Heart FailurePhase 3Secret of CHFNCT01584557
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
A Phase 3 study testing Tolvaptan or Samsca in people with Heart Failure, run by Cardiovascular Clinical Sciences Inc at 37 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Tolvaptan or Samsca
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 250 participants
- Where
- 37 sitesUnited States
- Study dates
- Jun 2012to Aug 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
- Serum creatinine > 3.5 mg/dL or undergoing dialysis.
- Hemoglobin < 9 g/dL
- History of hypersensitivity and/or idiosyncratic reaction to benzazepine derivatives (such as benazepril).
- Inability to take oral medications.
- 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.
- Previous exposure to tolvaptan within 7 days prior to randomization.
- 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.
- Ultrafiltration within 7 days prior to randomization or planned.
- Active gout
- Serum sodium >144 mEq/L
Trial locations and contacts
37 sites in 1 country.
37 sites in 1 country
United States37 sites
Akron General Medical Center
Akron, Ohio, 44307
Emory University
Atlanta, Georgia, 30322
University Cardiology Associates, LLC
Augusta, Georgia, 30901
University of Maryland
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Tufts Medical Center
Boston, Massachusetts, 02111
Lahey Hospital and Medical Center
Burlington, Massachusetts, 01805
University of Cincinnati
Cincinnatti, Ohio, 45267
Dayton Heart Center
Dayton, Ohio, 45414
The Sisters of Mercy of Hamilton, Ohio dba Mercy Hospital Fairfield
Fairfield, Ohio, 45014
Caromont Heart/Gaston Memorial Hospital
Gastonia, North Carolina, 28054
University of Texas Health Science Center
Houston, Texas, 77030
The Heart Center Research
Huntsville, Alabama, 35801
St. Vincent Medical Group
Indianapolis, Indiana, 46260
University of Florida Health Science Ctr. Jacksonville
Jacksonville, Florida, 32209
Bryan Heart Institute
Lincoln, Nebraska, 68506
Greater Los Angeles VA Medical Center
Los Angeles, California, 90073
Duke Cardiology of Lumberton Research/Southeastern Regional Medical Cente
Lumberton, North Carolina, 28358
CV Group Central Lynchburg/Stroobants Heart Center
Lynchburg, Virginia, 25401
Mercer University School of Medicine
Macon, Georgia, 31201
University of Wisconsin
Madison, Wisconsin, 53792
MIMA Century Research Associates
Melbourne, Florida, 32901
Jackson Memorial Hospital
Miami, Florida, 33136
Minneapolis Heart Institute
Minneapolis, Minnesota, 55407
CardioSpecialists Group
Munster, Indiana, 46321
Advocate Medical Group - Oakbrook
Naperville, Illinois, 60540
Ochsner Medical Center
New Orleans, Louisiana, 70121
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453
Oklahoma Heart Hospital
Oklahoma City, Oklahoma, 73120
Memorial Hospital of RI
Pawtucket, Rhode Island, 02860
Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
The Heart Hospital Baylor Plano - Research Insititute
Plano, Texas, 75024
The Miriam Hosptial
Providence, Rhode Island, 02906
The Valley Hospital
Ridgewood, New Jersey, 07450
Crittenton Hospital Medical Center
Rochester, Michigan, 48307
Advanced Cardiovascular Specialists
Shreveport, Louisiana, 71135
Louisiana Heart Center and Research
Slidell, Louisiana, 70458
About this study
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
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
- Being tested
- Tolvaptan or Samsca, placebo or sugar pill
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolvaptan or SamscaDrug
uncoated tablet, 30mg, once per day, for up to 7 days.
placebo or sugar pillDrug
sugar pill
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan, Samsca | Active comparator | Tolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days. Receives: Drug: Tolvaptan or Samsca |
| sugar pill | Placebo comparator | placebo, sugar pill Receives: Drug: placebo or sugar pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 8 and 16 hours
Secondary outcomes (6)
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.
Measured: up to 7 days
Diuretic dose measured daily while hospitalized up to 7 days.
Diuretic dose measured daily while hospitalized up to 7 days.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 30 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2012 (estimated)
- Study startJun 2012
- Primary completionJul 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 250 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cardiovascular Clinical Sciences Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Marvin Konstam, MD, Principal investigator, Cardiovascular Clinical Sciences Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01584557
- Sponsor's protocol ID
- CCSF-2011-001
- Acronym
- Secret of CHF
- Status last verified
- Aug 2016
- First submitted
- 10 Apr 2012
- Last updated
- 27 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 28302292
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01584557
- Acronym / sponsor ID
- Secret of CHF / CCSF-2011-001
- Conditions
- Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 250 participants (actual)
- Lead sponsor
- Cardiovascular Clinical Sciences IncIndustry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 25 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan, Samsca | Active comparator | Drug: Tolvaptan or SamscaTolvaptan, Samsca, uncoated tablet, 30 mg, once per day, up to 7 days. |
| sugar pill | Placebo comparator | Drug: placebo or sugar pillplacebo, sugar pill |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tolvaptan or Samscauncoated tablet, 30mg, once per day, for up to 7 days. | Drug | Tolvaptan, Samsca |
| placebo or sugar pillsugar pill | Drug | sugar pill |
Primary outcome
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.
6 secondary outcomes
Change from baseline in body weight measured daily while hospitalized up to 7 days.
Time frame: up to 7 days
Diuretic dose measured daily while hospitalized up to 7 days.
Time frame: 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.
Days alive and out of the hospital over 30 days
Time frame: 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
Re-hospitalization for worsening heart failure or death at 30 days
Time frame: 30 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2016.
- Derived from this study: PubMed 28302292Konstam 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marvin Konstam, MD principal investigator
Cardiovascular Clinical Sciences Inc
37 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan or Samsca in people with Heart Failure, run by Cardiovascular Clinical Sciences Inc at 37 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01584557, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016.