AiDing Diuresis wIth Tolvaptan (ADD-IT)

NCT ID: NCT02646540

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-12-30

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).

Conditions

Cardiomyopathy; Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tolvaptan 30 mg + IV Diuretics

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Metolazone 5 mg + IV Diuretics

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

2.5 times the Diuretics Dose

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Tolvaptan (Samsca) and Lasix (Furosemide); Metolazone (Zaroxolyn) and Lasix (Furosemide); Lasix (Furosemide)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Divya Gupta

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Divya Gupta, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00080051

Identifier Type: -

Identifier Source: org_study_id