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)

Abstract Background Thiazide or thiazide-like diuretics associated hyponatremia (TAH) has a high prevalence in hospitalized patients. Patients might present either with hypovolemic hyponatremia due to volume loss as a diuretic effect of thiazide or with a thiazide-induced syndrome of inadequate anti...

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Main Authors: Karin Vogt, David Widmer, Mark Kirsch, Mirjam Christ-Crain, Laura Potasso
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Trials
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Online Access:https://doi.org/10.1186/s13063-025-08925-4
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author Karin Vogt
David Widmer
Mark Kirsch
Mirjam Christ-Crain
Laura Potasso
author_facet Karin Vogt
David Widmer
Mark Kirsch
Mirjam Christ-Crain
Laura Potasso
author_sort Karin Vogt
collection DOAJ
description Abstract Background Thiazide or thiazide-like diuretics associated hyponatremia (TAH) has a high prevalence in hospitalized patients. Patients might present either with hypovolemic hyponatremia due to volume loss as a diuretic effect of thiazide or with a thiazide-induced syndrome of inadequate antidiuresis-like hyponatremia in need of fluid restriction. Sodium-based urine indices are usually not able to differentiate these two, being directly influenced by thiazide itself. Current guidelines suggest the use of clinical hydration status assessment in patients with TAH, but this approach has a poor diagnostic performance. In a retrospective analysis, we found apparent strong ion difference (aSID) as well as chloride and potassium levels in urine (ChU) to be helpful in the differential diagnosis of TAH. Methods This is a randomized (1:1 ratio) controlled, superiority, parallel-group single-center trial. In total, 136 participants with TAH < 130 mmol/l will be enrolled and randomly assigned to undergo either aSID/ChU-guided therapy of TAH or standard of care during hospitalization. At baseline, hydration status will be assessed by history/clinical examination and ultrasound. The primary outcome is the percentage of patients with an increase in serum sodium level > 4 mmol/l at day 1 or > 134 mmol/l in a maximum of 3 days in the aSID/ChU guided therapy group as compared to the standard care group. Discussion This study will prospectively investigate whether the implementation of 2 new diagnostic indices (aSID and, if inconclusive, ChU) allows for a correct treatment of TAH. As a secondary outcome, the performance of clinical and ultrasound-guided hydration status assessment will be investigated. Trial registration ClinicalTrials.gov, identifier: NCT06381934 . Registered on 19 April 2024. www.kofam.ch , identifier: SNCTP 000005848/BASEC2024-00335.
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spelling doaj-art-35f7b07dc51c4225aba48b8ee60263f42025-08-20T04:03:06ZengBMCTrials1745-62152025-07-0126111310.1186/s13063-025-08925-4Validation 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)Karin Vogt0David Widmer1Mark Kirsch2Mirjam Christ-Crain3Laura Potasso4Department of Endocrinology, Diabetology and Metabolism, University Hospital BaselDivision of Internal Medicine, University Hospital BaselDivision of Internal Medicine, University Hospital BaselDepartment of Endocrinology, Diabetology and Metabolism, University Hospital BaselDepartment of Endocrinology, Diabetology and Metabolism, University Hospital BaselAbstract Background Thiazide or thiazide-like diuretics associated hyponatremia (TAH) has a high prevalence in hospitalized patients. Patients might present either with hypovolemic hyponatremia due to volume loss as a diuretic effect of thiazide or with a thiazide-induced syndrome of inadequate antidiuresis-like hyponatremia in need of fluid restriction. Sodium-based urine indices are usually not able to differentiate these two, being directly influenced by thiazide itself. Current guidelines suggest the use of clinical hydration status assessment in patients with TAH, but this approach has a poor diagnostic performance. In a retrospective analysis, we found apparent strong ion difference (aSID) as well as chloride and potassium levels in urine (ChU) to be helpful in the differential diagnosis of TAH. Methods This is a randomized (1:1 ratio) controlled, superiority, parallel-group single-center trial. In total, 136 participants with TAH < 130 mmol/l will be enrolled and randomly assigned to undergo either aSID/ChU-guided therapy of TAH or standard of care during hospitalization. At baseline, hydration status will be assessed by history/clinical examination and ultrasound. The primary outcome is the percentage of patients with an increase in serum sodium level > 4 mmol/l at day 1 or > 134 mmol/l in a maximum of 3 days in the aSID/ChU guided therapy group as compared to the standard care group. Discussion This study will prospectively investigate whether the implementation of 2 new diagnostic indices (aSID and, if inconclusive, ChU) allows for a correct treatment of TAH. As a secondary outcome, the performance of clinical and ultrasound-guided hydration status assessment will be investigated. Trial registration ClinicalTrials.gov, identifier: NCT06381934 . Registered on 19 April 2024. www.kofam.ch , identifier: SNCTP 000005848/BASEC2024-00335.https://doi.org/10.1186/s13063-025-08925-4SodiumThiazide-associated hyponatremiaVolume statusHydration statusASIDStewart model
spellingShingle Karin Vogt
David Widmer
Mark Kirsch
Mirjam Christ-Crain
Laura Potasso
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
Sodium
Thiazide-associated hyponatremia
Volume status
Hydration status
ASID
Stewart model
title 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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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
topic Sodium
Thiazide-associated hyponatremia
Volume status
Hydration status
ASID
Stewart model
url https://doi.org/10.1186/s13063-025-08925-4
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