A Phase 3 interventional study of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload, sponsored by Otsuka Pharmaceutical Co., Ltd.. Completed at 1 site in Japan. Open to participants aged 6 Months to 14 Years. Per ClinicalTrials.gov, last updated 2024-08-23.
Sponsored by Otsuka Pharmaceutical Co., Ltd. · Phase 3, Interventional, and Treatment
To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload
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
others
Exclusion Criteria:
Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Drug: Tolvaptan
Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline
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.
Time frame: Day after Day 3 at evaluation dose
Change Rate From Baseline in Daily Urine Volume
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
Time frame: Baseline, Day1, Day2 and Day3 of administration at evaluation dose
Percent Changes From Baseline in Body Weight (kg)
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
Time frame: Day after Day 3 at evaluation dose
Improvement Rates of Lower Limb Edema
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
Time frame: Day after Day 3 at evaluation dose
Improvement Rates of Pulmonary Congestion
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
Time frame: Day after Day 3 at evaluation dose
| Milestone | Tolvaptan |
|---|---|
| Started | 60 |
| Completed | 46 |
| Not completed | 14 |
| Withdrew: Adverse event | 2 |
| Withdrew: Physician decision | 3 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Serum or blood sodium increased | 4 |
| Withdrew: Serum or blood potassium increased | 4 |
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.
| percentage of participants | Tolvaptan |
|---|---|
| Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline | 22.8 (12.7 to 35.8) |
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
| percentage of urine volume (mL) | Tolvaptan |
|---|---|
| Day 1 | 53.1 ± 52.9 |
| Day 2 | 47.8 ± 43.3 |
| Day 3 | 45.8 ± 29.3 |
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
| percentage of body weight (kg) | Tolvaptan |
|---|---|
| Percent Changes From Baseline in Body Weight (kg) | -0.371 ± 2.470 |
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
| percentage of participants | Tolvaptan |
|---|---|
| Improvement Rates of Lower Limb Edema | 68.6 (50.7 to 83.1) |
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
| percentage of participants | Tolvaptan |
|---|---|
| Improvement Rates of Pulmonary Congestion | 51.6 (33.1 to 69.8) |
Collected over Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration up to 16 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Tolvaptan | 0/60 (0%) | 1/60 (1.7%) | 25/60 (41.7%) |
| Event | Tolvaptan |
|---|---|
| Cardiac failure chronicCardiac disorders | 1/60 |
| Event | Tolvaptan |
|---|---|
| ThirstGeneral disorders | 4/60 |
| AnaemiaBlood and lymphatic system disorders | 2/60 |
| ConstipationGastrointestinal disorders | 2/60 |
| Dry mouthGastrointestinal disorders | 2/60 |
| VomitngGastrointestinal disorders | 2/60 |
| PyrexiaGeneral disorders | 2/60 |
| HyperkalaemiaMetabolism and nutrition disorders | 2/60 |
| NeutropeniaBlood and lymphatic system disorders | 1/60 |
| Cardiovascular insufficiencyCardiac disorders | 1/60 |
| Erythema of eyelidEye disorders | 1/60 |
The FAS included 59 of 60 subjects (98.3%) who received the IMP. One subject was excluded from the FAS because the subject received the IMP at least once, and discontinued the trial before the daily urine volume data on Day 1 were obtained.
| Age, Continuous(years) | Tolvaptan |
|---|---|
| Mean | 5.44 ± 5.03 |
| Age, Customized(Participants) | Tolvaptan |
|---|---|
| Age group — 6 months to less than 2 years | 20 |
| Age group — 2 years to less than 7 years | 16 |
| Age group — 7 years to less than 15 years | 23 |
| Sex: Female, Male(Participants) | Tolvaptan |
|---|---|
| Female | 28 |
| Male | 31 |
| Race/Ethnicity, Customized(Participants) | Tolvaptan |
|---|---|
| Asian | 59 |
| Region of Enrollment(participants) | Tolvaptan |
|---|---|
| Japan | 59 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
Supporting information: Study protocol, Sap
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Otsuka Pharmaceutical Co., Ltd.