Effect of Tolvaptan on Mid- to Long-term Prognosis of Heart Failure Patients

NCT01439009 | Completed Phase 4 Results

• 2 other identifiers: 156-10-005JapicCTI-111621
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 8

Brief 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 prognosis of the target population. The efficacy of tolvaptan during the treatment period will also be investigated.

Conditions

Heart Failure

Keywords

Heart failure; Volume overload; Tolvaptan; loop diuretics

Outcome Measures

Primary Outcomes (13)

• 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 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)

  Week 26

• Mortality （Number of Death）

  Statistical comparison was not done.

  Week26

• Body Weight

  The comparison of the average of amount of change from baseline. Statistical comparison was not done.

  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.

  Day15

• Jugular Venous Distension

  The comparison of the average of amount of change from baseline. Statistical comparison was not done.

  Day15

• Change in Liver Size From Baseline

  The comparison of the average of amount of change from baseline. Statistical comparison was not done．

  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.

  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.

  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.

  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.

  Day15

• Plasma Brain Natriuretic Peptide (BNP) Concentration

  The comparison of the average of amount of change from baseline. Statistical comparison was not done.

  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.

  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.

  The day after last IMP administration and Baseline

Study Arms (2)

Tolvaptan

EXPERIMENTAL

15 mg

Drug: Tolvaptan

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo of tolvaptan

Interventions

Tolvaptan DRUG

Once-daily oral administration of one tolvaptan 15 mg tablet in the morning

Tolvaptan

Placebo of tolvaptan DRUG

Once-daily oral administration of one placebo tablet in the morning

Placebo

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Hyponatremia (serum sodium concentration \< 125 mEq/L)
• 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

Sponsors & Collaborators

• Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (8)

Unknown Facility

Chube Region, Japan

Location

Unknown Facility

Chushikoku Region, Japan

Location

Unknown Facility

Hokkaido Region, Japan

Location

Unknown Facility

Hokuriku Region, Japan

Location

Unknown Facility

Kansai Region, Japan

Location

Unknown Facility

Kanto Region, Japan

Location

Unknown Facility

Kyushu Region, Japan

Location

Unknown Facility

Tohoku Region, Japan

Location

MeSH Terms

Conditions

Heart Failure; Edema

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director of Clinical Research and Development
• Organization: Otsuka Pharmaceutical Co., Ltd

+81-3-6361-7366

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2011
• First Posted: September 22, 2011
• Study Start: September 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: October 22, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-10

Locations

JP (8)