Clinical trial NCT04552873: Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
Official title: Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Hyponatremia
Subarachnoid Hemorrhage
SIADH
Keywords: urea
copeptine
hyponatremia
SAH
SIADH
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2020-09-17
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparative study in 2 parallel arms, monocentric, randomized, double blind.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage
timeFrame: 5 days
Secondary outcomes:
measure: To compare the sodium intake required to correct the natremia.
timeFrame: 8 days
measure: To study the mechanism of action of urea
timeFrame: 48 hours after the end of treatment
measure: To assess the impact of treatment on length of stay
timeFrame: 3 months
measure: To assess the impact of treatment on neurological outcome at 3 months from inclusion
timeFrame: 3 months
measure: To assess the adverse effects of treatment
timeFrame: 3 months
measure: Persistence of correction of natraemia 48H after cessation of treatment
timeFrame: 48 hours after the end of treatment
measure: To compare the speed of correction of natraemia
timeFrame: 5 days
Other outcomes:
Locations:
city: Grenoble
country: France
facility: University Hospital Grenoble
Study officials:
affiliation: University Hospital, Grenoble
name: Perrine BOUCHEIX, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.
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.