Heart FailurePhase 3TACTICS-HFNCT01644331
Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure
A Phase 3 study testing Tolvaptan in people with Heart Failure and Dyspnea, run by Duke University at 18 sites in United States.
Trial summary
The primary objective of this study is to compare the effects of oral Tolvaptan vs. placebo as an adjunct to fixed dose IV furosemide on dyspnea relief in patients with acute decompensated heart failure The primary hypothesis is that the addition of oral Tolvaptan to fixed dose furosemide will be more effective at… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Dyspnea
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 257 participants
- Where
- 18 sitesUnited States
- Study dates
- Oct 2012to Feb 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- ≥ 18 years of age
- Daily oral dose of furosemide between ≥ 40 mg(or equivalent)
- Identified within 24 hours of presentation, defined for purposes of this study as the time of initial dose of intravenous loop diuretic
- Prior clinical HF diagnosis that was treated with oral loop diuretics for at least 1 month
- Admission for acute decompensated Heart Failure (HF) as determined by
- dyspnea at rest or with minimal exertion
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- Brain Natriuretic Peptide (BNP) > 400 or NTproBNP > 2000 pg/mL
- AND at least one of the following additional signs and symptoms:
- Orthopnea
- Peripheral edema
- Elevated JVP (Jugular Venous Pressure)
- Pulmonary rales
- Congestion on Chest X-ray
- No plan for revascularization, cardiac transplant, of ventricular assist device implantation, or other cardiac surgery within 60 days of randomization
- Signed informed consent
Who cannot join
- Serum Na > 140 meq/L
- Received IV vasoactive treatment or ultra-filtration therapy for HF since initial presentation
- Treatment plan during current hospitalization includes IV vasoactive treatment or ultra-filtration for HF
- Systolic Blood Pressure (SBP)<90mmHg
- Serum-Cr>3.5mg/dl or currently undergoing renal replacement therapy
- . Known underlying liver disease
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- Hemodynamically significant arrhythmias
- ACS(Acute coronary syndrome) within 4 weeks prior to study entry
- Active myocarditis
- Hypertrophic obstructive, restrictive, constrictive cardiomyopathy
- Severe stenotic valvular disease
- Complex congenital heart disease
- Constrictive pericarditis
- Clinical evidence of digoxin toxicity
- Need for mechanical hemodynamic support
- Terminal illness (other than heart failure) with expected survival time of less than 1 year
- History of adverse reaction to Tolvaptan
- Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
- Pregnant or breast-feeding
- Inability to comply with planned study procedures
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Colorado at Denver and Health Sciences Center
Aurora, Colorado, 80045
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
Novant Health Heart and Vascular
Charlotte, North Carolina, 28204
University of Chicago
Chicago, Illinois, 60637
The Christ Hospital
Cincinnati, Ohio, 45219
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
UT Southwestern Medical center
Dallas, Texas, 75390
Duke University Medical Center
Durham, North Carolina, 27713
Inova Heart and Vascular Institute
Falls Church, Virginia, 22042
Northeast Georgia Heart Center
Gainesville, Georgia, 30501
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Southeastern Regional Medical Center
Lumberton, North Carolina, 28358
Mercer University School of Medicine
Macon, Georgia, 31201
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Allegheny Valley Hospital
Natrona Heights, Pennsylvania, 15065
Grand View - Lehigh Valley Health Services
Sellersville, Pennsylvania, 18960
Montefiore Medical Center
The Bronx, New York, 10461
About this study
Official title: The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study
The primary objective of this study is to compare the effects of oral Tolvaptan vs. placebo as an adjunct to fixed dose IV furosemide on dyspnea relief in patients with acute decompensated heart failure
The primary hypothesis is that the addition of oral Tolvaptan to fixed dose furosemide will be more effective at relieving dyspnea than fixed dose furosemide alone
Read the detailed description
This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with AHF within 24 hours of presentation at Emergency Department. A total of approximately 250 patients will be enrolled in the trial.
