A Multicenter, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tolvaptan in the Treatment of Cardiac-Induced Edema in Patients With Heart Failure

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Taiwan Otsuka Pharm. Co., Ltd
Sponsor:
Information provided by (Responsible Party):
Taiwan Otsuka Pharm. Co., Ltd
ClinicalTrials.gov Identifier:
NCT01618448
First received: June 5, 2012
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

A Multicenter, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tolvaptan in the Treatment of Cardiac-Induced Edema in Patients with Heart Failure


Condition Intervention Phase
Cardiac-induced Edema
Drug: Tolvaptan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Tolvaptan in the Treatment of Cardiac-Induced Edema in Patients With Heart Failure

Resource links provided by NLM:


Further study details as provided by Taiwan Otsuka Pharm. Co., Ltd:

Primary Outcome Measures:
  • Change in body weight at 4-day of treatment. [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Intake/Output Balance at 4-day of Treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • Change in Serum Sodium and Potassium Concentration at 4-day of treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • Treatment Failure at 4-day of Treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • Changes in Physician-assessed Signs and Symptoms of Heart Failure at 4-day of Treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • Changes in Patient Self-assessed Global Clinical Status at 4-day of Treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • Changes in Patient Self-assessed Dyspnea Status at 4-day of Treatment [ Time Frame: baseline and 4-day of treatment ] [ Designated as safety issue: No ]
  • All-cause Mortality during the Study Period [ Time Frame: Duration of hospital stay for 4 days, post-study follow up visit for 2 times ] [ Designated as safety issue: Yes ]
    Total timeframe expected average of 37 days for each participant


Estimated Enrollment: 88
Study Start Date: July 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Placebo
Placebo once daily
Drug: Placebo
Placebo
Experimental: Tolvaptan
Tolvaptan 15mg once daily
Drug: Tolvaptan
Tolvaptan 15mg once daily

  Eligibility

Ages Eligible for Study:   20 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients aged 20 to 85 years old, inclusive, at the Screening Period
  2. Patients with history of chronic HF hospitalized primarily for worsening HF with signs or symptoms of volume congestion in spite of standard therapy
  3. Patient should have HF symptoms at rest or minimal exertion and signs of congestion (lower limb edema, jugular venous distention, or pulmonary congestion due to extracellular volume expansion) at time of randomization c. Anti-aldosterone drugs: Spironolactone, Triamterene
  4. Patients undergoing any of the following diuretic therapies:

    • A loop diuretic at a daily dosage equivalent to 40 mg or more of furosemide
    • Concomitant administration of a loop diuretic and a thiazide diuretic (at any doses)
    • Concomitant administration of a loop diuretic and an anti-aldosterone drug (at any doses)

    Note: The allowable types and dosages of the concomitantly administered diuretics are specified as follows:

    1. Loop diuretics equivalent to 40 mg of furosemide:

      Bumetanide: 1 mg, Piretanide: 6 mg, Azosemide: 60 mg, Torasemide: 8 mg

    2. Thiazide diuretics: Hydrochlorothiazide, Trichloromethiazide, Benzyl hydrochlorothiazide, Chlortalidone, Mefruside
  5. Patients who had been taking an orally administered diuretic without any change in dose or mode of administration during Observation period
  6. Patients whose body weight variation was within 1.0 kg during the 2 days prior start of treatment
  7. Patients able to accomplish with study procedures from Screening period to Post-study follow-up
  8. Patients capable of giving informed consent to participate in the study of their own free will.

Exclusion Criteria:

  1. Cardiac surgery within 60 days of enrollment
  2. Patients with an assisted cardiac mechanical device
  3. Patients receiving CRT (Cardiac Resynchronization Therapy) within 60 days of enrollment.
  4. Patients with active or significant complications or symptoms as follow:

    • Suspected decrease in circulatory blood flow
    • Refractory end-stage HF (patients considered to require mechanical circulatory support, continuous intravenous positive inotropic therapy, referral of cardiac transplantation, or hospice care)
    • Cardiac valvular disease with significant heart valve stenosis
    • Sustained ventricular tachycardia or ventricular fibrillation within 30 days prior to screening examination
    • Acute myocardial infarction within 30 days prior to screening examination
    • Cerebrovascular disorders within 6 months prior to screening examination (other than asymptomatic cerebral infarction)
    • Patients with a definite diagnosis of active myocarditis or amyloid cardiomyopathy
    • Poorly controlled Diabetes Mellitus (HbAlc 10%)
    • Anuria (urinary output less than 100 ml per day)
    • History of Hyperthyroidism
    • Urination impaired due to urinary tract stricture, urinary calculus, tumor in urinary tract, or other cause
    • Hemofiltration or dialysis
    • Patients unable to sense thirst, inappropriately respond to thirst or those who have impaired oral fluid intake.
  5. Patients with a history of hypersensitivity or idiosyncratic reaction to benzazepine derivatives such as mozavaptan hydrochloride or benazepril hydrochloride
  6. Patients who are severely obese (BMI exceeding 35 kg/m2)
  7. Patients with systolic blood pressure in the decubitus position below 90 mmHg
  8. Patients with any of following abnormal laboratory values:

    Total bilirubin exceeding 3.0 mg/dL, hemoglobin of less than 9 g/dL, serum creatinine exceeding 3.0 mg/dL, serum sodium exceeding 147 mEq/L, or serum potassium exceeding 5.5 mEq/L

  9. Female patients who are pregnant, possibly pregnant, or lactating, or who plan to become pregnant
  10. Patients who received any investigational drug other than Tolvaptan within 30 days prior to the screening examination
  11. Patients with general physical conditions, which may confound the results of the study, pose additional risk or preclude evaluation and assessments in this study
  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: NCT01618448

Contacts
Contact: Edward Peng (+)886-2-2505-2868 ext 317 edward_peng@otsuka.co.tw

Locations
Taiwan
National Taiwan University Hospita Recruiting
Taipei, Taiwan
Contact: Edward Peng       edward_peng@otsuka.co.tw   
Principal Investigator: Chuen Den Tseng, MD PhD         
Sponsors and Collaborators
Taiwan Otsuka Pharm. Co., Ltd
  More Information

No publications provided

Responsible Party: Taiwan Otsuka Pharm. Co., Ltd
ClinicalTrials.gov Identifier: NCT01618448     History of Changes
Other Study ID Numbers: 156-TWA-1101
Study First Received: June 5, 2012
Last Updated: January 15, 2013
Health Authority: Taiwan : Food and Drug Administration

Additional relevant MeSH terms:
Edema
Heart Failure
Edema, Cardiac
Signs and Symptoms
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014