Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

NCT04552873 | Active Not Recruiting

• 1 other identifier: 38RC19.189
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyponatremia; Subarachnoid Hemorrhage; SIADH

Keywords

urea; copeptine; hyponatremia; SAH; SIADH

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• To compare the sodium intake required to correct the natremia.

  8 days

• To study the mechanism of action of urea

  48 hours after the end of treatment

• To assess the impact of treatment on length of stay

  3 months

• To assess the impact of treatment on neurological outcome at 3 months from inclusion

  3 months

• To assess the adverse effects of treatment

  3 months

Study Arms (2)

EXPERIMENTAL GROUP

EXPERIMENTAL

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

CONTROL GROUP

PLACEBO COMPARATOR

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

Other: PLACEBO

Interventions

Urea DRUG

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.

EXPERIMENTAL GROUP

PLACEBO OTHER

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

CONTROL GROUP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

University Hospital Grenoble

Grenoble, 38043, France

Location

Related Publications (5)

• Hall A, O'Kane R. The Extracranial Consequences of Subarachnoid Hemorrhage. World Neurosurg. 2018 Jan;109:381-392. doi: 10.1016/j.wneu.2017.10.016. Epub 2017 Oct 16.

  PMID: 29051110 BACKGROUND

• Mapa B, Taylor BE, Appelboom G, Bruce EM, Claassen J, Connolly ES Jr. Impact of Hyponatremia on Morbidity, Mortality, and Complications After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review. World Neurosurg. 2016 Jan;85:305-14. doi: 10.1016/j.wneu.2015.08.054. Epub 2015 Sep 7.

  PMID: 26361321 BACKGROUND

• Hannon MJ, Behan LA, O'Brien MM, Tormey W, Ball SG, Javadpour M, Sherlock M, Thompson CJ. Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting. J Clin Endocrinol Metab. 2014 Jan;99(1):291-8. doi: 10.1210/jc.2013-3032. Epub 2013 Dec 20.

  PMID: 24248182 BACKGROUND

• Nakajima H, Okada H, Hirose K, Murakami T, Shiotsu Y, Kadono M, Inoue M, Hasegawa G. Cerebral Salt-wasting Syndrome and Inappropriate Antidiuretic Hormone Syndrome after Subarachnoid Hemorrhaging. Intern Med. 2017;56(6):677-680. doi: 10.2169/internalmedicine.56.6843. Epub 2017 Mar 17.

  PMID: 28321069 BACKGROUND

• Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol. 2017 May;28(5):1340-1349. doi: 10.1681/ASN.2016101139. Epub 2017 Feb 7.

  PMID: 28174217 BACKGROUND

MeSH Terms

Conditions

Hyponatremia; Subarachnoid Hemorrhage; Inappropriate ADH Syndrome

Interventions

Urea

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pituitary Diseases; Hypothalamic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals

Study Officials

• Perrine BOUCHEIX, MD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: September 10, 2020
• First Posted: September 17, 2020
• Study Start: December 3, 2020
• Primary Completion: December 3, 2024
• Study Completion: August 1, 2025
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)