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Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial (DASSOH)

Primary Purpose

Hyponatremia

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
DDAVP
Standard hyponatremia treatment
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyponatremia

Eligibility Criteria

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

Inclusion Criteria: Adults ( ≥18 years) Current admission in ICU Severe hyponatremia defined by SNa <120 mmol/L in the presence of neurological symptoms (seizures, stupor defined as Glasgow score < 12, or signs of brain herniation) or by SNa <115 mmol/L Normal or decreased extracellular fluid volume Exclusion Criteria: Obvious increase of extracellular fluid volume (cirrhosis with ascites, congestive heart failure, nephrotic syndrome); Previous DDAVP or hypertonic fluid administration for the current episode of severe hyponatremia SNa increased by 5 mmol or more between admission at hospital and randomisation (H0) Known contraindication to DDAVP Allergy Syndrome of inappropriate antidiuretic hormone secretion (SIADH) History of unstable angina and/or known or suspected heart failure. Willebrand disease type 2b (due to risk of thrombocytopenia) Severe previous neurologic disability (Glasgow Outcome Scale < 3) Diabetes insipidus receiving DDAVP treatment Moribund state (patient likely to die within 24h) Need for invasive mechanic ventilation Limitation of life support (comfort care applied only) at the time of screening Enrolment to another interventional study on hyponatremia care/management Pregnancy or breastfeeding Subject deprived of freedom, subject under a legal protective measure No affiliation to any health insurance system Refusal to participate to the study (patient or legal representative or family member or close relative if present)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    DDAVP

    Standard hyponatremia treatment

    Arm Description

    DDAVP 4µg/ml IV Additional doses may be administrated every 6h for a maximum of 48h - Standard hyponatremia treatment : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic

    Standard hyponatremia treatment alone : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic

    Outcomes

    Primary Outcome Measures

    reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization
    proportion of patients with SNa level overcorrection : any risk factor: SNa increase > 6 mmol/L in less than H24, or >12 mmol/L in less than H48. Without risk factor: SNa increase > 10 mmol/L in less than H24, or > 18 mmol/L in less than H48

    Secondary Outcome Measures

    the reversal of acute neurological symptoms in patients with neurological symptoms at inclusion
    proportion of patients with neurological symptoms at inclusion and who subsequently have a normal Glasgow Coma Scale at H6
    ICU and hospital length of stay
    length of ICU and hospital stay
    survival
    time to death after inclusion
    the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria
    proportion of patients with the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria at day 15 (or earlier if clinically justified)
    the occurrence of any (pontine or extrapontine) osmotic demyelination as assessed by brain MRI
    proportion of patients with any (pontine or extrapontine), symptomatic or not, osmotic demyelination as assessed by brain MRI at day 15 (or earlier if clinically justified)
    on the percentage of patients with neurological symptoms at inclusion and reaching the initial goal of rapid partial pre-defined correction of SNa level
    proportion of patients with neurological symptoms with an increase of 5.0 mmol/L or more of SNa from inclusion to H6
    the urine output between H0 and H6
    urine output between H0 and H6
    the urine output between H6 and H12
    urine output between H6 and H12
    the urine output between H12 and H24
    urine output between H12 and H24
    the urine output between H24 and H48
    urine output between H24 and H48
    the urine osmolality between H0 and H6
    urine osmolality between H0 and H6
    the urine osmolality between H6 and H12
    urine osmolality between H6 and H12
    the urine osmolality between H12 and H24
    urine osmolality between H12 and H24
    the urine osmolality between H24 and H48
    urine osmolality between H24 and H48
    SNa level correction rate between H0 and H24
    slope of the SNa increase between H0 and H24
    SNa level correction rate between H0 and H48
    slope of the SNa increase between H0 and H48
    the maximal change of SNa level between H0 and H24
    maximum change of SNa from baseline between H0 and H24
    the maximal change of SNa level between H0 and H48
    maximum change of SNa from baseline between H0 and H48
    amount of hypotonic fluids administration
    total amount of intravenous hypotonic fluids administered between H0 and H24
    amount of hypotonic fluids administration
    total amount of intravenous hypotonic fluids administered between H0 and H48
    amount of sodium and potassium administered between H0 and H24
    total amount of sodium and potassium administered between H0 and H24
    amount of sodium and potassium administered between H0 and H48
    total amount of sodium and potassium administered between H0 and H48
    the occurrence of any new neurological sign in relation with hyponatremia in patients with a normal neurological exam at inclusion or on the reappearance of any neurological sign in relation with hyponatremia after inclusion
    proportion of patients with seizures, stupor or sign of brain herniation appearing or reappearing after inclusion
    the occurrence of excessive re-lowering of sodium
    Occurrence of a reduction of SNa of 5.0 mmol/L or more from inclusion between H0 and H48

