Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Not Applicable

Active, not recruiting

• Conditions: Hyponatremia; Subarachnoid Hemorrhage; SIADH
• Interventions: Other: PLACEBO; Drug: Urea

• Registration Number: NCT04552873
• Lead Sponsor: University Hospital, Grenoble

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-10
• Study First Submitted QC: 2020-09-10
• Study First Posted: 2020-09-17
• Study Start: 2020-12-03
• Primary Completion: 2024-12-03
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-11
• Last Update Posted: 2025-04-16
• Study Completion: 2025-08-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 52

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CONTROL GROUP	PLACEBO	the control group will be treated during 5 days by ergytonyl dose per administration : 5mL
EXPERIMENTAL GROUP	Urea	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)

Primary Outcome Measures

Name	Time	Method
To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage	5 days	Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment

Secondary Outcome Measures

Name	Time	Method
To compare the sodium intake required to correct the natremia.	8 days	Measurement of daily sodium intake in each group
To assess the impact of treatment on length of stay	3 months	Length of stay in intensive care and/or continuing care unit
To assess the impact of treatment on neurological outcome at 3 months from inclusion	3 months	Measurement of modified Rankin score
To study the mechanism of action of urea	48 hours after the end of treatment	Daily plasma co-peptin levels in each group during treatment and 48 hours after cessation of treatment.
To assess the adverse effects of treatment	3 months	Prevalence of adverse effects of urea (headaches, digestive disorders, etc.)
Persistence of correction of natraemia 48H after cessation of treatment	48 hours after the end of treatment	Variation in natraemia mmol/L measured before introduction of treatment and 48 hours after cessation of treatment
To compare the speed of correction of natraemia	5 days	Average time taken for natraemia to correct to Na \> 135 mmol/L after initiation of treatment.

Trial Locations

Locations (1)

University Hospital Grenoble; 🇫🇷 Grenoble, France