search
Back to results

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

Primary Purpose

Cardiomyopathy, Congestive Heart Failure

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tolvaptan 30 mg + IV Diuretics
Metolazone 5 mg + IV Diuretics
2.5 times the Diuretics Dose
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiomyopathy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Emory University Hospital Midtown
  • Emory University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Tolvaptan 30 mg and IV Lasix

Metolazone 5mg and IV Lasix

IV Lasix

Arm Description

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.

Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 5mg metolazone concomitantly with their standard dose of diuretics.

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.

Outcomes

Primary Outcome Measures

Length of Hospitalization Measured in Days
The number of days hospitalized until discharge.

Secondary Outcome Measures

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

Full Information

First Posted
January 4, 2016
Last Updated
March 25, 2019
Sponsor
Emory University
search

1. Study Identification

Unique Protocol Identification Number
NCT02646540
Brief Title
AiDing Diuresis wIth Tolvaptan (ADD-IT)
Acronym
ADD-IT
Official Title
AiDing Diuresis wIth Tolvaptan (ADD-IT)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
December 30, 2018 (Actual)
Study Completion Date
December 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiomyopathy, Congestive Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tolvaptan 30 mg and IV Lasix
Arm Type
Experimental
Arm Description
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.
Arm Title
Metolazone 5mg and IV Lasix
Arm Type
Active Comparator
Arm Description
Participants admitted to the hospital and diagnosed with acutely decompensated heart failure (ADHF) will receive 5mg metolazone concomitantly with their standard dose of diuretics.
Arm Title
IV Lasix
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tolvaptan 30 mg + IV Diuretics
Other Intervention Name(s)
Tolvaptan (Samsca) and Lasix (Furosemide)
Intervention Description
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
Intervention Name(s)
Metolazone 5 mg + IV Diuretics
Other Intervention Name(s)
Metolazone (Zaroxolyn) and Lasix (Furosemide)
Intervention Description
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
Intervention Name(s)
2.5 times the Diuretics Dose
Other Intervention Name(s)
Lasix (Furosemide)
Intervention Description
Participants will receive two and a half (2.5) times their standard dose of intravenous (IV) diuretics for the duration of their hospitalization.
Primary Outcome Measure Information:
Title
Length of Hospitalization Measured in Days
Description
The number of days hospitalized until discharge.
Time Frame
Duration of Hospitalization (Average of Five Days)
Secondary Outcome Measure Information:
Title
Change in Body Weight
Description
The difference in body weight from hospital admission to discharge measured in kilograms.
Time Frame
Baseline (hospital admission), Discharge (Average of 5 Days)
Title
Total Diuretic Dose
Description
The total dose of diuretics given throughout the duration of hospitalization measured in milligrams (mg).
Time Frame
Up to Five Days
Title
Change in estimated glomerular filtration rate (eGFR)
Description
The difference in eGFR from baseline (hospital admission) to discharge.
Time Frame
Baseline (hospital admission), Discharge (Average of 5 days)
Title
Number of Days Alive
Description
The number of days participants remain alive over thirty days after hospital discharge.
Time Frame
Post Hospital Discharge (30 days)
Title
Rate of Re-Hospitalization
Description
The number of participants re-hospitalized for worsening heart failure or death at 30 days.
Time Frame
30 Days Post Hospitalization
Title
Number of Electrolyte Imbalance Related Adverse Events
Description
The number of adverse events due to electrolyte imbalance throughout the duration of hospitalization.
Time Frame
Duration of Hospitalization (Average of Five Days)
Title
Number of Participants Requiring Electrolyte Repletion
Description
The number of participants that require electrolyte repletion throughout the duration of hospitalization.
Time Frame
Duration of Hospitalization (Average of Five Days)
Title
Change in Sodium Level
Description
The difference in sodium levels from baseline to hospital discharge measured in milliequivalents per liter (mEqL).
Time Frame
Baseline (hospital admission), Discharge (Average of 5 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Divya Gupta, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Learn more about this trial

AiDing Diuresis wIth Tolvaptan (ADD-IT)

We'll reach out to this number within 24 hrs