Clinical trial NCT05542056: Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia
Official title: Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia: a Prospective Cohort Study (The PROPHECY Study)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Thiazide-induced Hyponatremia (TIH)
Keywords: Thiazide
Thiazide-like diuretics
Hyponatremia
Prostaglandin E2 (PGE2)
Urinary PGE2 concentration
Plasma sodium level
Urinary prostaglandins
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2022-09-15
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* Newly prescribed thiazide or thiazide-like diuretic
* ≥ 18 years of age
* Informed Consent as documented by signature

Exclusion Criteria:

* 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

Primary outcomes:
measure: Occurrence of hyponatremia (plasma sodium <135 mmol/L)
timeFrame: Within the first four weeks of treatment (at visit 2)
Secondary outcomes:
measure: Change in urinary Prostaglandin- concentration
timeFrame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in the expression of proteins involved in sodium and water transport
timeFrame: Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in systolic and diastolic blood pressure
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in heart rate
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in body weight
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in daily fluid intake
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in Bioelectrical impedance analysis (BIA)
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Change in plasma sodium
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in urine sodium
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in potassium
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in chloride
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in creatinine
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in urea
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in uric acid
timeFrame: Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks
measure: Change in general well-being
timeFrame: Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months
measure: Incidence of hyponatremia
timeFrame: Between baseline and visit 3, approximately 3 months
measure: Incidence of falls
timeFrame: Between baseline and visit 3, approximately 3 months
measure: Incidence of fractures
timeFrame: Between baseline and visit 3, approximately 3 months
measure: Incidence of hospitalization due to any cause
timeFrame: Between baseline and visit 3, approximately 3 months
Other outcomes:
Locations:
city: Móstoles
country: Spain
facility: Hospital Universitario de Móstoles
city: Basel
country: Switzerland
facility: University Hospital Basel, Endocrinology, Diabetes and Metabolism
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland
Study officials:
affiliation: University Hospital Basel, Endocrinology, Diabetes and Metabolism
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: