AiDing Diuresis wIth Tolvaptan (ADD-IT)

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).

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