Hyponatremia | Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia
Hyponatremia research study
What is the primary objective of this study?
The purpose of this trial is to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent subjects with euvolemic or hypervolemic hyponatremia.
Who is eligible to participate?
Inclusion: - Male and female subjects ≥ 4 weeks (or ≥44 weeks adjusted gestational age) to <18 years old - Subjects hospitalized with euvolemic or hypervolemic hyponatremia resistant to initial standard background therapy - Persistent euvolemic or hypervolemic hyponatremia defined as being documented as <130 mEq/L and present for at least 48 h, evidenced by at least 2 serum sodium assessments (12 h apart) - Ability to maintain adequate fluid intake (orally or IV) - Ability to take oral medications - Ability to comply with all requirements of the trial - Completion of the trial specific informed consent/assent as age appropriate - Ability to commit to remain fully abstinent or practice double-barrier birth control as required by the trial. Exclusion: - Evidence of hypovolemia or intravascular volume depletion - Serum sodium < 120 mEq/L - Use of potent CYP3A4 inhibitors in subjects < 12 kg or moderate CYP3A4 inhibitors in subjects < 6 kg - Lacks free access to water or without ICU-level fluid monitoring and management - History or current diagnosis of nephrotic syndrome - Transient hyponatremia likely to resolve - Hyperkalemia - eGFR < 30 mL/min/1.73 m² - Acute kidney injury - Severe or acute neurological symptoms requiring other intervention - Prior treatment for hyponatremia with hypertonic saline within 8 hours of qualifying serum sodium assessments; Urea, lithium, demeclocycline, conivaptan, or tolvaptan within 4 days of qualifying serum sodium assessments; any other treatments for the purpose of increasing serum sodium concurrent with dosing of trial medication. - Anuria or urinary outflow obstruction, unless subject is/can be catheterized - History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives - Psychogenic polydipsia - Uncontrolled diabetes mellitus (defined as fasting glucose > 300mg/dL). - Screening liver function values > 3 x ULN - Subjects who have cirrhosis and meet any of the following conditions: a major GI bleed within the past 6 months, evidence of active bleeding, platelet count < 50,000 /μL, or use of concomitant medications known to increase bleeding risk - Hyponatremia due to the result of any medication that can safely be withdrawn or that is most appropriately corrected by alternative therapies - History of drug or medication abuse within 3 months prior to screening or current alcohol abuse - Subjects who require suspension formulation and have a Hereditary Fructose Intolerance - Has hyponatremia that is more appropriately corrected by alternative therapies - Is pregnant or currently breastfeeding - Has any medical condition that could interfere with evaluation of trial objectives or subject safety - Has participated in another investigational drug trial in the last 30 days - Weighs < 3 kg - Unable to swallow tablets, if suspension unavailable - Is deemed unsuitable for trial participation in the opinion of the PI
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Tolvaptan Early WithdrawalAll subjects will initially receive tolvaptan once daily for the first 2 days. A third day of treatment is permitted if a subject has not reached the desired sodium target improvement per the investigator's judgment. At the end of Day 2 (or Day 3), responders (subjects who achieve an increase in serum sodium by ≥ 4 mmol/L) are randomized to either the Early or Late Withdrawal Group. Nonresponders can continue treatment with tolvaptan for an additional 2 days. Discontinue tolvaptan treatment immediately after randomization. All subjects observed to 14 days post randomization.
Tolvaptan Late WithdrawalAll subjects will initially receive tolvaptan once daily for the first 2 days. A third day of treatment is permitted if a subject has not reached the desired sodium target improvement per the investigator's judgment. At the end of Day 2 (or Day 3), responders (subjects who achieve an increase in serum sodium by ≥ 4 mmol/L) are randomized to either the Early or Late Withdrawal Group in Treatment Phase B. Nonresponders can continue treatment with tolvaptan for an additional 2 days. Continue treatment for 2 additional days. All subjects observed to 14 days post randomization.
Start Date: November 2014
Completed Date: July 2017
Phase: Phase 3
Primary Outcome: Change in serum sodium concentration.
Secondary Outcome: Change in serum sodium concentration.
Study sponsors, principal investigator, and references
Principal Investigator: Ann Dandurand, MD
Collaborator: INC Research