Clinical trial NCT02646540: AiDing Diuresis wIth Tolvaptan (ADD-IT)
Official title: AiDing Diuresis wIth Tolvaptan (ADD-IT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiomyopathy
Congestive Heart Failure
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2016-01-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Length of Hospitalization Measured in Days
timeFrame: Duration of Hospitalization (Average of Five Days)
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Baseline (hospital admission), Discharge (Average of 5 Days)
measure: Total Diuretic Dose
timeFrame: Up to Five Days
measure: Change in estimated glomerular filtration rate (eGFR)
timeFrame: Baseline (hospital admission), Discharge (Average of 5 days)
measure: Number of Days Alive
timeFrame: Post Hospital Discharge (30 days)
measure: Rate of Re-Hospitalization
timeFrame: 30 Days Post Hospitalization
measure: Number of Electrolyte Imbalance Related Adverse Events
timeFrame: Duration of Hospitalization (Average of Five Days)
measure: Number of Participants Requiring Electrolyte Repletion
timeFrame: Duration of Hospitalization (Average of Five Days)
measure: Change in Sodium Level
timeFrame: Baseline (hospital admission), Discharge (Average of 5 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Divya Gupta, MD
role: PRINCIPAL_INVESTIGATOR
References: