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Secret of CHF: 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

Sponsor
Cardiovascular Clinical Science Foundation (Other)
Overall Status
Completed
CT.gov ID
NCT01584557
Collaborator
(none)
250
Enrollment
37
Locations
2
Arms
50
Duration (Months)
6.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Drug: Tolvaptan or Samsca
  • Drug: placebo or sugar pill
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
250 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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
Study Start Date :
Jun 1, 2012
Actual Primary Completion Date :
Jul 1, 2016
Actual Study Completion Date :
Aug 1, 2016

Arms and Interventions

Arm Intervention/Treatment
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.
Placebo Comparator: sugar pill

placebo, sugar pill

Drug: placebo or sugar pill
sugar pill

Outcome Measures

Primary Outcome Measures

  1. 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. [8 and 16 hours]

    The primary variable for assessing efficacy will be self-assessed 7-point dyspnea score at 8 and 16 hours.

Secondary Outcome Measures

  1. Change from baseline in body weight measured daily while hospitalized up to 7 days. [up to 7 days]

    Change from baseline in body weight measured daily while hospitalized up to 7 days.

  2. Diuretic dose measured daily while hospitalized up to 7 days. [up to 7 days.]

    Diuretic dose measured daily while hospitalized up to 7 days.

  3. Change from baseline in estimated glomerular filtration rate (eGFR) at discharge or day 7, whichever comes first. [at discharge or day 7, whichever comes first.]

    Change from baseline in estimated glomerular filtration rate (eGFR) at discharge or day 7, whichever comes first.

  4. Days alive and out of the hospital over 30 days [30 days.]

    Days alive and out of the hospital over 30 days

  5. Change from baseline in cognitive function at 48 hours or discharge, whichever comes first [at 48 hours or dischage, whichever comes first]

    Change from baseline in cognitive function at 48 hours or discharge, whichever comes first

  6. Re-hospitalization for worsening heart failure or death at 30 days [30 days.]

    Re-hospitalization for worsening heart failure or death at 30 days

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  1. 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)

  2. 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

Locations

Site City State Country Postal Code
1 University of Alabama at Birmingham Birmingham Alabama United States 35294
2 The Heart Center Research Huntsville Alabama United States 35801
3 Greater Los Angeles VA Medical Center Los Angeles California United States 90073
4 University of Florida Health Science Ctr. Jacksonville Jacksonville Florida United States 32209
5 MIMA Century Research Associates Melbourne Florida United States 32901
6 Jackson Memorial Hospital Miami Florida United States 33136
7 Emory University Atlanta Georgia United States 30322
8 University Cardiology Associates, LLC Augusta Georgia United States 30901
9 Mercer University School of Medicine Macon Georgia United States 31201
10 Advocate Medical Group - Oakbrook Naperville Illinois United States 60540
11 Advocate Christ Medical Center Oak Lawn Illinois United States 60453
12 St. Vincent Medical Group Indianapolis Indiana United States 46260
13 CardioSpecialists Group Munster Indiana United States 46321
14 Ochsner Medical Center New Orleans Louisiana United States 70121
15 Advanced Cardiovascular Specialists Shreveport Louisiana United States 71135
16 Louisiana Heart Center and Research Slidell Louisiana United States 70458
17 University of Maryland Baltimore Maryland United States 21201
18 Tufts Medical Center Boston Massachusetts United States 02111
19 Lahey Hospital and Medical Center Burlington Massachusetts United States 01805
20 Crittenton Hospital Medical Center Rochester Michigan United States 48307
21 Minneapolis Heart Institute Minneapolis Minnesota United States 55407
22 Bryan Heart Institute Lincoln Nebraska United States 68506
23 The Valley Hospital Ridgewood New Jersey United States 07450
24 Caromont Heart/Gaston Memorial Hospital Gastonia North Carolina United States 28054
25 Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente Lumberton North Carolina United States 28358
26 Akron General Medical Center Akron Ohio United States 44307
27 University of Cincinnati Cincinnatti Ohio United States 45267
28 Dayton Heart Center Dayton Ohio United States 45414
29 The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield Fairfield Ohio United States 45014
30 Oklahoma Heart Hospital Oklahoma City Oklahoma United States 73120
31 Drexel University College of Medicine Philadelphia Pennsylvania United States 19102
32 Memorial Hospital of RI Pawtucket Rhode Island United States 02860
33 The Miriam Hosptial Providence Rhode Island United States 02906
34 University of Texas Health Science Center Houston Texas United States 77030
35 The Heart Hospital Baylor Plano - Research Insititute Plano Texas United States 75024
36 CV Group Central Lynchburg/Stroobants Heart Center Lynchburg Virginia United States 25401
37 University of Wisconsin Madison Wisconsin United States 53792

Sponsors and Collaborators

  • Cardiovascular Clinical Science Foundation

Investigators

  • Principal Investigator: Marvin Konstam, MD, Cardiovascular Clinical Science Foundation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Cardiovascular Clinical Science Foundation
ClinicalTrials.gov Identifier:
NCT01584557
Other Study ID Numbers:
  • CCSF-2011-001
First Posted:
Apr 25, 2012
Last Update Posted:
Sep 27, 2016
Last Verified:
Aug 1, 2016
Additional relevant MeSH terms:
Heart Failure
Tolvaptan

Study Results

No Results Posted as of Sep 27, 2016