HyponatremiaNAT-URENCT04552873
Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
A study testing Urea in people with Hyponatremia and Subarachnoid Hemorrhage, run by University Hospital, Grenoble at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyponatremia, Subarachnoid Hemorrhage, SIADH
- What is being tested?
- Urea
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteFrance
- Study dates
- 3 Dec 2020to 1 Aug 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Urea, PLACEBO
- Keywords
- urea, copeptine, hyponatremia, SAH, SIADH
- Medical subject headings
- Hyponatremia, Subarachnoid Hemorrhage, Inappropriate ADH Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UreaDrug
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.
PLACEBOOther
the control group will be treated during 5 days by ergytonyl dose per administration : 5mL
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Urea |
| CONTROL GROUP | Placebo comparator | the control group will be treated during 5 days by ergytonyl dose per administration : 5mL Receives: Other: PLACEBO |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 days
Secondary outcomes (7)
To compare the sodium intake required to correct the natremia.
Measurement of daily sodium intake in each group
Measured: 8 days
To study the mechanism of action of urea
Daily plasma co-peptin levels in each group during treatment and 48 hours after cessation of treatment.
Measured: 48 hours after the end of treatment
To assess the impact of treatment on length of stay
Length of stay in intensive care and/or continuing care unit
Measured: 3 months
To assess the impact of treatment on neurological outcome at 3 months from inclusion
Measurement of modified Rankin score
Measured: 3 months
To assess the adverse effects of treatment
Prevalence of adverse effects of urea (headaches, digestive disorders, etc.)
Measured: 3 months
Persistence of correction of natraemia 48H after cessation of treatment
Variation in natraemia mmol/L measured before introduction of treatment and 48 hours after cessation of treatment
Measured: 48 hours after the end of treatment
To compare the speed of correction of natraemia
Average time taken for natraemia to correct to Na > 135 mmol/L after initiation of treatment.
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2020
- Study start3 Dec 2020
- Primary completion3 Dec 2024
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HyponatremiaStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Comparative study in 2 parallel arms, monocentric, randomized, double blind.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Perrine BOUCHEIX, MD, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04552873
- Sponsor's protocol ID
- 38RC19.189
- Acronym
- NAT-URE
- Status last verified
- Apr 2025
- First submitted
- 10 Sep 2020
- Last updated
- 16 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29051110Mapa 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.
PubMed 26361321Hannon 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.
PubMed 24248182Nakajima 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.
PubMed 28321069Hoorn 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.
PubMed 28174217
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT04552873
- Acronym / sponsor ID
- NAT-URE / 38RC19.189
- Conditions
- Hyponatremia, Subarachnoid Hemorrhage, SIADH
- Keywords
- urea, copeptine, hyponatremia, SAH, SIADH
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 52 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 3 Dec 2020 (actual)
- Primary completion
- 3 Dec 2024 (actual)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 17 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Comparative study in 2 parallel arms, monocentric, randomized, double blind.
| Arm | Type | Receives |
|---|---|---|
| EXPERIMENTAL GROUP | Experimental | Drug: Ureathe 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) |
| CONTROL GROUP | Placebo comparator | Other: PLACEBOthe control group will be treated during 5 days by ergytonyl dose per administration : 5mL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ureathe 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. | Drug | EXPERIMENTAL GROUP |
| PLACEBOthe control group will be treated during 5 days by ergytonyl dose per administration : 5mL | Other | CONTROL GROUP |
Primary outcome
To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage
Time frame: 5 days
Change in blood serum in mmol / L measured before initiation of treatment and on the day of discontinuation of treatment
7 secondary outcomes
To compare the sodium intake required to correct the natremia.
Time frame: 8 days
To study the mechanism of action of urea
Time frame: 48 hours after the end of treatment
To assess the impact of treatment on length of stay
Time frame: 3 months
To assess the impact of treatment on neurological outcome at 3 months from inclusion
Time frame: 3 months
To assess the adverse effects of treatment
Time frame: 3 months
Persistence of correction of natraemia 48H after cessation of treatment
Time frame: 48 hours after the end of treatment
To compare the speed of correction of natraemia
Time frame: 5 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2025.
- Background: PubMed 29051110Hall 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.
- Background: PubMed 26361321Mapa 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.
- Background: PubMed 24248182Hannon 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.
- Background: PubMed 28321069Nakajima 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.
- Background: PubMed 28174217Hoorn 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Perrine BOUCHEIX, MD principal investigator
University Hospital, Grenoble
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Urea in people with Hyponatremia and Subarachnoid Hemorrhage, run by University Hospital, Grenoble at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To demonstrate the effectiveness of urea therapy in correcting persistent hyponatremia despite adequate management during subarachnoid hemorrhage (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04552873, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.