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

Official title

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

Overview

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.

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.

Interventions

• Other Standard Care
  Standard diagnosis and therapy procedures at physician's discretion.
• Other aSID/ChU Guided Therapy
  Stopping of thiazide therapy. Measure aSID: * aSID between 39 and 42 mmol/l : measure ChU * ChU 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

Primary outcome measures

• Serum Sodium Level [Time frame: at baseline, 24 hours and up to 72 hours]

Secondary outcome measures (7)

• Descriptive analyses: Changes in aSID in relation to changes in serum sodium levels [Time frame: at baseline, 24 hours and up to 72 hours]
• Descriptive analyses: Changes in ChU in relation to changes in serum sodium levels [Time frame: at baseline, 24 hours and up to 72 hours]
• Diagnostic performance analyses of: aSID and ChU [Time frame: at baseline, 24 hours and up to 72 hours]
• Diagnostic performance analyses of: aSID measured in blood gas analysis [Time frame: at baseline, 24 hours and up to 72 hours]
• Diagnostic performance analyses of: clinical volume status assessment [Time frame: at baseline, 24 hours and up to 72 hours]
• Diagnostic performance analyses of: not-invasive instrumental volume status assessment [Time frame: at baseline, 24 hours and up to 72 hours]
• Diagnostic performance analyses of: other hormones such as aldosterone, renin, arginine-vasopressin [Time frame: at baseline, 24 hours and up to 72 hours]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Switzerland · 1 center

• University Hospital Basel — Basel

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. PMID 40646556

Identifiers

NCT: NCT06381934 · 2024-00335; kt23ChristCrain4

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