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

NCT ID: NCT02352285

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2017-01-31

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.

Conditions

Heart Failure With Hyponatremia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Tolvaptan

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

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Start with 15mg to titrate upwards to 30mg to 60mg, once a daily

placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Start with 15mg to titrate upwards to 30mg to 60mg, once a daily

Interventions

Tolvaptan

Start with 15mg to titrate upwards to 30mg to 60mg, once a daily

Intervention Type: DRUG

Placebo

Start with 15mg to titrate upwards to 30mg to 60mg, once a daily

Intervention Type: DRUG

Other Intervention Names

Samsca

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Korea Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dongju Choi, MD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Bundang Hospital

Locations

Seoul National University Bundang Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

156-KOB-1201i

Identifier Type: -

Identifier Source: org_study_id

NCT01865214

Identifier Type: -

Identifier Source: nct_alias