Patients will be randomized in a 1:1 ratio to either of 2 treatment regimens:
- Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours)
- Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours)
The study treatment regimen will be administered from randomization through 48 hours, at which point Tolvaptan/placebo will be discontinued and all diuretic treatment will be adjusted at the treating physician's discretion.
The primary endpoint will be the proportion of patients with at least moderate improvement in dyspnea by Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.
Patients will be followed daily for the duration of hospitalization or for 7 days (whichever is shortest).
All patients will have Day 30 follow up phone contact for assessment of vital status and interval hospitalizations.
- Conditions
- Heart Failure, Dyspnea
- Being tested
- Tolvaptan, Placebo
- Medical subject headings
- Heart Failure, Dyspnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called Samsca
IV furosemide plusTolvaptan (given at 0, 24 and 48 hours)
PlaceboDrug
IV furosemide plus oral placebo (given at 0, 24 and 48 hours)
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Experimental | Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours) Receives: Drug: Tolvaptan |
| Placebo | Placebo comparator | Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
The number of patients with at least moderate improvement (as reported by patient) in dyspnea Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.
Measured: 8 and 24 hours
Secondary outcomes (13)
Renal Function
Change in Serum creatinine from baseline to 24, 48 and 72 hours
Measured: 0, 24, 48 and 72 hours
Weight Loss
Change in body weight from baseline to 24, 48, and 72 hours
Measured: 0, 24, 48, and 72 hours
Fluid Loss
Change from baseline fluid balance at 24, 48, and 72 hours
Measured: 0, 24, 48, and 72 hours
Dyspnea Likert
Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
Measured: 48 and 72 hours
Hospital Stay
Total days spent in hospital from baseline until discharge or death
Measured: 7 days
Worsening or Persistent Heart Failure or Death
Number of patients with worsening heart failure or death
Measured: 72 hrs
Over-diuresis
clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
Measured: 72 hours
Serum Sodium
Change in serum sodium from baseline to 24, 48, and 72 hours
Measured: 0, 24, 48, and 72 hours
Dyspnea 11 Point NRS
Change in NRS for assessment of dyspnea from baseline to 24, 48, and 72 hours (scale ranges from 0-No difficulty breathing to 10-Difficulty as bad as you can imagine)
Measured: 0, 24, 48, and 72 hours
Freedom From Congestion
Jugular Venous Pressure (JVP) < 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
Measured: 24, 48, and 72 hours
Development of Worsening Renal Function
increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
Measured: 72 hours
Days Hospitalized or Deceased
Total days hospitalized or deceased during the 30 days after randomization
Measured: 30 days
All Cause Death or Rehospitalization
All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)
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 posted19 Jul 2012 (estimated)
- Study startOct 2012
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 257 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Felker, MD, Principal investigator, Duke Clinical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01644331
- Sponsor's protocol ID
- Pro00037557
- Acronym
- TACTICS-HF
- Status last verified
- Mar 2017
- First submitted
- 17 Jul 2012
- Last updated
- 27 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: Not yet decided.
Publications
Felker GM, Mentz RJ, Cole RT, Adams KF, Egnaczyk GF, Fiuzat M, Patel CB, Echols M, Khouri MG, Tauras JM, Gupta D, Monds P, Roberts R, O'Connor CM. Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol. 2017 Mar 21;69(11):1399-1406. doi: 10.1016/j.jacc.2016.09.004. Epub 2016 Sep 18.
PubMed 27654854
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study
- ClinicalTrials.gov ID
- NCT01644331
- Acronym / sponsor ID
- TACTICS-HF / Pro00037557
- Conditions
- Heart Failure, Dyspnea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 257 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 19 Jul 2012 (estimated)
- Results
- Posted 27 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to compare the effects of oral Tolvaptan vs. placebo as an adjunct to fixed dose IV furosemide on dyspnea relief in patients with acute decompensated heart failure
The primary hypothesis is that the addition of oral Tolvaptan to fixed dose furosemide will be more effective at relieving dyspnea than fixed dose furosemide alone
Detailed description
This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with AHF within 24 hours of presentation at Emergency Department. A total of approximately 250 patients will be enrolled in the trial.
