NAT-URE: Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Sponsor

University Hospital, Grenoble (Other)

Overall Status

Recruiting

CT.gov ID

NCT04552873

Collaborator

(none)

Enrollment

Location

Arms

36.9

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hyponatremia Subarachnoid Hemorrhage SIADH	Drug: Urea Other: PLACEBO	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Comparative study in 2 parallel arms, monocentric, randomized, double blind.Comparative study in 2 parallel arms, monocentric, randomized, double blind.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Actual Study Start Date :

Dec 3, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EXPERIMENTAL GROUP 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 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.
Placebo Comparator: CONTROL GROUP the control group will be treated during 5 days by ergytonyl dose per administration : 5mL	Other: PLACEBO the control group will be treated during 5 days by ergytonyl dose per administration : 5mL

Arm

Intervention/Treatment

Experimental: EXPERIMENTAL GROUP

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

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.

Placebo Comparator: CONTROL GROUP

the control group will be treated during 5 days by ergytonyl dose per administration : 5mL

Other: PLACEBO

the control group will be treated during 5 days by ergytonyl dose per administration : 5mL

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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