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)

September 26, 2016 updated by: Cardiovascular Clinical Science Foundation

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
250

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
      • Huntsville, Alabama, United States, 35801
        • The Heart Center Research
    • California
      • Los Angeles, California, United States, 90073
        • Greater Los Angeles VA Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Science Ctr. Jacksonville
      • Melbourne, Florida, United States, 32901
        • MIMA Century Research Associates
      • Miami, Florida, United States, 33136
        • Jackson Memorial Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
      • Augusta, Georgia, United States, 30901
        • University Cardiology Associates, LLC
      • Macon, Georgia, United States, 31201
        • Mercer University School of Medicine
    • Illinois
      • Naperville, Illinois, United States, 60540
        • Advocate Medical Group - Oakbrook
      • Oak Lawn, Illinois, United States, 60453
        • Advocate Christ Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • St. Vincent Medical Group
      • Munster, Indiana, United States, 46321
        • CardioSpecialists Group
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
      • Shreveport, Louisiana, United States, 71135
        • Advanced Cardiovascular Specialists
      • Slidell, Louisiana, United States, 70458
        • Louisiana Heart Center and Research
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital and Medical Center
    • Michigan
      • Rochester, Michigan, United States, 48307
        • Crittenton Hospital Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Minneapolis Heart Institute
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Bryan Heart Institute
    • New Jersey
      • Ridgewood, New Jersey, United States, 07450
        • The Valley Hospital
    • North Carolina
      • Gastonia, North Carolina, United States, 28054
        • Caromont Heart/Gaston Memorial Hospital
      • Lumberton, North Carolina, United States, 28358
        • Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente
    • Ohio
      • Akron, Ohio, United States, 44307
        • Akron General Medical Center
      • Cincinnatti, Ohio, United States, 45267
        • University of Cincinnati
      • Dayton, Ohio, United States, 45414
        • Dayton Heart Center
      • Fairfield, Ohio, United States, 45014
        • The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73120
        • Oklahoma Heart Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
    • Rhode Island
      • Pawtucket, Rhode Island, United States, 02860
        • Memorial Hospital of RI
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hosptial
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas Health Science Center
      • Plano, Texas, United States, 75024
        • The Heart Hospital Baylor Plano - Research Insititute
    • Virginia
      • Lynchburg, Virginia, United States, 25401
        • CV Group Central Lynchburg/Stroobants Heart Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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.
Time Frame: 8 and 16 hours
The primary variable for assessing efficacy will be self-assessed 7-point dyspnea score at 8 and 16 hours.
8 and 16 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline in body weight measured daily while hospitalized up to 7 days.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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
Time Frame: 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
Time Frame: at 48 hours or dischage, 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
Time Frame: 30 days.
Re-hospitalization for worsening heart failure or death at 30 days
30 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cardiovascular Clinical Science Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marvin Konstam, MD, Cardiovascular Clinical Science Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2012

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 10, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 23, 2012

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 25, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 27, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 26, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CCSF-2011-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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