OUTpatient Intravenous LASix Trial in Reducing Hospitalization for Acute Decompensated Heart Failure (OUTLAST)

OUTpatient Intravenous LASix Trial in Reducing Hospitalization for ADHF (OUTLAST)

Single-center, prospective double-blinded randomized control trial to evaluate the the feasibility, efficacy and safety of outpatient IV diuretic therapy in treatment of heart failure.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: IV Solution; Drug: Furosemide

Detailed Description

Patients were randomized by a clinical pharmacist with the ratio of 1:1:1 into 3 groups: standard of care control arm (Group 1), IV placebo infusion (Group 2), and IV furosemide infusion (Group 3).Patients in Group 2 and 3 received a comprehensive Heart Failure (HF)-care protocol that included bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Patients, nurses and treating physicians were blinded to the randomization. Patients in Group 1 received standard of care treatment per heart failure guidelines at the discretion of the primary cardiologist involved in the patient's care.8 Patients in Group 2 received IV saline infusion (20-40 ml) concentrated by the pharmacist to minimize fluid intake. Patients in Group 3 received IV furosemide calculated by the pharmacist to be equivalent or higher in dose compared to the patient's home oral dose. The dose assignments were categorized into low dose (20 mg bolus with 20 mg/hour infusion sessions and 2 ml saline), intermediate dose (40 mg bolus with 40 mg/hour infusion sessions and 4 ml saline) and high dose (80 mg bolus with 80 mg/hour infusion sessions). The infusions were continuous over 3 hours, biweekly over a one-month period. Infusions were held at the discretion of the physician utilizing a written protocol (creatinine 25% above baseline, Systolic Blood Pressure(SBP) <80 mmHg or symptoms of presyncope). Patients in both Groups 2 and 3 resumed all of their oral home medications for HF post infusion visits per standard of care.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients being admitted with ADHF over 18 years old
• Known history of systolic or diastolic dysfunction of greater than 6 weeks
• NYHA Class II-IV
• Heart failure as defined in [Table 1]. One symptom must be present at time of screening and one sign must be present in the last 12 months
• Elevated pro-BNP >/= 360 pg/ml and not explained by any other etiology
• Willing to consent and comply with scheduled visits and phone calls

Table 1. Criteria for Diagnosing Heart Failure

SYMPTOMS (at least 1 must be present at time of screening):

• Paroxysmal nocturnal dyspnea
• Orthopnea
• Dyspnea on mild or moderate exertion

SIGNS (at least 1 must be present in the last 12 months)

• Any rales post cough
• Jugular venous pressure >/= 10 cm H20
• Lower extremity edema
• Chest X-Ray (CXR) demonstrating pleural effusion, pulmonary congestion, or cardiomegaly

Exclusion Criteria:

• Systolic blood pressure <85 mmHg
• Signs of significant respiratory distress, according to the discretion of the investigator.
• Biventricular Implantable Cardioverter-Defibrillator(ICD) placement within 15 days, cardiogenic shock or volume depletion
• Chronic dialysis
• Acute renal failure defined as creatinine > 2 x baseline
• Severe systemic illness with life expectancy judged less than three years
• Chronic pulmonary disease requiring home O2, oral steroid therapy or hospitalization for exacerbation within 12 months, or significant chronic pulmonary disease in the opinion of the investigator
• Primary hemodynamically significant uncorrected valvular heart disease, obstructive, or regurgitant, or any valvular disease expected to lead to surgery during the trial.
• Atrial fibrillation with resting heart rate >90 bpm
• Myocardial infarction in past 90 days
• Percutaneous coronary intervention in past 30 days
• Heart transplant recipient or currently implanted left ventricular assist device
• Stroke in past 90 days
• No acute infection especially requiring IV antibiotics
• Allergy to Lasix
• Known chronic hepatic disease, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 3.0 times the upper limit of normal
• Non-verbal patients, patients who cannot speak or understand English, patients with dementia and psychiatric illness, patients who are blind or deaf and patients who are transferred to different hospital will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care (Group 1); Patients in Group 1 received standard of care treatment per heart failure guidelines at the discretion of the primary cardiologist involved in the patient's care.
Placebo Comparator: IV Placebo Infusion; Patients in Group 2 received IV saline infusion (20-40 ml) concentrated by the pharmacist to minimize fluid intake.The infusions were continuous over 3 hours, biweekly over a one-month period.	Drug: IV Solution; IV Placebo comparator; Other Names: IV Normal Saline 0.9%
Experimental: IV Furosemide Infusion; The dose assignments were categorized into low dose (20 mg bolus with 20 mg/hour infusion sessions and 2 ml saline), intermediate dose (40 mg bolus with 40 mg/hour infusion sessions and 4 ml saline) and high dose (80 mg bolus with 80 mg/hour infusion sessions). The infusions were continuous over 3 hours, biweekly over a one-month period.Infusions were held at the discretion of the physician utilizing a written protocol (creatinine 25% above baseline, SBP <80 mmHg or symptoms of presyncope).	Drug: Furosemide; IV loop diuretic therapy; Other Names: IV Furosemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Re-hospitalization for Heart Failure	30-day rehospitalization for Heart Failure	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kansas City Cardiomyopathy Questionnaire(KCCQ) outcome measures	Change in Quality of life will be quantified using KCCQ questionnaires	Change from Baseline to 30 days
Death, Myocardial Infarction, Stroke	Occurrence of death, myocardial infarction, or stroke	30 days, 180 days
PHQ-2 outcome measures	Change in depressive symptoms will be quantified using PHQ-2 questionnaire	Change from Baseline to 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
New York Heart Association (NYHA) Class	Change in NYHA functional class	Baseline and 30 days
LV function	Echo will be performed to evaluate heart function	Baseline and 30 days

Collaborators and Investigators

• Sponsor: New York Presbyterian Brooklyn Methodist Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2012
• Primary Completion (Actual): December 22, 2017
• Study Completion (Actual): December 22, 2017

Study Registration Dates

• First Submitted: December 23, 2020
• First Submitted That Met QC Criteria: December 29, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): December 31, 2020
• Last Update Submitted That Met QC Criteria: December 29, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: heart failure; mortality; hospitalization; diuretics; IV diuretics
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: 307139 (Other Identifier: New York-Presbyterian Brooklyn Methodist Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes