Thiazide-induced Hyponatremia (TIH)PROPHECYNCT05542056
Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia
An observational study of Thiazide-induced Hyponatremia (TIH), run by University Hospital, Basel, Switzerland at 3 sites in 2 countries.
Trial summary
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thiazide-induced Hyponatremia (TIH)
- What is being tested?
- Data and biosample collection
- How many people
- 232 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 26 Sep 2022to Jul 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed. Screening will take place at the University Hospital Basel and Kantonsspital Baselland, primarily at the Endocrine Outpatient Clinic and the Hypertension Clinic of the Medical Outpatient Clinic or Nephrology Department and is based on the patients' charts as well as consultation with the treating physician.
Who may be able to join
- Newly prescribed thiazide or thiazide-like diuretic
- ≥ 18 years of age
- Informed Consent as documented by signature
Who cannot join
- Intake of thiazide or thiazide-like diuretic in the preceding month
- Hyponatremia (plasma sodium <135 mmol/L) at baseline
- Acute infectious / inflammatory disease (CRP ≥ 20 mg/L [1, 11])
- Symptomatic urinary tract infection
- Chronic treatment with NSAID and / or NSAID intake 48 hours prior to urine sampling at visit 1 and 2 (intake of acetylsalicylic acid will be no exclusion criteria)
- End of life care, no informed consent or inability to follow the procedures of the study, e.g., due to language barriers, psychological disorders, dementia
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Joyce Santos de Jesus contact
3 sites in 2 countries
Switzerland2 sites, 2 recruiting
- Recruiting
University Hospital Basel, Endocrinology, Diabetes and Metabolism
Basel, 4031
Julia Beck, Dr. med., +41 61 328 54 37, julia.beck@usb.ch
Julia Beck, Dr. med.
- Recruiting
Kantonsspital Baselland
Liestal, 4410
Felix Burkhalter Pirovino, Dr. med.
Felix Burkhalter Pirovino, Dr. med.
Spain1 site, 1 recruiting
- Recruiting
Hospital Universitario de Móstoles
Móstoles, 28935
Alberto Fernandez Martinez, Prof. Dr. med., afernamed@hotmail.com
About this study
Official title: Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia: a Prospective Cohort Study (The PROPHECY Study)
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment.
Read the detailed description
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. They act by inhibiting the apical Na+-Cl- -cotransporter in the distal convoluted tubules of the kidneys. Thiazides and thiazide-like diuretics often cause adverse effects, importantly a drop in plasma sodium levels that is called thiazide-induced hyponatremia (TIH). Data suggest a crucial role of urinary PGE2 in water reabsorption. Since urinary PGE2 concentrations were higher in patients with TIH, quantification of urinary PGE2 prior and after thiazide initiation might allow identification of patients at risk for TIH, presenting PGE2 as a potential novel predictive marker for the development of TIH.
This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment. Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed are screened for inclusion.
The study procedure contains the screening and inclusion, visit 1 before thiazide initiation, visit 2 4 weeks (+/-7days) after thiazide initiation and a 3-months follow-up (visit 3). An additional visit (visit 2.1) will only be added in case of a dose change of the thiazide or thiazide-like diuretic (4 weeks +/- 7 days after the dose change). The 2 hours- challenge is optional if the patient agrees to additional testing.
