Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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Hyponatremia is defined as a plasma sodium concentration below 135 mmol / L. This is a common occurrence (20-50%) during subarachnoid hemorrhage (SAH). Its appearance is often associated with vasospasm. It is associated with an increase in morbidity and mortality linked to induced neurological disorders. Hyponatremia is caused by two etiologies: the syndrome of inappropriate secretion of anti-diuretic hormone (SIADH), and the cerebral salt wasting syndrome, CSWS. Theoretically, these two entities are differentiated by the patient's volemia; in practice, this parameter is difficult to measure. In addition, the correction of hyponatremia is diametrically opposed according to its mechanism: water restriction in the case of SIADH, sodium intake in the event of CSWS. Urea is offered as a second-line treatment in the event of treatment failure to correct hyponatremia. However, the efficacy of this treatment is based on small, observational, retrospective studies. Moreover, the mechanism of action of urea remains poorly understood: it could be a hyperosmolar effect or passive renal reabsorption of sodium.

Official Title
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Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Conditions
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Hyponatremia, Subarachnoid Hemorrhage, SIADH

Intervention / Treatment
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* Drug: Urea
* Other: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged at least 18 years old Non-traumatic HSA Hyponatremia defined by a natremia less than 135 mmol / L and a high natriuresis, greater than 250 mmol / L despite well-managed saline intakes Exclusion Criteria: Severe cardiac decompensation (LVEF <30%) Severe hepatic cirrhosis (PT <30%, ascites), known severe renal failure (GFR <30mL / min / 1.73m²) Blood urea> 25 mmol / L in the basal state Osmotherapy and diuretics in the last 48 hours Ongoing treatment with systemic corticosteroids Persons referred to in Articles L1121-5 to L1121-8 of the CSP corresponding to all protected persons: pregnant woman, parturient, nursing mother, person deprived of liberty by judicial or administrative decision, person subject to a legal protection measure. Patient not affiliated to a social security scheme Known hypersensitivity to any of the components of ergytonyl Contraindications to ergytonyl: taking curative anticoagulants, previously known and treated diabetic patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Comparative study in 2 parallel arms, monocentric, randomized, double blind.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXPERIMENTAL GROUP<br>the experimental group will be treated during 5 days by urea dose per administration : 1g / kg / 24 hours in 2 or 3 doses morning, noon and evening (dose adjustment of urea according to weight) | Drug: Urea<br>* the experimental group will be treated during 5 days by urea dose per administration : 1g / kg / 24 hours in 2 or 3 doses morning, noon and evening (dose adjustment of urea according to weight) If hyponatremia persists beyond D8 after initiation of the study treatment (urea or placebo), that is to say after the date of the collection of the primary endpoint, it will be possible to introduce corticosteroids (fludrocortisone or others). These treatments will be collated. If during patient monitoring the serum sodium exceeds 145 mmol / L, treatment should no longer be administered.<br>|
| Placebo Comparator: CONTROL GROUP<br>the control group will be treated during 5 days by ergytonyl dose per administration : 5mL | Other: PLACEBO<br>* the control group will be treated during 5 days by ergytonyl dose per administration : 5mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage | Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment | 5 DAYS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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urea, copeptine, hyponatremia, SAH, SIADH