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 May 2013 by Korea Otsuka International Asia Arab
Sponsor:
Collaborator:
Korea Otsuka Pharmaceutical Co.,Ltd.
Information provided by (Responsible Party):
Korea Otsuka International Asia Arab
ClinicalTrials.gov Identifier:
NCT01865214
First received: May 27, 2013
Last updated: NA
Last verified: May 2013
History: No changes posted
  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
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
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 International Asia Arab:

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: No ]

Estimated Enrollment: 100
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tolvaptan Drug: Tolvaptan
to titrate upwards to 15mg to 60mg, once a daily
Placebo Comparator: Placebo

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 [Appendix 4]) prior to randomization.

    2. Male and female patients aged ≥ 20 years. 3. Subject who diagnosed with heart failure and 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 (such as barrier contraceptives or methods that result in a failure rate of less than 1%).

    2. Patients with hyponatremia in hypovolemic states, defined as the presence of clinical and historical evidence of extracellular fluid volume depletion, including but not limited to skin turgor, orthostatic changes in blood pressure (BP) or heart rate (HR), dry mucous membranes, or a response to i.v. saline challenge.

    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), e.g. new femoral fracture surgery requiring extended recovery.

    5. Patients with recent prior treatment for hyponatremia, such as hypertonic saline (within 8 h, just before the administration) or urea, lithium or tolvaptan (within 4 days, just before the administration) .

    6. Patients with severe hyponatremia symptoms requiring immediate intervention with hypertonic saline; or who are expected to require such therapy within 48 h after randomization.

    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 (e.g. hyper- or hypo- oxemia, glycaemia, calcemia, ammonemia, etc.) 8. Patients with acute and transient hyponatremia associated with head trauma or severe neurological injury (e.g. stroke, subdural hematoma).

    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. Note, if it is confirmed under the BP<90mmHg at the first attempt, in addition, conduct a test twice more. And if it fits two results out of three in the criteria, the subject can be enrolled.

    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 defined as glucose > 300 mg/dL (16.7 mmol/L) without regard to meals.

    15. Patients with a current urinary tract obstruction (e.g. obstructive benign prostatic hypertrophy).

    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 (e.g. 30 day) survival.

    19. Patients whose hyponatremia is the result of any medication that cannot safely be withdrawn, such as anti-convulsants (e.g. carbamazepine) and anti psychotics (e.g. haloperidol).

    20. Patients receiving desmopressin within 2 days of screening. 21. Patients who have participated in another investigational drug trial within the past 30 days(except for Non-interventional study).

    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. (ex, severe pneumonia, infectious disease and etc.) 23. Patients treated and/or to be treated with strong cytochrome P450 (CYP) 3A inhibitors (clarithromycin, ketoconazole, itraconazole, ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin).

    24. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose- galactose malabsorption.

    25.Patients with Aspartate transaminase(AST) or alanine transaminase(ALT) >2.5 times the upper limit of normal(UNL), total bilirubin > 2mg/dL or who under any medication treatment for liver disease at screening"

  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: NCT01865214

Contacts
Contact: Dong Ju Choi, Doctor 82-31-787-7007 djchoi@snubh.org

Locations
Korea, Republic of
Seoul National University Bundang Hospital Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
Contact: Dong Ju Choi, Doctor    82-31-787-7007    djchoi@snubh.org   
Sponsors and Collaborators
Korea Otsuka International Asia Arab
Korea Otsuka Pharmaceutical Co.,Ltd.
  More Information

No publications provided

Responsible Party: Korea Otsuka International Asia Arab
ClinicalTrials.gov Identifier: NCT01865214     History of Changes
Other Study ID Numbers: 156-KOB-1201i
Study First Received: May 27, 2013
Last Updated: May 27, 2013
Health Authority: Korea: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 20, 2014