Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload

Study Overview
=================
Brief Summary
-----------------
To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload

Official Title
-----------------
A Multicenter, Open-labeled, Dose-defining Trial to Investigate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload

Conditions
-----------------
Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload

Intervention / Treatment
-----------------
* Drug: Tolvaptan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with volume overload despite having received any of the following diuretic therapies in whom sufficient effects cannot be expected even if the dose of the diuretics is increased or in whom the investigator or subinvestigator judges that increasing the dose of the diuretics is difficult due to concerns regarding electrolyte abnormalities or other side effects Furosemide (oral administration) ≥0.5 mg/kg/day. Azosemide 30 mg and torasemide 4 mg will be calculated as equivalent to furosemide 20 mg. Hydrochlorothiazide ≥2 mg/kg/day Trichlormethiazide ≥0.05 mg/kg/day Spironolactone ≥ 1 mg/kg/day Patients capable of complaining of thirst. Patients unable to complain of thirst due to their young age can also be enrolled in the trial if strict management of fluid intake and excretion is conducted. However, even if such fluid management is possible, the patients in whom the investigator or subinvestigator judges that tolvaptan cannot be safely administered are to be excluded Patients who can be hospitalized from at least 3 days before start of tolvaptan administration until 2 days after the final administration. others Exclusion Criteria: Patients whose volume overload status shows improvement during the screening period or pretreatment observation period Patients who are unable to drink fluid (including patients who are unable to sense thirst) Patients whose circulatory blood flow is suspected to be decreased Patients with an assisted circulation apparatus Patients with hypernatremia (serum or blood sodium concentration exceeding 145 mEq/L) others

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 14 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tolvaptan<br>Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. | Drug: Tolvaptan<br>* Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of subject whom the body weight is decreased from baseline | Ratio of subject whom the body weight is decreased by 1.7% or more from the baseline. | -day1, day4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change the amount of daily urine volume from baseline |  | -day1 to day9 |