Efficacy of Oral Urea Supplementation in Patients With SIAD Not Adequately Controlled With Fluid Restriction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in serum sodium levels
研究概览
简要总结
Hyponatremia due to SIAD is frequently insufficiently corrected by fluid restriction alone, which remains the first-line therapy but is often poorly tolerated. Urea supplementation is recommended as second-line therapy.
This prospective study evaluates the effectiveness of oral urea supplementation in patients with chronic SIAD and persistent hyponatremia despite fluid restriction.
详细描述
Hyponatremia (serum sodium, s-Na <135 mmol/L) is the most common electrolyte disorder in hospitalized patients, with prevalence increasing with length of hospital stay. Among hypotonic euvolemic hyponatremias, the syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause and is characterized by impaired free water excretion. SIAD may result from central nervous system disorders, pulmonary diseases, malignancies, or medications, and remains a diagnosis of exclusion.
When possible, treating the underlying cause can resolve the syndrome; however, in many cases the cause remains unknown and therapeutic options are limited. First-line treatment is fluid restriction, which is often insufficient and difficult to maintain in the long term. AVP receptor antagonists, such as tolvaptan, are effective but expensive and may carry a risk of overly rapid correction of serum sodium.
Second-line therapy recommended by current guidelines is urea supplementation, which has shown safety and efficacy in normalizing serum sodium. However, most available evidence derives from retrospective studies, and prospective data are limited.
This study aims to evaluate the effectiveness of urea supplementation in patients with chronic, mildly symptomatic SIAD-related hyponatremia not adequately controlled by fluid restriction (≤1500 mL/day), and to explore its effects on neuroendocrine adaptation, body fluid composition, and bone metabolism.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Confirmed diagnosis of SIAD established prior to study inclusion, defined as:
- •Plasma sodium concentration <135 mmol/L
- •Plasma osmolality <300 mOsm/kg
- •Urine osmolality >100 mOsm/kg
- •Urine sodium concentration >30 mmol/L
- •Intact adrenal and thyroidal function and no use of diuretics in the last 4 weeks
- •Clinical euvolemia, defined as an absence of signs of hypovolemia (orthostasis, tachycardia, decreased skin turgor, dry mucous membranes) or hypervolemia (edema, ascites)
- •Fulfillment of all diagnostic criteria at baseline (day 0) was not mandatory, as the diagnosis of SIAD had already been established prior to study inclusion based on overall clinical assessment.
- •- Written informed consent obtained
排除标准
- •Chronic hypotonic hyponatremia secondary to another etiology
- •Presence of moderate to severe symptoms attributable to plasma hypotonicity
- •Severe hypotonic hyponatremia (serum sodium <120 mmol/L)
- •Another ongoing drug treatment for hyponatremia (including vaptans and salt tablets)
- •Severe hepatic insufficiency
- •eGFR <45 mL/min/1.73 m²
- •Pregnancy or breastfeeding
- •Known allergy or intolerance to urea
- •Patient refusal or inability to provide written informed consent
研究组 & 干预措施
Urea therapy
Participants will receive oral urea supplementation for 42±4 days, followed by a 10±2-day washout period
干预措施: urea (Dietary Supplement)
结局指标
主要结局
Change in serum sodium levels
时间窗: Baseline, day 1, day 21±4, day 42±4, and 10±2 days post urea discontinuation
Change in serum sodium from baseline to assess the acute and chronic effectiveness of urea therapy in outpatients with SIAD not adequately compensated by fluid restriction (≤1500 mL/day)
次要结局
- Changes in copeptin, NT-proBNP, and MR-proADM levels(Baseline, day 42±4, and 10±2 days post-therapy)
- Bioimpedance adaptation(Baseline, day 42±4, and 10±2 days post-therapy)
- Bone turnover markers(Baseline, day 42±4, and 10±2 days post-therapy)
- Cognitive performance(Baseline and day 42±4)
- Variation in other Serum and Urinary Analytes(Baseline, day 1, day 21±4, day 42±4, and 10±2 days post urea discontinuation)