    Full Information

    First Posted
    August 28, 2023
    Last Updated
    August 28, 2023
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06020495
    Brief Title
    Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial
    Acronym
    DASSOH
    Official Title
    Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    January 1, 2024 (Anticipated)
    Primary Completion Date
    January 31, 2026 (Anticipated)
    Study Completion Date
    March 31, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris

    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
    ICU patients with severe hyponatremia and a high risk of rapid SNa overcorrection.
    Detailed Description
    Multicentre, prospective, open-label randomized controlled superiority trial with stratification on the presence of neurological symptoms at inclusion and on the presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse, malnutrition, serum potassium < 3.0 mmol/L). Patients in ICU with severe hyponatremia defined by SNa < 115 mmol/L or SNa < 120 mmol/L in the presence of neurological symptoms (convulsions, stupor defined by a Glasgow score <12 or signs of brain herniation) and a normal or decreased extracellular fluid volume will be included. After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by the presence of neurological symptoms at inclusion (seizures, stupor defined as Glasgow score <12 or signs of brain herniation) and on the presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse [defined according to World Health Organization definition], malnutrition [BMI<20.5 or weight loss >5% in 3 months], serum potassium < 3.0 mmol/L), through a centralized 24-hour Internet service (CleanWEB™), to receive standard hyponatremic treatment alone or standard hyponatremic treatment and DDAVP 4 μg/ml IV, after randomisation and for a total duration of 48 hours. Since administration of DDAVP leads to an important decrease in urine output and increase in urine osmolarity which are clinically obvious very rapidly, a single or double blind trial is not appropriate. However, all investigators will be unaware of aggregate outcomes during the study and brain MRI imaging will be performed and analyzed blinded to the randomization group

