Heart FailurePhase 4NCT01439009
Effect of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients
A Phase 4 study testing Tolvaptan in people with Heart Failure, run by Otsuka Pharmaceutical Co., Ltd. at 8 sites in Japan.
Trial summary
One tolvaptan 15 mg tablet or placebo tablet will be orally administered once daily in the morning for up to 14 days to heart failure patients with volume overload that does not show adequate response to other diuretics such as loop diuretics in order to investigate the effect of tolvaptan on the mid- to long-term… Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 8 sitesJapan
- Study dates
- Sep 2011to Mar 2014
- Phase
- Phase 4
- 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 20 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients from whom informed consent has been properly obtained in writing prior to start of the trial
- Patients who have been clinically diagnosed with heart failure
- Patients with any of the following conditions or symptoms: lower limb edema, dyspnea, jugular venous distension, hepatomegaly, pulmonary rales, third heart sound, or pulmonary congestion
- Patients who have been receiving loop diuretics, thiazide diuretics, or anti-aldosterone diuretics
- Male or female patients of age 20 to 85 years inclusive (at time of informed consent)
- Patients who, together with their partner(s), are able to use an appropriate method of contraception until 3 months after final trial drug administration
- Patients who are able to be hospitalized at the trial site for at least 7 days from the start of trial drug administration
Who cannot join
- Patients with a history of hypersensitivity to any ingredient of the drug or to tolvaptan analogues (e.g., mozavaptan hydrochloride)
- Patients with anuria
- Patients who cannot sense thirst or who have difficulty with fluid intake
- Patients with hypernatremia (serum sodium concentration > institutional upper limit of normal) 5) Female patients who are pregnant, possibly pregnant, or nursing
- Patients judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial due to any of the following conditions or symptoms:
- Hyponatremia (serum sodium concentration < 125 mEq/L)
Show all 20Show fewer
- Serious coronary artery disease or cerebrovascular disease
- Hyperkalemia
- Severe renal disorder
- Poorly controlled diabetes mellitus
- Severe hepatic disease
- Impaired urinary excretion due to urinary stenosis, calculus, or tumor
- Cardiac valve disease with significant heart valve stenosis
- Malignant tumor of unfavorable prognosis
- Patients with suspected hypovolemia
- Patients with an implanted circulatory support device
- Patients in whom acute cardiac infarction occurred within 30 days prior to the screening examination
- Patients who participated in any other clinical trial or postmarketing clinical trial within 30 days prior to the date of informed consent for the present trial
- Patients who received tolvaptan within 26 weeks prior to the date of informed consent
- Patients who are otherwise judged by the investigator or sub-investigator to be inappropriate for inclusion in the trial
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Japan8 sites
Study site
Chube Region
Study site
Chushikoku Region
Study site
Hokkaido Region
Study site
Hokuriku Region
Study site
Kansai Region
Study site
Kanto Region
Study site
Kyushu Region
Study site
Tohoku Region
About this study
Official title: A Multi-center,_double-blind,_pararel-group Comparison Trial to Investigate the Effect of Short-term Administration of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients (Phase_4 Study)
One tolvaptan 15 mg tablet or placebo tablet will be orally administered once daily in the morning for up to 14 days to heart failure patients with volume overload that does not show adequate response to other diuretics such as loop diuretics in order to investigate the effect of tolvaptan on the mid- to long-term prognosis of the target population. The efficacy of tolvaptan during the treatment period will also be investigated.
- Conditions
- Heart Failure
- Being tested
- Tolvaptan, Placebo of tolvaptan
- Keywords
- Heart failure, Volume overload, Tolvaptan, loop diuretics
- Medical subject headings
- Heart Failure, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Once-daily oral administration of one tolvaptan 15 mg tablet in the morning
Placebo of tolvaptanDrug
Once-daily oral administration of one placebo tablet in the morning
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | 15 mg Receives: Drug: Tolvaptan |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo of tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cummulative Incidence of Events at Week 26
From start day of IMP administration to final day of follow up period, 1) and 2) below were defined as event
- Death from cardiovascular events
- Worsening of heart failure
- The day of re-hospitalization due to worsening of heart failure
- The day of medication below due to worsening of heart failure Phosphodiesterase III inhibitors (Injection), Catecholamine preparations (Injection), Colforsin preparations (Injection), Diuretics (Injection), Human atrial natriuretic peptide preparations (Injection)：Calperitide (Injection)
Measured: Week 26
Mortality （Number of Death）
Statistical comparison was not done.
Measured: Week26
Body Weight
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Measured: Day15
Number of Subjects Whose Lower Limb Edema Severity Grading Improved by One or More Grade
Of the subjects who had lower limb edema at baseline, the number of subjects whose lower limb edema severity grading. Statistical comparison was not done.
Measured: Day15
Jugular Venous Distension
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Measured: Day15
Change in Liver Size From Baseline
The comparison of the average of amount of change from baseline. Statistical comparison was not done．
Measured: Day15
Pulmonary Rales
Of the subjects who had pulmonary rales at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Measured: Day15
Third Heart Sound
Of the subjects who had third heart sound at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Measured: Day15
Cardiothoracic Ratio
Investigator majored Thoracic length and Cardiac length from chest X-ray. Cardiothoracic Ratio was calculated from Cardiac length/Thoracic length*100. Lowering of Cardiothoracic Ratio suggests recovery from heart congestion.
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Measured: Day15
Pulmonary Congestion
Of the subjects who had pulmonary congestion at baseline, the number of subjects whose pulmonary congestion severity grading showed an improvement of one grade or more (eg, moderate to mild) at completion of treatment. Statistical comparison was not done.
