AiDing Diuresis wIth Tolvaptan (ADD-IT)

NCT02646540 | Completed Phase 1 FDA Drug

• 1 other identifier: IRB00080051
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

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.

Conditions

Cardiomyopathy; Congestive Heart Failure

Outcome Measures

Primary Outcomes (1)

• Length of Hospitalization Measured in Days

  The number of days hospitalized until discharge.

  Duration of Hospitalization (Average of Five Days)

Secondary Outcomes (8)

• Change in Body Weight

  Baseline (hospital admission), Discharge (Average of 5 Days)

• Total Diuretic Dose

  Up to Five Days

• Change in estimated glomerular filtration rate (eGFR)

  Baseline (hospital admission), Discharge (Average of 5 days)

• Number of Days Alive

  Post Hospital Discharge (30 days)

• Rate of Re-Hospitalization

  30 Days Post Hospitalization

Study Arms (3)

Tolvaptan 30 mg and IV Lasix

EXPERIMENTAL

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

Metolazone 5mg and IV Lasix

ACTIVE COMPARATOR

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

IV Lasix

ACTIVE COMPARATOR

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

Interventions

Tolvaptan 30 mg + IV Diuretics DRUG

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

Also known as: Tolvaptan (Samsca) and Lasix (Furosemide)

Tolvaptan 30 mg and IV Lasix

Metolazone 5 mg + IV Diuretics DRUG

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

Also known as: Metolazone (Zaroxolyn) and Lasix (Furosemide)

Metolazone 5mg and IV Lasix

2.5 times the Diuretics Dose DRUG

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

Also known as: Lasix (Furosemide)

IV Lasix

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Cardiomyopathies; Heart Failure

Interventions

Tolvaptan; Diuretics; Furosemide; Metolazone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Natriuretic Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines

Study Officials

• Divya Gupta, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 5, 2016
• Study Start: January 1, 2016
• Primary Completion: December 30, 2018
• Study Completion: December 30, 2018
• Last Updated: March 27, 2019

Record last verified: 2019-03

Locations

US (2)