AiDing Diuresis wIth Tolvaptan (ADD-IT)

Phase 1

Completed

• Conditions: Cardiomyopathy; Congestive Heart Failure
• Interventions: Drug: Tolvaptan 30 mg + IV Diuretics; Drug: Metolazone 5 mg + IV Diuretics; Drug: 2.5 times the Diuretics Dose

• Registration Number: NCT02646540
• Lead Sponsor: Emory University

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.

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 Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-04
• Study First Submitted QC: 2016-01-04
• Study First Posted: 2016-01-05
• Primary Completion: 2018-12-30
• Study Completion: 2018-12-30
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-25
• Last Update Posted: 2019-03-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tolvaptan 30 mg and IV Lasix	Tolvaptan 30 mg + IV Diuretics	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.
Metolazone 5mg and IV Lasix	Metolazone 5 mg + IV Diuretics	Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 5mg metolazone concomitantly with their standard dose of diuretics.
IV Lasix	2.5 times the Diuretics Dose	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.

Primary Outcome Measures

Name	Time	Method
Length of Hospitalization Measured in Days	Duration of Hospitalization (Average of Five Days)	The number of days hospitalized until discharge.

Secondary Outcome Measures

Name	Time	Method
Rate of Re-Hospitalization	30 Days Post Hospitalization	The number of participants re-hospitalized for worsening heart failure or death at 30 days.
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.
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).

Trial Locations

Locations (2)

Emory University Hospital Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States