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    Multicentre, prospective, open-label randomized controlled superiority trial with stratification on the presence of neurological symptoms at inclusion and on the presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse, malnutrition, serum potassium < 3.0 mmol/L).
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    260 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    DDAVP
    Arm Type
    Experimental
    Arm Description
    DDAVP 4µg/ml IV Additional doses may be administrated every 6h for a maximum of 48h - Standard hyponatremia treatment : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic
    Arm Title
    Standard hyponatremia treatment
    Arm Type
    Active Comparator
    Arm Description
    Standard hyponatremia treatment alone : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic
    Intervention Type
    Drug
    Intervention Name(s)
    DDAVP
    Intervention Description
    Posology: 4µg in 2ml IV solution Route of administration: Intravenous Duration of treatment: 48h maximum (additional doses every 6h)
    Intervention Type
    Drug
    Intervention Name(s)
    Standard hyponatremia treatment
    Intervention Description
    Standard hyponatremia treatment alone : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic
    Primary Outcome Measure Information:
    Title
    reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization
    Description
    proportion of patients with SNa level overcorrection : any risk factor: SNa increase > 6 mmol/L in less than H24, or >12 mmol/L in less than H48. Without risk factor: SNa increase > 10 mmol/L in less than H24, or > 18 mmol/L in less than H48
    Time Frame
    48 hours after the randomization
    Secondary Outcome Measure Information:
    Title
    the reversal of acute neurological symptoms in patients with neurological symptoms at inclusion
    Description
    proportion of patients with neurological symptoms at inclusion and who subsequently have a normal Glasgow Coma Scale at H6
    Time Frame
    6 hours after the randomization
    Title
    ICU and hospital length of stay
    Description
    length of ICU and hospital stay
    Time Frame
    ICU or hospital discharge
    Title
    survival
    Description
    time to death after inclusion
    Time Frame
    death after randomization
    Title
    the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria
    Description
    proportion of patients with the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria at day 15 (or earlier if clinically justified)
    Time Frame
    15 days after randomization
    Title
    the occurrence of any (pontine or extrapontine) osmotic demyelination as assessed by brain MRI
    Description
    proportion of patients with any (pontine or extrapontine), symptomatic or not, osmotic demyelination as assessed by brain MRI at day 15 (or earlier if clinically justified)
    Time Frame
    15 days after randomization
    Title
    on the percentage of patients with neurological symptoms at inclusion and reaching the initial goal of rapid partial pre-defined correction of SNa level
    Description
    proportion of patients with neurological symptoms with an increase of 5.0 mmol/L or more of SNa from inclusion to H6
    Time Frame
    6 hours after the randomization
    Title
    the urine output between H0 and H6
    Description
    urine output between H0 and H6
    Time Frame
    6 hours after the randomization
    Title
    the urine output between H6 and H12
    Description
    urine output between H6 and H12
    Time Frame
    12 hours after the randomization
    Title
    the urine output between H12 and H24
    Description
    urine output between H12 and H24
    Time Frame
    24 hours after the randomization
    Title
    the urine output between H24 and H48
    Description
    urine output between H24 and H48
    Time Frame
    48 hours after the randomization
    Title
    the urine osmolality between H0 and H6
    Description
    urine osmolality between H0 and H6
    Time Frame
    6 hours after the randomization
    Title
    the urine osmolality between H6 and H12
    Description
    urine osmolality between H6 and H12
    Time Frame
    12 hours after the randomization
    Title
    the urine osmolality between H12 and H24
    Description
    urine osmolality between H12 and H24
    Time Frame
    24 hours after the randomization
    Title
    the urine osmolality between H24 and H48
    Description
    urine osmolality between H24 and H48
    Time Frame
    48 hours after the randomization
    Title
    SNa level correction rate between H0 and H24
    Description
    slope of the SNa increase between H0 and H24
    Time Frame
    24 hours after the randomization
    Title
    SNa level correction rate between H0 and H48
    Description
    slope of the SNa increase between H0 and H48
    Time Frame
    48 hours after the randomization
    Title
    the maximal change of SNa level between H0 and H24
    Description
    maximum change of SNa from baseline between H0 and H24
    Time Frame
    24 hours after the randomization
    Title
    the maximal change of SNa level between H0 and H48
    Description
    maximum change of SNa from baseline between H0 and H48
    Time Frame
    48 hours after the randomization
    Title
    amount of hypotonic fluids administration
    Description
    total amount of intravenous hypotonic fluids administered between H0 and H24
    Time Frame
    24 hours after the randomization
    Title
    amount of hypotonic fluids administration
    Description
    total amount of intravenous hypotonic fluids administered between H0 and H48
    Time Frame
    48 hours after the randomization
    Title
    amount of sodium and potassium administered between H0 and H24
    Description
    total amount of sodium and potassium administered between H0 and H24
    Time Frame
    24 hours after the randomization
    Title
    amount of sodium and potassium administered between H0 and H48
    Description
    total amount of sodium and potassium administered between H0 and H48
    Time Frame
    48 hours after the randomization
    Title
    the occurrence of any new neurological sign in relation with hyponatremia in patients with a normal neurological exam at inclusion or on the reappearance of any neurological sign in relation with hyponatremia after inclusion
    Description
    proportion of patients with seizures, stupor or sign of brain herniation appearing or reappearing after inclusion
    Time Frame
    28 days after randomization
    Title
    the occurrence of excessive re-lowering of sodium
    Description
    Occurrence of a reduction of SNa of 5.0 mmol/L or more from inclusion between H0 and H48
    Time Frame
    48 hours after the randomization

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Adults ( ≥18 years) Current admission in ICU Severe hyponatremia defined by SNa <120 mmol/L in the presence of neurological symptoms (seizures, stupor defined as Glasgow score < 12, or signs of brain herniation) or by SNa <115 mmol/L Normal or decreased extracellular fluid volume Exclusion Criteria: Obvious increase of extracellular fluid volume (cirrhosis with ascites, congestive heart failure, nephrotic syndrome); Previous DDAVP or hypertonic fluid administration for the current episode of severe hyponatremia SNa increased by 5 mmol or more between admission at hospital and randomisation (H0) Known contraindication to DDAVP Allergy Syndrome of inappropriate antidiuretic hormone secretion (SIADH) History of unstable angina and/or known or suspected heart failure. Willebrand disease type 2b (due to risk of thrombocytopenia) Severe previous neurologic disability (Glasgow Outcome Scale < 3) Diabetes insipidus receiving DDAVP treatment Moribund state (patient likely to die within 24h) Need for invasive mechanic ventilation Limitation of life support (comfort care applied only) at the time of screening Enrolment to another interventional study on hyponatremia care/management Pregnancy or breastfeeding Subject deprived of freedom, subject under a legal protective measure No affiliation to any health insurance system Refusal to participate to the study (patient or legal representative or family member or close relative if present)
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    GAUDRY Stéphane
    Phone
    01.48.95.55.55
    Email
    stephane.gaudry@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    DECHANET Aline
    Phone
    01 40 25 78 30
    Email
    aline.dechanet@aphp.fr

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial

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