AiDing Diuresis wIth Tolvaptan (ADD-IT) (ADD-IT)

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.

Study Overview

• Status: Completed
• Conditions: Congestive Heart Failure; Cardiomyopathy
• Intervention / Treatment: Drug: Tolvaptan 30 mg + IV Diuretics; Drug: Metolazone 5 mg + IV Diuretics; Drug: 2.5 times the Diuretics Dose

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospitalization Measured in Days	The number of days hospitalized until discharge.	Duration of Hospitalization (Average of Five Days)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Emory University
• Investigators: Principal Investigator: Divya Gupta, MD, Emory University

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (ACTUAL): December 30, 2018
• Study Completion (ACTUAL): December 30, 2018

Study Registration Dates

• First Submitted: January 4, 2016
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (ESTIMATE): January 5, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Cardiomyopathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Antidiuretic Hormone Receptor Antagonists; Furosemide; Diuretics; Tolvaptan; Metolazone
• Other Study ID Numbers: IRB00080051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No