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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tolvaptan, Samsca | Active Comparator | Tolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days. |
|
| sugar pill | Placebo Comparator | placebo, sugar pill |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tolvaptan or Samsca | Drug | uncoated tablet, 30mg, once per day, for up to 7 days. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 and 16 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in body weight measured daily while hospitalized up to 7 days. | Change from baseline in body weight measured daily while hospitalized up to 7 days. | up to 7 days |
| Diuretic dose measured daily while hospitalized up to 7 days. |
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Inclusion Criteria:
Subjects hospitalized for worsening heart failure and randomized within 36 hours of initial presentation.
Males and females 18 years of age or older.
NYHA Class III or IV on admission to the hospital.
Able to understand content of and willing to provide written informed consent
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.
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)
Have at least one of the following:
Time Period (hr) Cumulative UO (mL) 2 <250 3 <375 4 <500 5 <625 6 <750 7 <875 8 <1000
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marvin Konstam, MD | Cardiovascular Clinical Sciences Inc | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| The Heart Center Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28302292 | Derived | Konstam MA, Kiernan M, Chandler A, Dhingra R, Mody FV, Eisen H, Haught WH, Wagoner L, Gupta D, Patten R, Gordon P, Korr K, Fileccia R, Pressler SJ, Gregory D, Wedge P, Dowling D, Romeling M, Konstam JM, Massaro JM, Udelson JE; SECRET of CHF Investigators, Coordinators, and Committee Members. Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol. 2017 Mar 21;69(11):1409-1419. doi: 10.1016/j.jacc.2016.12.035. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jun 2, 2017 | |
| Reset | Jun 22, 2017 | |
| Release | Jul 10, 2017 |
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| placebo or sugar pill |
| Drug |
sugar pill |
|
Diuretic dose measured daily while hospitalized up to 7 days.
| up to 7 days. |
| Change from baseline in estimated glomerular filtration rate (eGFR) 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. | at discharge or day 7, whichever comes first. |
| Days alive and out of the hospital over 30 days | Days alive and out of the hospital over 30 days | 30 days. |
| Change from baseline in cognitive function at 48 hours or discharge, whichever comes first | Change from baseline in cognitive function at 48 hours or discharge, whichever comes first | at 48 hours or dischage, whichever comes first |
| Re-hospitalization for worsening heart failure or death at 30 days | Re-hospitalization for worsening heart failure or death at 30 days | 30 days. |
| Huntsville |
| Alabama |
| 35801 |
| United States |
| Greater Los Angeles VA Medical Center | Los Angeles | California | 90073 | United States |
| University of Florida Health Science Ctr. Jacksonville | Jacksonville | Florida | 32209 | United States |
| MIMA Century Research Associates | Melbourne | Florida | 32901 | United States |
| Jackson Memorial Hospital | Miami | Florida | 33136 | United States |
| Emory University | Atlanta | Georgia | 30322 | United States |
| University Cardiology Associates, LLC | Augusta | Georgia | 30901 | United States |
| Mercer University School of Medicine | Macon | Georgia | 31201 | United States |
| Advocate Medical Group - Oakbrook | Naperville | Illinois | 60540 | United States |
| Advocate Christ Medical Center | Oak Lawn | Illinois | 60453 | United States |
| St. Vincent Medical Group | Indianapolis | Indiana | 46260 | United States |
| CardioSpecialists Group | Munster | Indiana | 46321 | United States |
| Ochsner Medical Center | New Orleans | Louisiana | 70121 | United States |
| Advanced Cardiovascular Specialists | Shreveport | Louisiana | 71135 | United States |
| Louisiana Heart Center and Research | Slidell | Louisiana | 70458 | United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| Tufts Medical Center | Boston | Massachusetts | 02111 | United States |
| Lahey Hospital and Medical Center | Burlington | Massachusetts | 01805 | United States |
| Crittenton Hospital Medical Center | Rochester | Michigan | 48307 | United States |
| Minneapolis Heart Institute | Minneapolis | Minnesota | 55407 | United States |
| Bryan Heart Institute | Lincoln | Nebraska | 68506 | United States |
| The Valley Hospital | Ridgewood | New Jersey | 07450 | United States |
| Caromont Heart/Gaston Memorial Hospital | Gastonia | North Carolina | 28054 | United States |
| Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente | Lumberton | North Carolina | 28358 | United States |
| Akron General Medical Center | Akron | Ohio | 44307 | United States |
| University of Cincinnati | Cincinnatti | Ohio | 45267 | United States |
| Dayton Heart Center | Dayton | Ohio | 45414 | United States |
| The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield | Fairfield | Ohio | 45014 | United States |
| Oklahoma Heart Hospital | Oklahoma City | Oklahoma | 73120 | United States |
| Drexel University College of Medicine | Philadelphia | Pennsylvania | 19102 | United States |
| Memorial Hospital of RI | Pawtucket | Rhode Island | 02860 | United States |
| The Miriam Hosptial | Providence | Rhode Island | 02906 | United States |
| University of Texas Health Science Center | Houston | Texas | 77030 | United States |
| The Heart Hospital Baylor Plano - Research Insititute | Plano | Texas | 75024 | United States |
| CV Group Central Lynchburg/Stroobants Heart Center | Lynchburg | Virginia | 25401 | United States |
| University of Wisconsin | Madison | Wisconsin | 53792 | United States |
| Reset | Aug 10, 2017 |
| Release | Jan 30, 2019 |
| Reset | Feb 19, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jun 2, 2017 | Jun 22, 2017 | |||
| Jul 10, 2017 | Aug 10, 2017 | |||
| Jan 30, 2019 | Feb 19, 2019 |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000077602 | Tolvaptan |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D002241 | Carbohydrates |
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