Pediatric Congestive Heart Failure (CHF) Patients With Volume OverloadPhase 3NCT03255226
Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics Study of Tolvaptan in Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload
A Phase 3 study testing Tolvaptan in people with Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.
Trial summary
To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload Read more about this study
- Who is it for?
- Ages 6 months to 14 years
- Conditions the study is for
- Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteJapan
- Study dates
- 7 Mar 2018to 15 Jul 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload
- Being tested
- Tolvaptan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily.
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | Tolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. Receives: Drug: Tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day after Day 3 at evaluation dose
Secondary outcomes (4)
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
Measured: 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
Measured: 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
Measured: 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
Measured: Day after Day 3 at evaluation dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2017
- Study start7 Mar 2018
- Primary completion11 Jul 2021
- Study completion15 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pediatric Congestive Heart Failure (CHF) Patients With Volume OverloadStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Takehisa Matsumaru, Mr, Study director, Otsuka Pharmaceutical Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03255226
- Sponsor's protocol ID
- 156-102-00123
- Other IDs
- JapicCTI-173674
- Status last verified
- Apr 2024
- First submitted
- 18 Aug 2017
- Last updated
- 23 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03255226
- Acronym / sponsor ID
- 156-102-00123
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 7 Mar 2018 (actual)
- Primary completion
- 11 Jul 2021 (actual)
- Study completion
- 15 Jul 2021 (actual)
- First posted
- 21 Aug 2017 (actual)
- Results
- Posted 23 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the efficacy, safety, and dose and regimen of tolvaptan in pediatric CHF patients with volume overload
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: TolvaptanTolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. |
Who may qualify
- Ages
- 6 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanTolvaptan 1% granules or tolvaptan 15 mg tablet with water once daily. | Drug | Tolvaptan |
Primary outcome
Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline
Time frame: 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.
4 secondary outcomes
Change Rate From Baseline in Daily Urine Volume
Time frame: Baseline, Day1, Day2 and Day3 of administration at evaluation dose
Percent Changes From Baseline in Body Weight (kg)
Time frame: Day after Day 3 at evaluation dose
Improvement Rates of Lower Limb Edema
Time frame: Day after Day 3 at evaluation dose
Improvement Rates of Pulmonary Congestion
Time frame: Day after Day 3 at evaluation dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Takehisa Matsumaru, Mr study director
Otsuka Pharmaceutical Co., Ltd.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan in people with Pediatric Congestive Heart Failure (CHF) Patients With Volume Overload, run by Otsuka Pharmaceutical Co., Ltd. at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentages of Subjects Whose Was Decreased by 1.7% or More Body Weight From Baseline (time frame: Day after Day 3 at evaluation dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.