Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Subarachnoid Hemorrhage Clinical Trial

— NAT-URE  

Official title:

Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04552873
• Other study ID #: 38RC19.189
• Status: Recruiting
• Phase: N/A
• Start date: December 3, 2020
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: University Hospital, Grenoble
• Contact: Perrine BOUCHEIX, MD
• Phone: 04 76 76 67 29
• Email: pboucheix[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 52
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemorrhage
• Hyponatremia
• SIADH
• Subarachnoid Hemorrhage

Intervention

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.

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

Locations

Country	Name	City	State
France	University Hospital Grenoble	Grenoble

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & 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. — View Citation

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. Erratum In: J Clin Endocrinol Metab. 2014 Mar;99(3):1096. Javadpur, M [corrected to Javadpour, M]. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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