AiDing Diuresis wIth Tolvaptan (ADD-IT)

Congestive Heart Failure Clinical Trial

— ADD-IT  

Official title:

AiDing Diuresis wIth Tolvaptan (ADD-IT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02646540
• Other study ID #: IRB00080051
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: December 30, 2018

Study information

• Verified date: March 2019
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: December 30, 2018
• Est. primary completion date: December 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy
• Congestive Heart Failure
• Heart Failure

Intervention

Drug:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Length of Hospitalization Measured in Days	The number of days hospitalized until discharge.	Duration of Hospitalization (Average of Five Days)
Secondary	Change in Body Weight	The difference in body weight from hospital admission to discharge measured in kilograms.	Baseline (hospital admission), Discharge (Average of 5 Days)
Secondary	Total Diuretic Dose	The total dose of diuretics given throughout the duration of hospitalization measured in milligrams (mg).	Up to Five Days
Secondary	Change in estimated glomerular filtration rate (eGFR)	The difference in eGFR from baseline (hospital admission) to discharge.	Baseline (hospital admission), Discharge (Average of 5 days)
Secondary	Number of Days Alive	The number of days participants remain alive over thirty days after hospital discharge.	Post Hospital Discharge (30 days)
Secondary	Rate of Re-Hospitalization	The number of participants re-hospitalized for worsening heart failure or death at 30 days.	30 Days Post Hospitalization
Secondary	Number of Electrolyte Imbalance Related Adverse Events	The number of adverse events due to electrolyte imbalance throughout the duration of hospitalization.	Duration of Hospitalization (Average of Five Days)
Secondary	Number of Participants Requiring Electrolyte Repletion	The number of participants that require electrolyte repletion throughout the duration of hospitalization.	Duration of Hospitalization (Average of Five Days)
Secondary	Change in Sodium Level	The difference in sodium levels from baseline to hospital discharge measured in milliequivalents per liter (mEqL).	Baseline (hospital admission), Discharge (Average of 5 days)