Efficacy and Safety of Tolvaptan in Japanese Patients With Acute Heart Failure (MT FUJI)

Multicenter Tolvaptan Study For Uncontrolled Volume Overload in Japanese Acute Decompensated Heart faIlure Patients: A Prospective Observational Multicenter Cohort Study

The aims of the present study are to investigate prospectively the clinical course and outcome of the hospitalized heart failure patients treated with tolvaptan for management of fluid retention and serum sodium levels of less than 140 mEq/L and also to analyze the factors related with the efficacy including outcome of tolvaptan therapy.

Study Overview

• Status: Completed
• Conditions: Heart Failure

Detailed Description

Vasopressin mediates fluid retention in heart failure. Tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, shows promise for management of heart failure.

• Study Type: Observational
• Enrollment (Actual): 274

Contacts and Locations

Study Locations

• Japan
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 211-8533
      • Nippon Medical School, Musashi Kosugi Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients hospitalized for decompensated heart failure with fluid retention and serum sodium levels of less than 140 mEq/L

Description

Inclusion Criteria:

1. hospitalized patients for decompensated heart failure with signs of fluid retention despite using diuretics other than tolvaptan and planned tolvaptan use
2. serum Na < 140 mEq/L
3. age: > or = 20 years at the time of informed consent
4. provided written informed consent.

Exclusion Criteria:

1. hemodynamic instability
2. patients with hypersensitivity to tolvaptan or similar compounds
3. anuric patients
4. patients who cannot feel thirst and are difficult to intake the fluid
5. patients who are pregnant, potentially pregnant or willing to be pregnant
6. patients have taken tolvaptan before enrollment after hospitalization
7. acute coronary syndrome
8. adrenal insufficiency
9. patients scheduled to undergo coronary angioplasty within the study period
10. ineligible patients according to the investigator's judgment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Tolvaptan; Tolvaptan administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy 1) Alleviation of the signs of body fluid retention 2) Change of body weight 3) Changes in the daily urinary volume	1) Alleviation of the signs of body fluid retention by the 7th day of treatment with tolvaptan (or the day of discontinuation of the drug in cases where tolvaptan treatment has been discontinued before the 7th day) as compared with the observations made on the day before the start of treatment 2) Change of body weight by the 7th day of treatment with tolvaptan as compared with the level measured on the day before the start of treatment 3) Changes in the daily urinary volume by the 7th day of treatment with tolvaptan as compared with the values measured on the day before the start of treatment	At the day of discontinuation of tolvaptan or day 7, whichever comes first
Safety: adverse events Adverse events until 30 days after the end of treatment with tolvaptan		30 days after tolvaptan withdrawal
Long-term outcome (1 year after tolvaptan administration) 1) Time from enrollment to cardiovascular events 2) Time from enrollment to re-hospitalization for aggravation of heart failure 3) Time from enrollment to all-cause death	1) Time from enrollment to cardiovascular events within 1 year after administration of tolvaptan 2) Time from enrollment to re-hospitalization for aggravation of heart failure within 1 year after administration of tolvaptan 3) Time from enrollment to all-cause death within 1 year after administration of tolvaptan Cardiovascular events included death from heart failure, death from acute coronary syndrome, death from stroke, sudden death, death of unknown causes, death from other cardiovascular causes, readmission for heart failure, ventricular arrhythmia, acute coronary syndrome, and stroke.	1 year after administration of tolvaptan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Search for the factors related with the efficacy of tolvaptan therapy and long-term outcome 1) related factors regarding efficacy of tolvaptan 2 ) related factors regarding long-term outcome	Exploratory analysis will be performed to determine which factors relate with the efficacy of tolvaptan therapy or long-term outcome. Factors will include age, gender, medical past history, medication, NYHA classification, Nohria/Steavenson classification, laboratory data (Na, K, Cl, Albumin, Cr, BUN, AST, ALT, gamma-GTP, LDH, T-Bil, BNP, NT-pro BNP, copeptin, galectin-3,aldosteron,angiotensin II, renin, noradrenaline), heart rate, blood pressure, echocardiography data, intake/urine volume and osmolality.	1 year after administration of tolvaptan

Collaborators and Investigators

• Sponsor: Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
• Collaborators: Nippon Medical School, Musashi Kosugi Hospital
• Investigators: Principal Investigator: Naoki Sato, MD,PhD, Nippon Medical School, Musashi Kosugi Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2012
• Primary Completion (Actual): December 31, 2015
• Study Completion (Actual): December 31, 2015

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 6, 2012
• First Posted (Estimate): July 9, 2012

Study Record Updates

• Last Update Posted (Actual): June 2, 2017
• Last Update Submitted That Met QC Criteria: June 1, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Diuretics; Sodium; Vasopressins
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: TRIHF1203; UMIN000008258 (Registry Identifier: UMIN Clinical Trials Registry)