- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02352285
Outcome and Treatment Quality Study of Tolvaptan to Treat Hyponatremia in Patients With Heart Failure (AQUATIC)
June 12, 2017 updated by: Korea Otsuka Pharmaceutical Co., Ltd.
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
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
58
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Seoul, Korea, Republic of
- Seoul National University Bundang Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
20 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tolvaptan
Tovaptan tablet 15mg, 30mg, 60mg, once a day, oral
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Start with 15mg to titrate upwards to 30mg to 60mg, once a daily
Other Names:
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Placebo Comparator: placebo
placebo tablet 15mg, 30mg, 60mg, once a day, oral
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Start with 15mg to titrate upwards to 30mg to 60mg, once a daily
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
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from baseline to day 4
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Average amount of furosemide used during hospitalization.
Time Frame: from day 1 to discharge date (up to subject condition day 2 ~ day 30)
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from day 1 to discharge date (up to subject condition day 2 ~ day 30)
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Average amount of furosemide used during out-patient period.
Time Frame: from baseline to day 30 and day 60
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from baseline to day 30 and day 60
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Dongju Choi, MD, Seoul National University Bundang Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2012
Primary Completion (Actual)
January 1, 2017
Study Completion (Actual)
January 1, 2017
Study Registration Dates
First Submitted
December 20, 2012
First Submitted That Met QC Criteria
January 27, 2015
First Posted (Estimate)
February 2, 2015
Study Record Updates
Last Update Posted (Actual)
June 14, 2017
Last Update Submitted That Met QC Criteria
June 12, 2017
Last Verified
November 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 156-KOB-1201i
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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