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Active, Not Recruiting

NCT Number: NCT04552873

Urea Therapy for Hyponatremia in Subarachnoid Hemorrhage

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Hyponatremia Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Endocrine System Diseases Hemorrhage Hypothalamic Diseases Inappropriate ADH Syndrome Intracranial Hemorrhages Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Pituitary Diseases SIADH Subarachnoid Hemorrhage Vascular Diseases Water-Electrolyte Imbalance

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Hospital Grenoble

Grenoble, 38043, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

urea

Drug

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.

Placebo

Other

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

Primary outcomes

  1. 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

Secondary outcomes

  1. To compare the sodium intake required to correct the natremia.

    Time frame: 8 days

    Measurement of daily sodium intake in each group

  2. To study the mechanism of action of urea

    Time frame: 48 hours after the end of treatment

    Daily plasma co-peptin levels in each group during treatment and 48 hours after cessation of treatment.

  3. To assess the impact of treatment on length of stay

    Time frame: 3 months

    Length of stay in intensive care and/or continuing care unit

  4. To assess the impact of treatment on neurological outcome at 3 months from inclusion

    Time frame: 3 months

    Measurement of modified Rankin score

  5. To assess the adverse effects of treatment

    Time frame: 3 months

    Prevalence of adverse effects of urea (headaches, digestive disorders, etc.)

  6. Persistence of correction of natraemia 48H after cessation of treatment

    Time frame: 48 hours after the end of treatment

    Variation in natraemia mmol/L measured before introduction of treatment and 48 hours after cessation of treatment

  7. To compare the speed of correction of natraemia

    Time frame: 5 days

    Average time taken for natraemia to correct to Na > 135 mmol/L after initiation of treatment.

Sponsors and collaborators

Lead sponsor

University Hospital, Grenoble

Other

Registry information

Acronym: NAT-URE

Important dates

Study start
2020
Primary completion
2024
Study completion
2025
First posted
Sep 17, 2020
Registry last updated
Apr 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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