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

Otsuka

Status and phase

Terminated

Phase 4

Conditions

Heart Failure With Hyponatremia

Treatments

Drug: Placebo

Drug: Tolvaptan

Study type

Interventional

Funder types

Industry

Identifiers

NCT02352285

156-KOB-1201i

Details and patient eligibility

About

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.

Full 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.

Enrollment

58 patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

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