- Conditions
- Thiazide-induced Hyponatremia (TIH)
- Being tested
- Data and biosample collection
- Keywords
- Thiazide, Thiazide-like diuretics, Hyponatremia, Prostaglandin E2 (PGE2), Urinary PGE2 concentration, Plasma sodium level, Urinary prostaglandins
- Medical subject headings
- Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Data and biosample collectionOther
Collection of spot urine, blood sampling, vital parameters, body weight, medical history, patient questionnaires, drinking protocol, drug diary at at Visit 1 (before thiazide initiation), at Optional 2 hours-challenge, at Visit 2 (4 weeks after thiazide initiation), at Visit 2.1 (4 weeks after dose change), at Visit 3 (3-months after thiazide initiation)
| Study group | Role | What they receive |
|---|---|---|
| Patients with newly prescribed thiazide or thiazide-like diuretic | As the study population of this observational study shall be as representative as possible all patients with a new thiazide or thiazide-like diuretic regardless of the indication, co-morbidities and co-medication can be included. Receives: Other: Data and biosample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of hyponatremia (plasma sodium <135 mmol/L)
Occurrence of hyponatremia (plasma sodium <135 mmol/L)
Measured: Within the first four weeks of treatment (at visit 2)
Secondary outcomes (19)
Change in urinary Prostaglandin- concentration
Change in urinary Prostaglandin E2 (PGE2) and metabolite (PGE2M)- concentration
Measured: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in the expression of proteins involved in sodium and water transport
Change in the expression of proteins involved in sodium and water transport (AQP2, Prostaglandin transporter (PGT) and NCC) in urinary extracellular vesicles in spot urine (second morning urine)
Measured: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in systolic and diastolic blood pressure
Change in systolic and diastolic blood pressure
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in heart rate
Change in heart rate
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in body weight
Change in body weight
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in daily fluid intake
Change in daily fluid intake
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in Bioelectrical impedance analysis (BIA)
Change in Bioelectrical impedance analysis (BIA)
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in plasma sodium
Change in plasma sodium
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urine sodium
Change in urine sodium
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in potassium
Change in potassium
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in chloride
Change in chloride
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in creatinine
Change in creatinine
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urea
Change in urea
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in uric acid
Change in uric acid
Measured: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in general well-being
Change in general well-being rated on a visual analogue scale reaching from 0 to 10
Measured: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Incidence of hyponatremia
Incidence of hyponatremia
Measured: Between baseline and visit 3, approximately 3 months
Incidence of falls
Incidence of falls
Measured: Between baseline and visit 3, approximately 3 months
Incidence of fractures
Incidence of fractures
Measured: Between baseline and visit 3, approximately 3 months
Incidence of hospitalization due to any cause
Incidence of hospitalization due to any cause
Measured: Between baseline and visit 3, approximately 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2022
- Study start26 Sep 2022
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thiazide-induced Hyponatremia (TIH)Studies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 232 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof. Dr. med., Principal investigator, University Hospital Basel, Endocrinology, Diabetes and Metabolism
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05542056
- Sponsor's protocol ID
- 2022-01241; kt21ChristCrain3
- Acronym
- PROPHECY
- Status last verified
- Jun 2025
- First submitted
- 12 Sep 2022
- Last updated
- 1 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia: a Prospective Cohort Study (The PROPHECY Study)
- ClinicalTrials.gov ID
- NCT05542056
- Acronym / sponsor ID
- PROPHECY / 2022-01241; kt21ChristCrain3
- Conditions
- Thiazide-induced Hyponatremia (TIH)
- Keywords
- Thiazide, Thiazide-like diuretics, Hyponatremia, Prostaglandin E2 (PGE2), Urinary PGE2 concentration, Plasma sodium level, Urinary prostaglandins
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 232 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 26 Sep 2022 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 15 Sep 2022 (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.
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment.
Detailed description
Thiazides and thiazide-like diuretics are one of the five major classes of antihypertensive drugs. They act by inhibiting the apical Na+-Cl- -cotransporter in the distal convoluted tubules of the kidneys. Thiazides and thiazide-like diuretics often cause adverse effects, importantly a drop in plasma sodium levels that is called thiazide-induced hyponatremia (TIH). Data suggest a crucial role of urinary PGE2 in water reabsorption. Since urinary PGE2 concentrations were higher in patients with TIH, quantification of urinary PGE2 prior and after thiazide initiation might allow identification of patients at risk for TIH, presenting PGE2 as a potential novel predictive marker for the development of TIH.
