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
Sponsored by
About this trial
This is an interventional treatment trial for Hyponatremia focused on measuring urea, copeptine, hyponatremia, SAH, SIADH
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
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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
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
No
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
Email
pboucheix@chu-grenoble.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Anaïs ADOLLE
Phone
04 76 76 67 29
Email
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
No
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
background
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
background
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
background
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Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
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