The purpose of this study is to determine if hospitalized patients with symptomatic hyponatremia treated with tolvaptan are in the hospital for less time than patients treated with fluid restriction. The study will also test if tolvaptan is better than fluid restriction in treating the symptoms of hyponatremia in hospitalized patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
124
15 mg titrated to 30 mg then 60 mg once daily as oral tablet for up to 7 days based on response.
Placebo tablet once daily with prescribed daily fluid intake of 1500 mL, then intensifying to 2 lower volumes of fluid intake for up to 7 days based on response. Since all particpants were blinded to treatment, titration to stricter fluid restriction followed the same algorithm as tolvaptan, increasing both the level of fluid restriction and increasing the placebo "dose"
Length of Hospital Stay (LoS)
LoS was time to clinically ready to be hospital discharged (CRBD) from study treatment initiation, disregarding prolonged hospitalization due solely to social factors.
Time frame: 45 days
Change From Baseline to 48 Hour Post Dose in Clinical Global Impression-Severity (CGI-S) of Hyponatremia Symptoms.
Change from baseline in blinded rater assessed CGI-S at 48 hours post-first dose or at discharge/rescue therapy, if earlier was assessed. The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.
Time frame: Baseline to 48 hours post dose
Change From Baseline to 24 and 72 Hours Post Dose in CGI-S of Hyponatremia Symptoms.
Change in CGI-S of hyponatremia symptoms from pretreatment baseline at 24 and 72 hours post-first dose, or at discharge/rescue therapy if earlier was assessed. The CGI-S is a one-question rating scale which was as follows: "Considering your total clinical experience with hyponatremia symptoms in this particular population, how symptomatic is the patient at this time?" 0=not assessed; 1=normal, not at all symtpmatic; 2=borderline symptomatic; 3=mildly symptomatic; 4=moderately symptomatic; 5=markedly symptomatic; 6=severely symptomatic; 7=among the most severly symptomatic patients.
Time frame: Baseline to 24 and 72 hours post dose
Change From Baseline to 48 Hours Post Dose in Clinical Global Impression - Improvement (CGI-I) Score of Hyponatremia Symptoms.
Change in CGI-I score at 48 hours post-first dose or discharge/rescue therapy, if earlier was assessed. The CGI-I is a one-question rating scale where the participant is asked to rate total improvement whether or not, in their judgment, it is due entirely to trial treatment. Compared to his/her condition at admission to the trial, how much has he/she changed? 0=not assessed; 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Otsuka Investigational Site
Birmingham, Alabama, United States
Otsuka Investigational Site
Birmingham, Alabama, United States
Otsuka Investigational Site
Mobile, Alabama, United States
Otsuka Investigational Site
Azusa, California, United States
Otsuka Investigational Site
Banning, California, United States
Otsuka Investigational Site
Culver City, California, United States
Otsuka Investigational Site
Fountain Valley, California, United States
Otsuka Investigational Site
Los Angeles, California, United States
Otsuka Investigational Site
Los Angeles, California, United States
Otsuka Investigational Site
Northridge, California, United States
...and 46 more locations
Time frame: Baseline to 48 hours post dose
Change From Baseline in Serum Sodium Concentration (24 Hour Area Under the Curve [AUC]).
Average 24 hour AUC of serum sodium concentration change from baseline, from Day 1 Hour 0 up to 72 hours post-first dose was assessed. A serum sodium sample was drawn at pre-treament and 8, 24, 48, and 72 hours post-first dose. Serum sodium was also assessed between 36 and 72 hours after the last dose. Analysis of AUC was for daily average AUC, hence the units or AUC are mEq/L/24 hours.
Time frame: 0 to 72 hours
Time to First 2-point Improvement in CGI-S Score.
CGI-S data up to 72 hours were used to identify 2-point improvements. Please refer to outcome measure 2 for details on the scale. For the analysis of time to first 2-point improvement in CGI-S, CGI-S data up to Hour 72 were used to identify 2-point improvements. Data for participants who received rescue therapy were censored at the time of receiving rescue therapy. For participants who were discharged before Hour 72 without reaching 2-point improvement in CGI-S, data were censored at the time of discharge. Other participants who did not reach the 2-point improvement during the 72 hours also had their data censored at their last CGI-S observations within 72 hours.
Time frame: Up to 72 hours
Percentage of Participants With Clinical Global Impression-Improvement (CGI-I) Score Improved to a Score of 1 or 2.
Percentage of responders (defined as CGI-I score of 1 = very much improved or 2 = much improved) at 48 hours post-first dose, or at discharge/rescue therapy, if earlier. Participants given rescue therapy were given a score of 7.
Time frame: 48 hours post dose
Percentage of Participants Requiring Rescue Therapy for Hyponatremia
Percentage of participants requiring rescue therapy within first 7 days of treatment for hyponatremia.
Time frame: 7 days