Furoscix Real-World Evaluation for Decreasing Hospital Admissions in Heart Failure

Study Overview
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Brief Summary
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The study is to evaluate the safe admission avoidance and the overall economic impact associated with management of worsening HF using the drug-device combination product, the Furoscix Infusor, outside the hospital setting in patients initially presenting to the emergency department. The study drug, Furoscix (furosemide injection 8 mg/ml), is a furosemide solution buffered to a neutral pH containing 80 mg/10 mL for subcutaneous administration over 5 hours via the Furoscix Infusor. The study objectives are: To evaluate differences in healthcare resource utilization and direct medical costs for patients treated with the Furoscix Infusor outside the hospital versus patients receiving intravenous furosemide for ≤ 72 hours in the hospital setting for 30 days post-discharge from the emergency department. To evaluate the safety of Furoscix administered outside the hospital. To evaluate and describe quality of life and patient satisfaction for patients who receive the Furoscix Infusor outside the hospital setting.

Detailed Description
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This adaptive clinical trial will include a prospective treatment arm (i.e., Furoscix administered via the Furoscix Infusor) administered outside the hospital that will be compared to a propensity-matched historical control arm of patients admitted to the hospital for ≤ 72 hours (i.e., Treatment As Usual (TAU)) that will be derived from administrative claims data. Eligible patients for the Furoscix arm will be patients with HF and fluid overload who initially present to the emergency department (ED) and who are expected to require parenteral diuresis. If it is determined by the investigator that the patient requires parenteral diuresis or continued diuresis outside of the ED care setting and meets all study eligibility criteria, he/she may be consented and enrolled into the study. The treatment comprises a preprogrammed bi-phasic 5-hour drug administration. Subjects will be instructed on the use of the Furoscix Infusor by the investigator and/or study staff in accordance with the instructions for use. The initial dose of the study product may be administered in the ED or at home. Additional doses will be provided to the subject for self-administration or administration by a caregiver in the home setting as directed by the investigator or study staff. The total duration in days and total number of doses of the initial therapy will be determined by the investigator based on an estimated volume of diuresis desired to transition patient back to their oral diuretic maintenance therapy. Subjects will receive scheduled at-home telephone calls from a HF nurse on Days 1 and 7 and one call between Days 14-21. Planned in-clinic visits will be conducted between Day 2-4 and then Day 30. Unscheduled at-home telephone calls by a HF nurse and unscheduled in-clinic visits may be performed if felt clinically indicated by the study team or the clinical provider. The study period will be up to 30 days after enrollment. All outcomes will be assessed up to 30 days after the initial discharge from the emergency department.

Official Title
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Economic Impact of Reducing Hospital Admissions for Patients Presenting to the Emergency Department With Worsening Heart Failure: An Adaptive Clinical Trial of Furoscix Infusor

