Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure

Heart Failure Clinical Trial

— TACTICS-HF  

Official title:

The Targeting Acute Congestion With Tolvaptan In Congestive Heart Failure Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01644331
• Other study ID #: Pro00037557
• Status: Completed
• Phase: Phase 3
• First received: July 17, 2012
• Last updated: March 10, 2016
• Start date: October 2012
• Est. completion date: February 2016

Study information

• Verified date: March 2016
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Data and Safety Monitoring BoardUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see if taking tolvaptan by mouth in addition to the regular treatment received for shortness of breath due to heart failure will work better than the regular treatment alone. The study will also look to see if other symptoms of heart failure or problems associated with heart failure treatments, like changes in kidney function, are affected by tolvaptan.

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.

Description:

This study will be a randomized, double blind, placebo controlled, multi-center clinical trial of patients with signs and symptoms consistent with acute heart failure (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 every 12 hours or 40 mg IV Q12 hours, whichever is greater + oral Tolvaptan (given at 0, 12, 24 and 48 hours)

• Fixed-dose IV furosemide (1 x total daily oral dose) given intravenously in divided doses every 12 hours or 40 mg IV Q12 hours, whichever is greater + oral placebo (given at 0, 12, 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 257
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Dyspnea
• Heart Failure

Intervention

Drug:
• Tolvaptan
Tolvaptan (given at 0, 12, 24 and 48 hours)
• Placebo
IV furosemide (1 x oral dose given IV in Q12 hours divided doses) plus oral placebo (given at 0, 12, 24 and 48 hours)

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Hennepin County Medical Center	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dyspnea improvement measured by Likert scale at 8 and 24 hours	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.	24 hours	No
Secondary	Renal function	Change from baseline blood urea nitrogen (BUN) at Day 7 or discharge Change from baseline serum creatinine at Day 7 or discharge	7 days	Yes
Secondary	Body weight	Change from baseline body weight at Day 7 or discharge	7 days	Yes
Secondary	Fluid Loss	Change from baseline fluid balance at Day 7 or discharge Change from baseline serum sodium at Day 7 or discharge	7 days	Yes
Secondary	Breathing	Change from baseline dyspnea at 72 hours	3 days	Yes
Secondary	Hospital stay	Total days spent in hospital from baseline until discharge or death	7 days	No
Secondary	worsening heart failure	Change from baseline heart failure assessment at Day 7 or discharge	7 days	Yes