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

Phase 3

Completed

• Conditions: Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload
• Interventions: Drug: Tolvaptan

• Registration Number: NCT03255226
• Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief Summary

To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-18
• Study First Submitted QC: 2017-08-18
• Study First Posted: 2017-08-21
• Study Start: 2018-03-07
• Primary Completion: 2021-07-11
• Study Completion: 2021-07-15
• Results First Submitted: 2022-06-27
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-02
• Last Update Submitted: 2024-04-02
• Results First Posted: 2024-08-23
• Last Update Posted: 2024-08-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tolvaptan	Tolvaptan	Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.

Primary Outcome Measures

Name	Time	Method
Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline	Day after Day 3 at evaluation dose	The primary endpoint of this trial was the percentage of subjects whose body weight on the day after the third day of treatment with tolvaptan at the evaluation dose (the third day of administration at the evaluation dose) was decreased by 1.7% or more from the weight measured before breakfast (baseline) on the first day of the treatment period (the initial tolvaptan administration day), under the condition that the mean daily urine volume for the 3 days of treatment with tolvaptan at the evaluation dose was higher than the daily urine volume for the pretreatment observation period.; The percentage of subjects as well as the exact 95% confidence interval (CI) based on binomial distribution were calculated.

Secondary Outcome Measures

Name	Time	Method
Improvement Rates of Pulmonary Congestion	Day after Day 3 at evaluation dose	The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration.; Improvement category is a 4-point scale below: * Markedly improved; * Improved; * Unchanged; * Deteriorated
Improvement Rates of Lower Limb Edema	Day after Day 3 at evaluation dose	The improvement rate was defined as the percentage of subjects in whom a symptom was present at baseline and then markedly improved or improved after IMP administration.; Improvement category is a 4-point scale below: * Markedly improved; * Improved; * Unchanged; * Deteriorated
Change Rate From Baseline in Daily Urine Volume	Baseline, Day1, Day2 and Day3 of administration at evaluation dose	Daily urine volume was measured for the time interval starting at urination (an instruction to urinate) after breakfast and ending at complete urination immediately before administration on the following day.; Baseline was 100% and the change rate was calculated like this. Percent change (%) = (\[daily urine volume on the Day1, Day2 and Day3 of the tolvaptan at the evaluation dose\] - \[daily urine volume on baseline\] ) / \[daily urine volume on baseline\] ×100
Percent Changes From Baseline in Body Weight (kg)	Day after Day 3 at evaluation dose	Percent change from baseline in body weight (kg) on the day after the third day of treatment with tolvaptan at the evaluation dose was evaluated.; For body weight measured on the day after the third day of administration at the evaluation dose, their percent changes from baseline (before the start of tolvaptan administration on the first day of the treatment period) mean and standard deviation (SD) were calculated.; Baseline was 100% and the change rate was alculated like this. Percent change (%) = (\[body weight on the day after the third day of treatment with tolvaptan at the evaluation dose\] - \[body weight on baseline\] ) / \[body weight on baseline\] ×100