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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Korea Otsuka Pharmaceutical Co.,Ltd.
Sponsor:
Information provided by (Responsible Party):
Korea Otsuka Pharmaceutical Co.,Ltd.
ClinicalTrials.gov Identifier:
NCT02352285
First received: December 20, 2012
Last updated: February 11, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Heart Failure With Hyponatremia
Drug: Tolvaptan
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Korea Otsuka Pharmaceutical Co.,Ltd.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Average amount of furosemide used during hospitalization. [ Time Frame: from day 1 to discharge date (up to subject condition day 2 ~ day 30) ] [ Designated as safety issue: Yes ]
  • Average amount of furosemide used during out-patient period. [ Time Frame: from baseline to day 30 and day 60 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tolvaptan
Tovaptan tablet 15mg, 30mg, 60mg, once a day, oral
Drug: Tolvaptan
Start with 15mg to titrate upwards to 30mg to 60mg, once a daily
Other Name: Samsca
Placebo Comparator: placebo
placebo tablet 15mg, 30mg, 60mg, once a day, oral
Drug: Placebo
Start with 15mg to titrate upwards to 30mg to 60mg, once a daily

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.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02352285

Contacts
Contact: Ho Young Lee, BS +82-2-3287-9238 hoyounglee@otsuka.co.kr

Locations
Korea, Republic of
Seoul National University Bundang Hospital Recruiting
Seoul, Korea, Republic of
Contact: Dong Ju Choi, Doctor    82-31-787-7007    djchoi@snubh.org   
Sponsors and Collaborators
Korea Otsuka Pharmaceutical Co.,Ltd.
Investigators
Principal Investigator: Dongju Choi, MD Seoul National University Bundang Hospital
  More Information

No publications provided

Responsible Party: Korea Otsuka Pharmaceutical Co.,Ltd.
ClinicalTrials.gov Identifier: NCT02352285     History of Changes
Obsolete Identifiers: NCT01865214
Other Study ID Numbers: 156-KOB-1201i
Study First Received: December 20, 2012
Last Updated: February 11, 2015
Health Authority: Korea: Ministry of Food and Drug Safety

Additional relevant MeSH terms:
Heart Failure
Hyponatremia
Cardiovascular Diseases
Heart Diseases
Metabolic Diseases
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on May 21, 2015