This study is to investigate whether urinary PGE2 concentration at baseline (prior to thiazide initiation) is associated with the development of TIH within the first four weeks of treatment. Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed are screened for inclusion.
The study procedure contains the screening and inclusion, visit 1 before thiazide initiation, visit 2 4 weeks (+/-7days) after thiazide initiation and a 3-months follow-up (visit 3). An additional visit (visit 2.1) will only be added in case of a dose change of the thiazide or thiazide-like diuretic (4 weeks +/- 7 days after the dose change). The 2 hours- challenge is optional if the patient agrees to additional testing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with newly prescribed thiazide or thiazide-like diuretic | – | Other: Data and biosample collectionAs the study population of this observational study shall be as representative as possible all patients with a new thiazide or thiazide-like diuretic regardless of the indication, co-morbidities and co-medication can be included. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hospitalized and ambulatory patients in whom a thiazide or thiazide-like diuretic will be newly prescribed. Screening will take place at the University Hospital Basel and Kantonsspital Baselland, primarily at the Endocrine Outpatient Clinic and the Hypertension Clinic of the Medical Outpatient Clinic or Nephrology Department and is based on the patients' charts as well as consultation with the treating physician.
Key inclusion criteria (3 listed)
- Newly prescribed thiazide or thiazide-like diuretic
- ≥ 18 years of age
- Informed Consent as documented by signature
Key exclusion criteria (6 listed)
- Intake of thiazide or thiazide-like diuretic in the preceding month
- Hyponatremia (plasma sodium <135 mmol/L) at baseline
- Acute infectious / inflammatory disease (CRP ≥ 20 mg/L [1, 11])
- Symptomatic urinary tract infection
- Chronic treatment with NSAID and / or NSAID intake 48 hours prior to urine sampling at visit 1 and 2 (intake of acetylsalicylic acid will be no exclusion criteria)
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 |
|---|---|---|
| Data and biosample collectionCollection of spot urine, blood sampling, vital parameters, body weight, medical history, patient questionnaires, drinking protocol, drug diary at at Visit 1 (before thiazide initiation), at Optional 2 hours-challenge, at Visit 2 (4 weeks after thiazide initiation), at Visit 2.1 (4 weeks after dose change), at Visit 3 (3-months after thiazide initiation) | Other | Patients with newly prescribed thiazide or thiazide-like diuretic |
Primary outcome
Occurrence of hyponatremia (plasma sodium <135 mmol/L)
Time frame: Within the first four weeks of treatment (at visit 2)
Occurrence of hyponatremia (plasma sodium <135 mmol/L)
19 secondary outcomes
Change in urinary Prostaglandin- concentration
Time frame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in the expression of proteins involved in sodium and water transport
Time frame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
Change in systolic and diastolic blood pressure
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in heart rate
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in body weight
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in daily fluid intake
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in Bioelectrical impedance analysis (BIA)
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Change in plasma sodium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urine sodium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in potassium
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in chloride
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in creatinine
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in urea
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in uric acid
Time frame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
Change in general well-being
Time frame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
Incidence of hyponatremia
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of falls
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of fractures
Time frame: Between baseline and visit 3, approximately 3 months
Incidence of hospitalization due to any cause
Time frame: Between baseline and visit 3, approximately 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
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.
Joyce Santos de Jesus contact
Mirjam Christ-Crain, Prof. Dr. med. principal investigator
University Hospital Basel, Endocrinology, Diabetes and Metabolism
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thiazide-induced Hyponatremia (TIH), run by University Hospital, Basel, Switzerland at 3 sites in 2 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 3 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 1 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 3 sites in Switzerland, Spain. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia Beck, Dr. med. (+41 61 328 54 37, julia.beck@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of hyponatremia (plasma sodium <135 mmol/L) (time frame: Within the first four weeks of treatment (at visit 2)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jul 2025.