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

NCT01584557 | Completed Phase 3 DMC

• 1 other identifier: CCSF-2011-001
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 37

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (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.

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

  8 and 16 hours

Secondary Outcomes (6)

• 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.

  up to 7 days.

• 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

  30 days.

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

  at 48 hours or dischage, whichever comes first

Study Arms (2)

Tolvaptan, Samsca

ACTIVE COMPARATOR

Tolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days.

Drug: Tolvaptan or Samsca

sugar pill

PLACEBO COMPARATOR

placebo, sugar pill

Drug: placebo or sugar pill

Interventions

Tolvaptan or Samsca DRUG

uncoated tablet, 30mg, once per day, for up to 7 days.

Tolvaptan, Samsca

placebo or sugar pill DRUG

sugar pill

sugar pill

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• Positive urine pregnancy test for women of child bearing potential.
• Inability to provide written informed consent.
• Cardiac surgery within 60 days prior to study randomization.
• Acute Coronary Syndrome (ACS) or percutaneous coronary intervention within 30 days prior to study randomization.
• Planned revascularization procedures, cardiac mechanical support implantation, cardiac transplantation, or other cardiac surgery within 30 days following study randomization.
• Planned electrophysiologic (EP) device implantation within 7 days following study randomization.
• Subjects who are on cardiac mechanical support.
• Co-morbid condition with an expected survival less than six months.
• History of a cerebrovascular accident within the last 30 days.
• Hemodynamically significant uncorrected primary cardiac valvular disease.
• Hypertrophic cardiomyopathy (obstructive or non-obstructive).
• Uncorrected thyroid disease, active myocarditis or known amyloid cardiomyopathy.
• History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
• Chronic uncontrolled diabetes mellitus as determined by the investigator.
• Supine systolic arterial blood pressure \< 90 mmHg.

Sponsors & Collaborators

• Cardiovascular Clinical Sciences Inc: lead

Study Sites (37)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

The Heart Center Research

Huntsville, Alabama, 35801, United States

Location

Greater Los Angeles VA Medical Center

Los Angeles, California, 90073, United States

Location

University of Florida Health Science Ctr. Jacksonville

Jacksonville, Florida, 32209, United States

Location

MIMA Century Research Associates

Melbourne, Florida, 32901, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University Cardiology Associates, LLC

Augusta, Georgia, 30901, United States

Location

Mercer University School of Medicine

Macon, Georgia, 31201, United States

Location

Advocate Medical Group - Oakbrook

Naperville, Illinois, 60540, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

St. Vincent Medical Group

Indianapolis, Indiana, 46260, United States

Location

CardioSpecialists Group

Munster, Indiana, 46321, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Advanced Cardiovascular Specialists

Shreveport, Louisiana, 71135, United States

Location

Louisiana Heart Center and Research

Slidell, Louisiana, 70458, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

Location

Crittenton Hospital Medical Center

Rochester, Michigan, 48307, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

Bryan Heart Institute

Lincoln, Nebraska, 68506, United States

Location

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

Caromont Heart/Gaston Memorial Hospital

Gastonia, North Carolina, 28054, United States

Location

Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente

Lumberton, North Carolina, 28358, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

University of Cincinnati

Cincinnatti, Ohio, 45267, United States

Location

Dayton Heart Center

Dayton, Ohio, 45414, United States

Location

The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield

Fairfield, Ohio, 45014, United States

Location

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, 73120, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Memorial Hospital of RI

Pawtucket, Rhode Island, 02860, United States

Location

The Miriam Hosptial

Providence, Rhode Island, 02906, United States

Location

University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

The Heart Hospital Baylor Plano - Research Insititute

Plano, Texas, 75024, United States

Location

CV Group Central Lynchburg/Stroobants Heart Center

Lynchburg, Virginia, 25401, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 28302292 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Tolvaptan; Sugars

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Marvin Konstam, MD

  Cardiovascular Clinical Sciences Inc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2012
• First Posted: April 25, 2012
• Study Start: June 1, 2012
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: September 27, 2016

Record last verified: 2016-08

Locations

US (37)