Patients will be randomized in a 1:1 ratio to either of 2 treatment regimens:
- Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours)
- Fixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours)
The study treatment regimen will be administered from randomization through 48 hours, at which point Tolvaptan/placebo will be discontinued and all diuretic treatment will be adjusted at the treating physician's discretion.
The primary endpoint will be the proportion of patients with at least moderate improvement in dyspnea by Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.
Patients will be followed daily for the duration of hospitalization or for 7 days (whichever is shortest).
All patients will have Day 30 follow up phone contact for assessment of vital status and interval hospitalizations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Experimental | Drug: TolvaptanFixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral Tolvaptan (given at 0, 24 and 48 hours) |
| Placebo | Placebo comparator | Drug: PlaceboFixed-dose IV furosemide (1 x total daily oral dose given intravenously in divided doses Q12 hours OR 40 mg IV Q12 hours, whichever is greater) + oral placebo (given at 0, 24 and 48 hours) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- ≥ 18 years of age
- Daily oral dose of furosemide between ≥ 40 mg(or equivalent)
- Identified within 24 hours of presentation, defined for purposes of this study as the time of initial dose of intravenous loop diuretic
- Prior clinical HF diagnosis that was treated with oral loop diuretics for at least 1 month
- Admission for acute decompensated Heart Failure (HF) as determined by
Key exclusion criteria (20 listed)
- Serum Na > 140 meq/L
- Received IV vasoactive treatment or ultra-filtration therapy for HF since initial presentation
- Treatment plan during current hospitalization includes IV vasoactive treatment or ultra-filtration for HF
- Systolic Blood Pressure (SBP)<90mmHg
- Serum-Cr>3.5mg/dl or currently undergoing renal replacement therapy
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 |
|---|---|---|
| TolvaptanAlso: SamscaIV furosemide plusTolvaptan (given at 0, 24 and 48 hours) | Drug | Tolvaptan |
| PlaceboIV furosemide plus oral placebo (given at 0, 24 and 48 hours) | Drug | Placebo |
Primary outcome
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours
Time frame: 8 and 24 hours
The number of patients with at least moderate improvement (as reported by patient) in dyspnea Likert scale at both 8 AND 24 hours AND without the need for escalation of therapy due to worsening heart failure (rescue therapy) or death within 24 hours.
13 secondary outcomes
Renal Function
Time frame: 0, 24, 48 and 72 hours
Weight Loss
Time frame: 0, 24, 48, and 72 hours
Fluid Loss
Time frame: 0, 24, 48, and 72 hours
Dyspnea Likert
Time frame: 48 and 72 hours
Hospital Stay
Time frame: 7 days
Worsening or Persistent Heart Failure or Death
Time frame: 72 hrs
Over-diuresis
Time frame: 72 hours
Serum Sodium
Time frame: 0, 24, 48, and 72 hours
Dyspnea 11 Point NRS
Time frame: 0, 24, 48, and 72 hours
Freedom From Congestion
Time frame: 24, 48, and 72 hours
Development of Worsening Renal Function
Time frame: 72 hours
Days Hospitalized or Deceased
Time frame: 30 days
All Cause Death or Rehospitalization
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27654854Felker GM, Mentz RJ, Cole RT, Adams KF, Egnaczyk GF, Fiuzat M, Patel CB, Echols M, Khouri MG, Tauras JM, Gupta D, Monds P, Roberts R, O'Connor CM. Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure. J Am Coll Cardiol. 2017 Mar 21;69(11):1399-1406. doi: 10.1016/j.jacc.2016.09.004. Epub 2016 Sep 18.
- Individual participant dataSharing planned: Undecided. Not yet decided.
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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.
Michael Felker, MD principal investigator
Duke Clinical Research Institute
18 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 in people with Heart Failure and Dyspnea, run by Duke University at 18 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 15 inclusion and 20 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 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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?
Yes. Results are posted in the registry (first posted 27 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Dyspnea Improvement Measured by Likert Scale at 8 and 24 Hours (time frame: 8 and 24 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 NCT01644331, 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 Apr 2017.