Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management (Secret of CHF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Cardiovascular Clinical Science Foundation
Sponsor:
Information provided by (Responsible Party):
Cardiovascular Clinical Science Foundation
ClinicalTrials.gov Identifier:
NCT01584557
First received: April 10, 2012
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to evaluate the short term efficacy and safety of tolvaptan in subjects hospitalized for worsening heart failure who have volume overload and one of the following: renal insufficiency, or hyponatremia or inadequate response to diuretic therapy. The primary variable for assessing efficacy will be self-assessed 7-point dyspnea score at 8 and 16 hours.


Condition Intervention Phase
Heart Failure
Drug: Tolvaptan or Samsca
Drug: placebo or sugar pill
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management

Resource links provided by NLM:


Further study details as provided by Cardiovascular Clinical Science Foundation:

Primary Outcome Measures:
  • To evaluate the short term efficacy and safety of tolvaptan in subjects hospitalized for worsening heart failure who have volume overload and one of the following: renal insufficiency, or hyponatremia or inadequate response to diuretic therapy. [ Time Frame: 8 and 16 hours ] [ Designated as safety issue: No ]
    The primary variable for assessing efficacy will be self-assessed 7-point dyspnea score at 8 and 16 hours.


Secondary Outcome Measures:
  • Change from baseline in body weight measured daily while hospitalized up to 7 days. [ Time Frame: up to 7 days ] [ Designated as safety issue: Yes ]
    Change from baseline in body weight measured daily while hospitalized up to 7 days.

  • Diuretic dose measured daily while hospitalized up to 7 days. [ Time Frame: up to 7 days. ] [ Designated as safety issue: Yes ]
    Diuretic dose measured daily while hospitalized up to 7 days.

  • Change from baseline in estimated glomerular filtration rate (eGFR) at discharge or day 7, whichever comes first. [ Time Frame: at discharge or day 7, whichever comes first. ] [ Designated as safety issue: Yes ]
    Change from baseline in estimated glomerular filtration rate (eGFR) at discharge or day 7, whichever comes first.

  • Days alive and out of the hospital over 30 days [ Time Frame: 30 days. ] [ Designated as safety issue: No ]
    Days alive and out of the hospital over 30 days

  • Change from baseline in cognitive function at 48 hours or discharge, whichever comes first [ Time Frame: at 48 hours or dischage, whichever comes first ] [ Designated as safety issue: No ]
    Change from baseline in cognitive function at 48 hours or discharge, whichever comes first

  • Re-hospitalization for worsening heart failure or death at 30 days [ Time Frame: 30 days. ] [ Designated as safety issue: Yes ]
    Re-hospitalization for worsening heart failure or death at 30 days


Estimated Enrollment: 250
Study Start Date: June 2012
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tolvaptan, Samsca
Tolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days.
Drug: Tolvaptan or Samsca
uncoated tablet, 30mg, once per day, for up to 7 days.
Other Name: tolvaptan or Samsca
Placebo Comparator: sugar pill
placebo, sugar pill
Drug: placebo or sugar pill
sugar pill
Other Name: placebo or sugar pill

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects hospitalized for worsening heart failure and randomized within 36 hours of initial presentation.
  2. Males and females 18 years of age or older.
  3. NYHA Class III or IV on admission to the hospital.
  4. Able to understand content of and willing to provide written informed consent
  5. Dyspnea, measured by the 5-point current dyspnea scale (moderately short of breath or worse), within 2 hours of randomization and dosing.

    The following must be met within 12 hours of randomization.

  6. The subject must have signs of extracellular volume expansion, defined as two or more of the following five: Signs of RHF ( jugular venous distention, pitting edema (≥1+), ascites) and/or Signs of LHF (pulmonary congestion on chest x-ray, pulmonary rales)
  7. Have at least one of the following:

    • eGFR < 60ml/min/1.73m2, OR
    • serum sodium ≤ 134 mEq/L, OR
    • urine output ≤ 125 ml/hr over anytime frame of at least 2 hours, following administration of IV furosemide of at least 40mg. See table below.

Time Period (hr) Cumulative UO (mL) 2 <250 3 <375 4 <500 5 <625 6 <750 7 <875 8 <1000

Exclusion Criteria:

  1. Positive urine pregnancy test for women of child bearing potential.
  2. Inability to provide written informed consent.
  3. Cardiac surgery within 60 days prior to study randomization.
  4. Acute Coronary Syndrome (ACS) or percutaneous coronary intervention within 30 days prior to study randomization.
  5. Planned revascularization procedures, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study randomization.
  6. Planned electrophysiologic (EP) device implantation within 7 days following study randomization.
  7. Subjects who are on cardiac mechanical support.
  8. Co-morbid condition with an expected survival less than six months.
  9. History of a cerebrovascular accident within the last 30 days.
  10. Hemodynamically significant uncorrected primary cardiac valvular disease.
  11. Hypertrophic cardiomyopathy (obstructive or non-obstructive).
  12. Uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
  13. History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
  14. Chronic uncontrolled diabetes mellitus as determined by the investigator.
  15. Supine systolic arterial blood pressure < 90 mmHg.
  16. Serum creatinine > 3.5 mg/dL or undergoing dialysis.
  17. Hemoglobin < 9 g/dL
  18. History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazepril).
  19. Inability to take oral medications.
  20. Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted.
  21. Previous exposure to tolvaptan within 7 days prior to randomization.
  22. Subjects with refractory, end-stage, heart failure defined as subjects who are appropriate candidates for specialized treatment strategies, such as ventricular assist devices, continuous positive IV inotropic therapy, or hospice care.
  23. Ultrafiltration within 7 days prior to randomization or planned.
  24. Active gout
  25. Serum sodium >144 mEq/L
  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: NCT01584557

Contacts
Contact: Matthew E Romeling, MHA 617-423-7999 ext 109 mromeling@ccstrials.com
Contact: Patricia Wedge, RN 617-423-7999 ext 118 pwedge@ccstrials.com

  Show 44 Study Locations
Sponsors and Collaborators
Cardiovascular Clinical Science Foundation
Investigators
Principal Investigator: Marvin Konstam, MD Cardiovascular Clinical Science Foundation
  More Information

No publications provided

Responsible Party: Cardiovascular Clinical Science Foundation
ClinicalTrials.gov Identifier: NCT01584557     History of Changes
Other Study ID Numbers: CCSF-2011-001
Study First Received: April 10, 2012
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases
Contraceptives, Oral
Contraceptive Agents
Contraceptive Agents, Female
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014