Urinary Prostaglandin as a Potential Predictive Marker for Thiazide-induced Hyponatremia: a Prospective Cohort Study (The PROPHECY Study)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 232
- 试验地点
- 3
- 主要终点
- Occurrence of hyponatremia (plasma sodium <135 mmol/L)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly prescribed thiazide or thiazide-like diuretic
- •≥ 18 years of age
- •Informed Consent as documented by signature
排除标准
- •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
结局指标
主要结局
Occurrence of hyponatremia (plasma sodium <135 mmol/L)
时间窗: Within the first four weeks of treatment (at visit 2)
Occurrence of hyponatremia (plasma sodium \<135 mmol/L)
次要结局
- Change in general well-being(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in daily fluid intake(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in chloride(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Incidence of fractures(Between baseline and visit 3, approximately 3 months)
- Incidence of hospitalization due to any cause(Between baseline and visit 3, approximately 3 months)
- Change in body weight(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in plasma sodium(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Incidence of falls(Between baseline and visit 3, approximately 3 months)
- Change in urinary Prostaglandin- concentration(Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in heart rate(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in Bioelectrical impedance analysis (BIA)(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in potassium(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Change in uric acid(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Change in the expression of proteins involved in sodium and water transport(Between baseline, visit 2 (and visit 2.1 if applicable) and visit 3, approximately 3 months)
- Change in urine sodium(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Change in creatinine(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Change in urea(Between baseline and visit 2 (and visit 2.1 if applicable), approximately 4 weeks)
- Incidence of hyponatremia(Between baseline and visit 3, approximately 3 months)
- Change in systolic and diastolic blood pressure(Between baseline, visit 2 (visit 2.1 if applicable) and visit 3, approximately 3 months)