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Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage (NAT-URE)

Primary Purpose

Hyponatremia, Subarachnoid Hemorrhage, SIADH

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Urea

PLACEBO

About this trial

This is an interventional treatment trial for Hyponatremia focused on measuring urea, copeptine, hyponatremia, SAH, SIADH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

University Hospital GrenobleRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

EXPERIMENTAL GROUP

CONTROL GROUP

Arm Description

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)

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT04552873

First Posted

September 10, 2020

Last Updated

May 17, 2022

Sponsor

University Hospital, Grenoble

1. Study Identification

Unique Protocol Identification Number

NCT04552873

Brief Title

Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Acronym

NAT-URE

Official Title

Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 3, 2020 (Actual)

Primary Completion Date

October 2023 (Anticipated)

Study Completion Date

January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Grenoble

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyponatremia, Subarachnoid Hemorrhage, SIADH

Keywords

urea, copeptine, hyponatremia, SAH, SIADH

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

52 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

EXPERIMENTAL GROUP

Arm Type

Experimental

Arm Description

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)

Arm Title

CONTROL GROUP

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Urea

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

PLACEBO

Intervention Description

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

Primary Outcome Measure Information:

Title

To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage

Description

Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment

Time Frame

5 DAYS

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Perrine BOUCHEIX, MD

Phone

04 76 76 67 29

pboucheix@chu-grenoble.fr

First Name & Middle Initial & Last Name or Official Title & Degree

Anaïs ADOLLE

Phone

04 76 76 67 29

arcpar@chu-grenoble.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Perrine BOUCHEIX, MD

Organizational Affiliation

University Hospital, Grenoble

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Grenoble

City

Grenoble

ZIP/Postal Code

38043

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Perrine BOUCHEIX, MD

First Name & Middle Initial & Last Name & Degree

Anaïs ADOLLE

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29051110

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.

Results Reference

background

PubMed Identifier

26361321

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.

Results Reference

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PubMed Identifier

24248182

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].

Results Reference

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PubMed Identifier

28321069

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.

Results Reference

background

PubMed Identifier

28174217

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.

Results Reference

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Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

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