours
Diagnostic performance analyses of: clinical volume status assessment	Sensibility, specificity, negative predictive value and positive predictive value at different cut-offs for adequate therapy of TAH. An adequate therapy of TAH is a therapy by which the patient reaches the primary endpoint independent from randomization arm.	at baseline, 24 hours and up to 72 hours
Diagnostic performance analyses of: not-invasive instrumental volume status assessment	Sensibility, specificity, negative predictive value and positive predictive value at different cut-offs for adequate therapy of TAH. An adequate therapy of TAH is a therapy by which the patient reaches the primary endpoint independent from randomization arm.	at baseline, 24 hours and up to 72 hours
Diagnostic performance analyses of: other hormones such as aldosterone, renin, arginine-vasopressin	Sensibility, specificity, negative predictive value and positive predictive value at different cut-offs for adequate therapy of TAH. An adequate therapy of TAH is a therapy by which the patient reaches the primary endpoint independent from randomization arm.	at baseline, 24 hours and up to 72 hours

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Laura Potasso, Dr. med. sc., University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Vogt K, Widmer D, Kirsch M, Christ-Crain M, Potasso L. Validation of new diagnostic indices to simplify hyponatremia therapy assessment in patients on thiazide diuretics: study protocol of a randomized, controlled, parallel-group trial (THAT-Study). Trials. 2025 Jul 11;26(1):242. doi: 10.1186/s13063-025-08925-4.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Hyponatremia; Strong Apparent Ion Difference; Potassium Levels in Urine
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Nutritional and Metabolic Diseases; Hyponatremia; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: 2024-00335; kt23ChristCrain4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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