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Outcome and Treatment Quality Study of Tolvaptan to Treat Hyponatremia in Patients With Heart Failure (AQUATIC)

Primary Purpose

Heart Failure With Hyponatremia

Status
Terminated
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Tolvaptan
Placebo
Sponsored by
Korea Otsuka Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Hyponatremia

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients hospitalized due to heart failure with clinically significant hyponatremia (except hypovolemic) (defined as serum Na < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) prior to randomization.
  2. Male and female patients aged ≥ 20 years.
  3. New York Heart Association (NYHA) class III/Ⅳ
  4. Signs of extracellular volume expansion, defined as two or more of the following: JVD, peripheral edema, dyspnea or pulmonary congestion.
  5. B-type natriuretic peptide (BNP) ≥ 150 pg/mL or N terminal (NT)-proBNP ≥ 450 pg/mL.

Exclusion Criteria:

  1. Women who are pregnant, breast feeding, or of childbearing potential who are not using acceptable contraceptive methods
  2. Patients with hyponatremia in hypovolemic states, defined as the presence of clinical and historical evidence of extracellular fluid volume depletion
  3. Patients unable to sense or respond to thirst.
  4. Patients who are likely to require prolonged hospitalization for reasons other than chronic heart failure (CHF)
  5. Patients with recent prior treatment for hyponatremia
  6. Patients with severe hyponatremia symptoms requiring immediate intervention with hypertonic saline
  7. Patients with causes of neurological symptoms, which are attributable to psychological (psychoses), structural (dementia of the Alzheimer's type, post-infarct dementia) or other metabolic causes
  8. Patients with acute and transient hyponatremia associated with head trauma or severe neurological injury
  9. Patients with a history of hyponatremia known to be due to severe, untreated hypothyroidism/adrenal insufficiency.
  10. Patients with psychogenic polydipsia.
  11. Patients with systolic BP < 90 mmHg at screening.
  12. Patients with a history of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril), or tolvaptan.
  13. Patients with a history of drug or medication abuse within the 3 months prior to screening, or current alcohol abuse.
  14. Patients with uncontrolled diabetes mellitus
  15. Patients with a current urinary tract obstruction
  16. Anuric patients.
  17. Patients with a serum creatinine > 3.5 mg/dL at screening.
  18. Terminally ill patients or patients with a moribund condition who have little chance of short-term survival.
  19. Patients whose hyponatremia is the result of any medication that cannot safely be withdrawn, such as anti-convulsants and anti psychotics
  20. Patients receiving desmopressin within 2 days of screening.
  21. Patients who have participated in another investigational drug trial within the past 30 days.
  22. Any patient who, in the opinion of the investigator, would not be able to comply with the study drug administration or study procedures, or whose overall medical condition would prohibit their participation in the study.
  23. Patients treated and/or to be treated with strong cytochrome P450 (CYP) 3A inhibitors
  24. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose- galactose malabsorption.
  25. Patients with a AST or ALT > ULN 2.5 or total bilirubin > 2mg/dL

Sites / Locations

  • Seoul National University Bundang Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tolvaptan

placebo

Arm Description

Tovaptan tablet 15mg, 30mg, 60mg, once a day, oral

placebo tablet 15mg, 30mg, 60mg, once a day, oral

Outcomes

Primary Outcome Measures

Average daily AUC of change from baseline in serum Na level to day 4 within the double-blind treatment period

Secondary Outcome Measures

Average amount of furosemide used during hospitalization.
Average amount of furosemide used during out-patient period.

Full Information

First Posted
December 20, 2012
Last Updated
June 12, 2017
Sponsor
Korea Otsuka Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02352285
Brief Title
Outcome and Treatment Quality Study of Tolvaptan to Treat Hyponatremia in Patients With Heart Failure
Acronym
AQUATIC
Official Title
Assessment of Clinical Outcome and Treatment Quality Under Adequate Use of Tolvaptan In Correction of Hyponatremia in Patients Hospitalized With Worsening Heart Failure and Hyponatremia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Terminated
Study Start Date
December 2012 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Korea Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective is to evaluate the efficacy and safety on the tolvaptan for increasing serum Na levels in patients with worsening heart failure and hyponatremia.
Detailed Description
This is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group interventional study comparing tolvaptan (15 to 60 mg) to placebo in adult patients hospitalized (or admission to emergency room) due to worsening of heart failure and dilutional hyponatremia. All patients will be on standard therapy for heart failure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Hyponatremia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tolvaptan
Arm Type
Experimental
Arm Description
Tovaptan tablet 15mg, 30mg, 60mg, once a day, oral
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo tablet 15mg, 30mg, 60mg, once a day, oral
Intervention Type
Drug
Intervention Name(s)
Tolvaptan
Other Intervention Name(s)
Samsca
Intervention Description
Start with 15mg to titrate upwards to 30mg to 60mg, once a daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Start with 15mg to titrate upwards to 30mg to 60mg, once a daily
Primary Outcome Measure Information:
Title
Average daily AUC of change from baseline in serum Na level to day 4 within the double-blind treatment period
Time Frame
from baseline to day 4
Secondary Outcome Measure Information:
Title
Average amount of furosemide used during hospitalization.
Time Frame
from day 1 to discharge date (up to subject condition day 2 ~ day 30)
Title
Average amount of furosemide used during out-patient period.
Time Frame
from baseline to day 30 and day 60

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients hospitalized due to heart failure with clinically significant hyponatremia (except hypovolemic) (defined as serum Na < 125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction) prior to randomization. Male and female patients aged ≥ 20 years. New York Heart Association (NYHA) class III/Ⅳ Signs of extracellular volume expansion, defined as two or more of the following: JVD, peripheral edema, dyspnea or pulmonary congestion. B-type natriuretic peptide (BNP) ≥ 150 pg/mL or N terminal (NT)-proBNP ≥ 450 pg/mL. Exclusion Criteria: Women who are pregnant, breast feeding, or of childbearing potential who are not using acceptable contraceptive methods Patients with hyponatremia in hypovolemic states, defined as the presence of clinical and historical evidence of extracellular fluid volume depletion Patients unable to sense or respond to thirst. Patients who are likely to require prolonged hospitalization for reasons other than chronic heart failure (CHF) Patients with recent prior treatment for hyponatremia Patients with severe hyponatremia symptoms requiring immediate intervention with hypertonic saline Patients with causes of neurological symptoms, which are attributable to psychological (psychoses), structural (dementia of the Alzheimer's type, post-infarct dementia) or other metabolic causes Patients with acute and transient hyponatremia associated with head trauma or severe neurological injury Patients with a history of hyponatremia known to be due to severe, untreated hypothyroidism/adrenal insufficiency. Patients with psychogenic polydipsia. Patients with systolic BP < 90 mmHg at screening. Patients with a history of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril), or tolvaptan. Patients with a history of drug or medication abuse within the 3 months prior to screening, or current alcohol abuse. Patients with uncontrolled diabetes mellitus Patients with a current urinary tract obstruction Anuric patients. Patients with a serum creatinine > 3.5 mg/dL at screening. Terminally ill patients or patients with a moribund condition who have little chance of short-term survival. Patients whose hyponatremia is the result of any medication that cannot safely be withdrawn, such as anti-convulsants and anti psychotics Patients receiving desmopressin within 2 days of screening. Patients who have participated in another investigational drug trial within the past 30 days. Any patient who, in the opinion of the investigator, would not be able to comply with the study drug administration or study procedures, or whose overall medical condition would prohibit their participation in the study. Patients treated and/or to be treated with strong cytochrome P450 (CYP) 3A inhibitors Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose- galactose malabsorption. Patients with a AST or ALT > ULN 2.5 or total bilirubin > 2mg/dL
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dongju Choi, MD
Organizational Affiliation
Seoul National University Bundang Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Bundang Hospital
City
Seoul
Country
Korea, Republic of

12. IPD Sharing Statement

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Outcome and Treatment Quality Study of Tolvaptan to Treat Hyponatremia in Patients With Heart Failure

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