Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure (TACTICS-HF)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT01644331 |
|
Recruitment Status :
Completed
First Posted : July 19, 2012
Results First Posted : April 27, 2017
Last Update Posted : April 27, 2017
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
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
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Heart Failure Dyspnea | Drug: Tolvaptan Drug: Placebo | Phase 3 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 257 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study |
| Study Start Date : | October 2012 |
| Actual Primary Completion Date : | February 2016 |
| Actual Study Completion Date : | February 2016 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Tolvaptan
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)
|
Drug: Tolvaptan
IV furosemide plusTolvaptan (given at 0, 24 and 48 hours)
Other Name: Samsca |
|
Placebo Comparator: Placebo
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)
|
Drug: Placebo
IV furosemide plus oral placebo (given at 0, 24 and 48 hours) |
- 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.
- Renal Function [ Time Frame: 0, 24, 48 and 72 hours ]Change in Serum creatinine from baseline to 24, 48 and 72 hours
- Weight Loss [ Time Frame: 0, 24, 48, and 72 hours ]Change in body weight from baseline to 24, 48, and 72 hours
- Fluid Loss [ Time Frame: 0, 24, 48, and 72 hours ]Change from baseline fluid balance at 24, 48, and 72 hours
- Dyspnea Likert [ Time Frame: 48 and 72 hours ]Number of patients that experience moderate or greater improvement (patient reported) in dyspnea by 7 point Likert scale at 48 and 72 hours
- Hospital Stay [ Time Frame: 7 days ]Total days spent in hospital from baseline until discharge or death
- Worsening or Persistent Heart Failure or Death [ Time Frame: 72 hrs ]Number of patients with worsening heart failure or death
- Over-diuresis [ Time Frame: 72 hours ]clinical evidence of volume depletion requiring intervention other than holding diuretics during the 72 hours after randomization
- Serum Sodium [ Time Frame: 0, 24, 48, and 72 hours ]Change in serum sodium from baseline to 24, 48, and 72 hours
- Dyspnea 11 Point NRS [ Time Frame: 0, 24, 48, and 72 hours ]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)
- Freedom From Congestion [ Time Frame: 24, 48, and 72 hours ]Jugular Venous Pressure (JVP) < 8 cm, no orthopnea, trace peripheral edema or less, and will be assessed at 24, 48, and 72 hours
- Development of Worsening Renal Function [ Time Frame: 72 hours ]increase in serum creatinine ≥ 0.3mg/dl from randomization at any time point during 72 hours after randomization
- Days Hospitalized or Deceased [ Time Frame: 30 days ]Total days hospitalized or deceased during the 30 days after randomization
- All Cause Death or Rehospitalization [ Time Frame: 30 days ]All cause death or rehospitalization (to include unscheduled clinic visits or ED visits) at 30 days (Kaplan-Meier and 95% confidence interval)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- ≥ 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
- 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
Exclusion Criteria:
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01644331
Show 18 study locations
| Principal Investigator: | Michael Felker, MD | Duke Clinical Research Institute |
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT01644331 |
| Other Study ID Numbers: |
Pro00037557 |
| First Posted: | July 19, 2012 Key Record Dates |
| Results First Posted: | April 27, 2017 |
| Last Update Posted: | April 27, 2017 |
| Last Verified: | March 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Plan Description: | Not yet decided. |
|
Dyspnea Heart Failure Heart Diseases Cardiovascular Diseases Respiration Disorders Respiratory Tract Diseases |
Signs and Symptoms, Respiratory Tolvaptan Antidiuretic Hormone Receptor Antagonists Molecular Mechanisms of Pharmacological Action Natriuretic Agents Physiological Effects of Drugs |