Measured: Day15
Plasma Brain Natriuretic Peptide (BNP) Concentration
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Measured: Day15
Dypnea
Of the subjects who had dyspnoea at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Measured: Day15
Number of Subjects Whose New York Heart Association (NYHA) Classification Improved by One More Grade From Baseline
New York Heart Association (NYHA) Classification is below ClassI：No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
ClassII：Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).
ClassIII：Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.
ClassIV：Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
Measured: The day after last IMP administration and Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionMar 2014
- Study completionMar 2014
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 Heart FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01439009
- Sponsor's protocol ID
- 156-10-005
- Other IDs
- JapicCTI-111621
- Status last verified
- Oct 2019
- First submitted
- 15 Sep 2011
- Last updated
- 22 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center,_double-blind,_pararel-group Comparison Trial to Investigate the Effect of Short-term Administration of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients (Phase_4 Study)
- ClinicalTrials.gov ID
- NCT01439009
- Acronym / sponsor ID
- 156-10-005
- Conditions
- Heart Failure
- Keywords
- Heart failure, Volume overload, Tolvaptan, loop diuretics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 22 Sep 2011 (estimated)
- Results
- Posted 22 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
One tolvaptan 15 mg tablet or placebo tablet will be orally administered once daily in the morning for up to 14 days to heart failure patients with volume overload that does not show adequate response to other diuretics such as loop diuretics in order to investigate the effect of tolvaptan on the mid- to long-term prognosis of the target population. The efficacy of tolvaptan during the treatment period will also be investigated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: Tolvaptan15 mg |
| Placebo | Placebo comparator | Drug: Placebo of tolvaptanPlacebo |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients from whom informed consent has been properly obtained in writing prior to start of the trial
- Patients who have been clinically diagnosed with heart failure
- Patients with any of the following conditions or symptoms: lower limb edema, dyspnea, jugular venous distension, hepatomegaly, pulmonary rales, third heart sound, or pulmonary congestion
- Patients who have been receiving loop diuretics, thiazide diuretics, or anti-aldosterone diuretics
- Male or female patients of age 20 to 85 years inclusive (at time of informed consent)
Key exclusion criteria (20 listed)
- Patients with a history of hypersensitivity to any ingredient of the drug or to tolvaptan analogues (e.g., mozavaptan hydrochloride)
- Patients with anuria
- Patients who cannot sense thirst or who have difficulty with fluid intake
- Patients with hypernatremia (serum sodium concentration > institutional upper limit of normal) 5) Female patients who are pregnant, possibly pregnant, or nursing
- Patients judged by the investigator or subinvestigator to be inappropriate for inclusion in the trial due to any of the following conditions or symptoms:
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 |
|---|---|---|
| TolvaptanOnce-daily oral administration of one tolvaptan 15 mg tablet in the morning | Drug | Tolvaptan |
| Placebo of tolvaptanOnce-daily oral administration of one placebo tablet in the morning | Drug | Placebo |
Primary outcome
Cummulative Incidence of Events at Week 26
Time frame: Week 26
From start day of IMP administration to final day of follow up period, 1) and 2) below were defined as event 1. Death from cardiovascular events 2. Worsening of heart failure * The day of re-hospitalization due to worsening of heart failure * The day of medication below due to worsening of heart failure Phosphodiesterase III inhibitors (Injection), Catecholamine preparations (Injection), Colforsin preparations (Injection), Diuretics (Injection), Human atrial natriuretic peptide preparations (Injection)：Calperitide (Injection)
Mortality （Number of Death）
Time frame: Week26
Statistical comparison was not done.
Body Weight
Time frame: Day15
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Number of Subjects Whose Lower Limb Edema Severity Grading Improved by One or More Grade
Time frame: Day15
Of the subjects who had lower limb edema at baseline, the number of subjects whose lower limb edema severity grading. Statistical comparison was not done.
Jugular Venous Distension
Time frame: Day15
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Change in Liver Size From Baseline
Time frame: Day15
The comparison of the average of amount of change from baseline. Statistical comparison was not done．
Pulmonary Rales
Time frame: Day15
Of the subjects who had pulmonary rales at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Third Heart Sound
Time frame: Day15
Of the subjects who had third heart sound at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Cardiothoracic Ratio
Time frame: Day15
Investigator majored Thoracic length and Cardiac length from chest X-ray. Cardiothoracic Ratio was calculated from Cardiac length/Thoracic length*100. Lowering of Cardiothoracic Ratio suggests recovery from heart congestion. The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Pulmonary Congestion
Time frame: Day15
Of the subjects who had pulmonary congestion at baseline, the number of subjects whose pulmonary congestion severity grading showed an improvement of one grade or more (eg, moderate to mild) at completion of treatment. Statistical comparison was not done.
Plasma Brain Natriuretic Peptide (BNP) Concentration
Time frame: Day15
The comparison of the average of amount of change from baseline. Statistical comparison was not done.
Dypnea
Time frame: Day15
Of the subjects who had dyspnoea at baseline, the number of subjects whose symptom was resolved at completion of treatment. Statistical comparison was not done.
Number of Subjects Whose New York Heart Association (NYHA) Classification Improved by One More Grade From Baseline
Time frame: The day after last IMP administration and Baseline
New York Heart Association (NYHA) Classification is below ClassI：No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). ClassII：Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). ClassIII：Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. ClassIV：Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tolvaptan in people with Heart Failure, run by Otsuka Pharmaceutical Co., Ltd. at 8 sites 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 7 inclusion and 20 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 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 22 Oct 2019). 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?
Cummulative Incidence of Events at Week 26 (time frame: Week 26). The study lists 13 primary outcomes in all. 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 22 Oct 2019.