Conditions
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Heart Failure

Intervention / Treatment
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* Combination Product: Furoscix Infusor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years NYHA Class II-III HF presenting to the emergency department for worsening HF at baseline On background therapy includes those receiving 40-160 mg of oral furosemide equivalents daily (20-80 mg Torsemide or 1-4 mg Bumetanide). Signs of extracellular volume expansion, defined as one or more of the following: jugular venous distention pitting edema (≥1+), abdominal distension pulmonary congestion on chest x-ray pulmonary rales After initial emergency department evaluation and treatment (i.e., at the time of the care transition decision*), candidates for parenteral diuresis outside of the hospital, defined as all the following: Oxygen saturation ≥ 90% on exertion Respiratory Rate < 24 breaths per minute Resting Heart Rate < 100 beats per minute Systolic Blood Pressure > 100 mmHg Adequate environment for at-home administration of Furoscix Exclusion Criteria: Presence of a complicating condition, other than HF that requires immediate hospitalization or anticipated hospitalization in the next 30 days Evidence of acute renal failure as determined at the discretion of the investigator Known allergy to the active and inactive ingredients of the study medication or device adhesive Any local abdominal skin condition on the day of treatment i.e. sunburn, rash, eczema, etc. Currently participating in another interventional research study Women who are pregnant or who could become pregnant and are not willing to use an adequate form of contraception Estimated Creatinine Clearance < 30 mL per minute by Cockcroft-Gault equation CrCl (mL/min) = {(140 - age) x Lean Body Weight (kg)/Serum Creatinine (mg/dL) x 72} (x 0.85 if female) If baseline creatinine value is available: an increase of ≥ 0.5 mg/dL in creatinine from baseline HF requiring immediate hospitalization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A prospective treatment arm (i.e., Furoscix administered via the Furoscix Infusor) administered outside the hospital that will be compared to a propensity-matched historical control arm of patients admitted to the hospital for ≤ 72 hours (i.e., Treatment As Usual (TAU)) that will be derived from administrative claims data.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furoscix Infusor Prospective Treatment<br>Furoscix (furosemide injection, 8 mg/mL) administered subcutaneously over 5 hours via the Furoscix Infusor outside the hospital. | Combination Product: Furoscix Infusor<br>* Furoscix Infusor, a drug-device combination product for subcutaneous delivery of Furoscix, buffered furosemide injection, 8 mg/mL (total dose = 80 mg dose) administered subcutaneously for 5 hours.<br>|
| No Intervention: Propensity-Matched Historical Control<br>The control arm will be populated with claims data for patients with HF and fluid overload who presented to the emergency department and were admitted to the hospital for ≤ 72 hours for the treatment of HF with intravenous diuretics. Patients admitted for diuresis-only will be identified by using diagnostic codes for admittance from a claims database. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthcare Utilization Costs | The difference in the overall and heart failure related healthcare costs between subjects treated with the Furoscix Infusor through 30 days post discharge from the emergency department compared to matched controls treated in the hospital for ≤ 72 hours through 30 days post discharge. | Day 0 - Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart-Failure Related Hospital Admissions | The HF-related admissions for the Furoscix patients compared to Control patients. | Day 0 - Day 30 | 
| All-Cause Hospital Admissions | The differences in the percentage of subjects with an all-cause hospitalization in the Furoscix group and all-cause 30-day rehospitalization in the Control group in the 30 day follow-up period | Day 0 - Day 30 | 
| Heart-Failure Related Emergency Department Visits | The differences in the percentage of patients with HF-related emergency department visits in the Furoscix group and in the Control group in the 30 day follow-up period | Day 0 - Day 30 | 
| Heart-Failure Related Clinic Visits | The differences in the percentage of patients with HF-related clinic visits in the Furoscix group and in the Control group in the 30 day follow-up period | Day 0 - Day 30 | 
| KCCQ-12 Scores | The Kansas City Cardiomyopathy Questionnaire (KCCQ) measures a patient's self-reported overall health status, which includes heart failure symptoms, impact on physical and social function, and how their heart failure impacts their quality of life (QOL). The KCCQ-12 overall summary score is the sum of responses from all 12 items ranging from 0 to 100 with higher scores to indicate better health status. | 30 Days | 
| Mean Change in NT-proBNP and BNP | Change in NT-proBNP and BNP change from baseline during the study period is summarized for the Furoscix group | Day 0 - Day 30 | 
| Comfort of Wear Questionnaire | The Furoscix group was administered a Comfort of Wear Questionnaire during Day 2-4 study visit. This questionnaire measured the patient's general perception of comfortability wearing and using the device, the impact of wearing the device on their activities of daily living, and their satisfaction with the device. | Day 0 - Day 2-4 study visit | 
| Comfort of Wear Questionnaire: Interference With Activities Daily Living | The Furoscix group was administered a Comfort of Wear Questionnaire on Day 2-4. This questionnaire measured the patient's general perception of comfortability wearing and using the device, the impact of wearing the device on their activities of daily living, and their satisfaction with the device. | Day 0 - Day 2-4 study visit | 
| Comfort of Wear Questionnaire: Subject and/or Caregiver Satisfaction | The Furoscix group was administered a Comfort of Wear Questionnaire during Day 2-4 study visit. This questionnaire measured the patient's general perception of comfortability wearing and using the device, the impact of wearing the device on their activities of daily living, and their satisfaction with the device. | Day 0 - Day 2-4 study visit |