AiDing Diuresis wIth Tolvaptan (ADD-IT)

Sponsor

Emory University (Other)

Overall Status

Completed

CT.gov ID

NCT02646540

Collaborator

(none)

Enrollment

Locations

Arms

35.9

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test the use of tolvaptan (commercial name Samsca) when given in addition to intravenous (IV) diuretics early during an episode of acute heart failure. It will be compared to a high dose of IV diuretics alone or the use of metolazone in addition to IV diuretics. The investigators are looking to see if there is improvement in the symptoms and outcomes of persons with acute heart failure.

Condition or Disease	Intervention/Treatment	Phase
Cardiomyopathy Congestive Heart Failure	Drug: Tolvaptan 30 mg + IV Diuretics Drug: Metolazone 5 mg + IV Diuretics Drug: 2.5 times the Diuretics Dose	Phase 1

Detailed Description

This is a single-center, randomized trial to assess the effects of 30 mg daily of tolvaptan when given concomitantly with home dose of diuretic (Lasix equivalent) intravenously (IV) versus 5mg daily of metolazone given concomitantly with home dose of diuretic (Lasix equivalent) IV, versus 2.5 times home dose of diuretic (Lasix equivalent) IV in participants hospitalized for acutely decompensated heart failure (ADHF).

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

AiDing Diuresis wIth Tolvaptan (ADD-IT)

Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Dec 30, 2018

Actual Study Completion Date :

Dec 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tolvaptan 30 mg and IV Lasix Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 30 mg of tolvaptan concomitantly with their standard dose of diuretics.	Drug: Tolvaptan 30 mg + IV Diuretics Participants will receive oral daily tolvaptan 30 mg concomitantly with their standard dose of intravenous (IV) diuretics for the duration of their hospitalization. Other Names: Tolvaptan (Samsca) and Lasix (Furosemide)
Active Comparator: Metolazone 5mg and IV Lasix Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 5mg metolazone concomitantly with their standard dose of diuretics.	Drug: Metolazone 5 mg + IV Diuretics Participants will receive oral daily metolazone 5 mg concomitantly with their standard dose of intravenous (IV) diuretics for the duration of their hospitalization. Other Names: Metolazone (Zaroxolyn) and Lasix (Furosemide)
Active Comparator: IV Lasix Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive two and a half (2.5) times their standard dose of diuretics.	Drug: 2.5 times the Diuretics Dose Participants will receive two and a half (2.5) times their standard dose of intravenous (IV) diuretics for the duration of their hospitalization. Other Names: Lasix (Furosemide)

Arm

Intervention/Treatment

Experimental: Tolvaptan 30 mg and IV Lasix

Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 30 mg of tolvaptan concomitantly with their standard dose of diuretics.

Drug: Tolvaptan 30 mg + IV Diuretics

Participants will receive oral daily tolvaptan 30 mg concomitantly with their standard dose of intravenous (IV) diuretics for the duration of their hospitalization.

Other Names:

Tolvaptan (Samsca) and Lasix (Furosemide)

Active Comparator: Metolazone 5mg and IV Lasix

Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 5mg metolazone concomitantly with their standard dose of diuretics.

Drug: Metolazone 5 mg + IV Diuretics

Participants will receive oral daily metolazone 5 mg concomitantly with their standard dose of intravenous (IV) diuretics for the duration of their hospitalization.

Other Names:

Metolazone (Zaroxolyn) and Lasix (Furosemide)

Active Comparator: IV Lasix

Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive two and a half (2.5) times their standard dose of diuretics.

Drug: 2.5 times the Diuretics Dose

Participants will receive two and a half (2.5) times their standard dose of intravenous (IV) diuretics for the duration of their hospitalization.

Other Names:

Lasix (Furosemide)

Outcome Measures

Primary Outcome Measures

Length of Hospitalization Measured in Days [Duration of Hospitalization (Average of Five Days)]
The number of days hospitalized until discharge.

Secondary Outcome Measures

Change in Body Weight [Baseline (hospital admission), Discharge (Average of 5 Days)]
The difference in body weight from hospital admission to discharge measured in kilograms.
Total Diuretic Dose [Up to Five Days]
The total dose of diuretics given throughout the duration of hospitalization measured in milligrams (mg).
Change in estimated glomerular filtration rate (eGFR) [Baseline (hospital admission), Discharge (Average of 5 days)]
The difference in eGFR from baseline (hospital admission) to discharge.
Number of Days Alive [Post Hospital Discharge (30 days)]
The number of days participants remain alive over thirty days after hospital discharge.
Rate of Re-Hospitalization [30 Days Post Hospitalization]
The number of participants re-hospitalized for worsening heart failure or death at 30 days.
Number of Electrolyte Imbalance Related Adverse Events [Duration of Hospitalization (Average of Five Days)]
The number of adverse events due to electrolyte imbalance throughout the duration of hospitalization.
Number of Participants Requiring Electrolyte Repletion [Duration of Hospitalization (Average of Five Days)]
The number of participants that require electrolyte repletion throughout the duration of hospitalization.
Change in Sodium Level [Baseline (hospital admission), Discharge (Average of 5 days)]
The difference in sodium levels from baseline to hospital discharge measured in milliequivalents per liter (mEqL).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants hospitalized for worsening acute heart failure and randomized within 36 hours of initial presentation
New York Heart Association (NYHA) Class III or IV on admission to the hospital with at least 1 month history of treated heart failure
Able to understand content of and willing to provide written informed consent

The participant must have signs of extracellular volume expansion, defined as two or more of the following four signs or symptoms:

signs of RHF (right heart failure) (jugular venous distention, pitting edema, or (≥1+), ascites and/or signs of LHF (left heart failure) (pulmonary congestion on chest x-ray, pulmonary rales)
Brain Natriuretic Peptide (BNP) > 450
serum sodium < 140 mEq/L

Exclusion Criteria:

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
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, defined as 3x upper limit of normal (ULN)
Chronic uncontrolled diabetes mellitus with Hemoglobin A1C > 10%
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