Avoiding Treatment in the Hospital With Furoscix for the Management of Congestion in Heart Failure - A Pilot Study

Study Overview
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Brief Summary
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This is a multicenter, randomized, open label, controlled study evaluating the effectiveness, and safety of the Furoscix Infusor vs continued medical therapy in patients with chronic heart failure and fluid overload requiring augmentation in diuretic therapy outside of acute care setting. 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 provide pilot data on the effectiveness and safety to inform a pivotal trial. To inform population enrichment strategies To refine pivotal trial endpoints and analytical methods To identify operational challenges of study design To assess patient adherence, competence, and experience To familiarize staff and patients with device application and use

Detailed Description
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The purpose of this study is to evaluate the effectiveness and safety of the Furoscix Infusor vs continued medical therapy in patients with chronic heart failure and fluid overload requiring augmentation in diuretic therapy outside of acute care setting. 51 patients will be randomly assigned (2:1) to receive Furoscix vs continued medical therapy. The Treatment Phase comprises a pre-programmed bi-phasic 5-hour drug administration of Furoscix (80 mg/10 mL) via the On-body Infusor. Subjects and/or their caregivers will be trained on device preparation, placement and removal in accordance with product instructions of use (IFU). Subjects should be transitioned back to their oral maintenance diuretic regimen when clinically indicated at the discretion of the investigator. Over the initial 7 days, all subjects will receive daily clinic or phone follow-up by the study staff. Decision of treatment with Furoscix in the intervention arm as well as changes in oral diuretic dosing in the control arm will be determined by the treating physician in coordination with the study nurse. Safety labs will be done on Days 1, 3, 7 and 30. After Subjects have been transitioned to their oral maintenance diuretic regimen, additional doses of Furoscix (for Furoscix group) or IV diuretics (for Treat as Usual group) can be prescribed during the 30-day study period as needed based on the presence of congestion symptoms (e.g. dyspnea, edema, and/or excess weight gain) as determined by the investigator. The Follow-Up Phase will include a visit to the clinic on Day 30 +/- 5 days where effectiveness and safety assessments will be performed including limited physical exam (including NYHA Class), Composite Congestion Score (CCS), 5-point Current Dyspnea Score, 7-point Dyspnea Score, vital signs, laboratory analyses, KCCQ-12, Visual Analog Score (VAS), 6MWT and adverse events.

Official Title
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A Multicenter, Randomized, Open Label, Controlled Study Evaluating the Effectiveness and Safety of Furoscix On-Body Infusor vs Continued Medical Therapy for Worsening Heart Failure

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: Subjects are eligible for inclusion only if all the following criteria are met: Age 18 years or older. Diagnosis of symptomatic chronic heart failure (NYHA Class II-IV) with background loop diuretic therapy for at least 4 weeks. Need for augmented diuresis outside of the acute care setting as determined by the investigator. On background therapy including daily total furosemide equivalent dose (40-160 mg) of loop diuretic or equivalent. The subject must have signs of volume expansion, defined as two or more of the following six signs: jugular venous distention edema (≥ 1+) ascites pulmonary congestion on chest x-ray pulmonary rales NT-proBNP ≥1000 pg/ml (1400 for patients in atrial fibrillation) or, for patients not on Entresto, BNP ≥200 (400 for patients in atrial fibrillation) Increase over the preceding 30 days in at least one of the following symptoms characteristic of worsening heart failure: dyspnea fatigue exercise intolerance Adequate environment for at home administration of Furoscix by patient or caregiver. Exclusion Criteria: A Subject is not eligible for inclusion if any of the following criteria apply: Suspected high risk clinical instability with outpatient treatment. Presence of a complicating condition, other than heart failure likely to require hospitalization in next 30 days. Pregnant women or women of childbearing age who are not willing to use an adequate form of contraception. Known allergy to the active and inactive ingredients of the study medication or device adhesive. On experimental medication or currently participating in another interventional research study. eGFR < 20 Serum potassium at baseline > 5.4 or < 3.6 Concomitant infection Heart rate > 110 Received IV furosemide or bumetanide within last 24 hours

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Furoscix Infusor<br>Furoscix (furosemide injection, 8 mg/mL) administered subcutaneously over 5 hours via the Furoscix Infusor. The Infusor is applied to the abdomen via a medical grade adhesive and delivers a subcutaneous infusion of Furoscix through a pre-programmed, biphasic delivery profile with 30 mg (3.75 mL) administered over the first hour, followed by 12.5 mg (1.56 mL) per hour for the subsequent 4 hours (Total dose is 80 mg (10 mL) over 5 hours). | 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: Continued Medical Therapy<br>The subjects enrolled in this arm will receive treatment as usual | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Win Ratio of Composite Endpoint | Win Ratio calculated as number of pairs of Furoscix On-Body Infusor subject wins divided by number of pairs of Furoscix On-Body Infusor subject losses when compared to Continued Medical Therapy subjects. Components of Endpoint composite outcome: CV death, HF hospitalization, Urgent ED/Clinic visit at 30 days and percent change in NT-proBNP from baseline at Day 7. See Statistical Analysis Plan for detailed explanation of this statistical method. | Day 7, Day 30 | 
| Number of Cardiovascular Deaths | Total number of CV deaths between two groups | Baseline, 30 Days | 
| Number of Heart Failure Hospitalizations | Heart Failure hospitalizations compared between two groups | 30 Days | 
| Number of Urgent ED/Clinic Visits for Worsening Heart Failure | Urgent ED/Clinic visits for worsening heart failure compared between two groups. Statistical analysis was not performed due to no ED/Clinic visits | 30 Days | 
| NT-proBNP Change From Baseline | Percentage change in NT-proBNP from baseline at Day 7 compared between two groups | 30 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Heart Failure Event Free Survival Days | Out of 30 days, HF event-free survival is the average number of days subjects survived outside the hospital event-free. | 30 Days | 
| Number of Subjects Deceased or HF Event Occurred | Subjects that are Deceased or HF event occurred (hospitalization for HF or urgent ED/clinic visits for HF) over 30 days compared between treatment groups. | 30 Days | 
| Visual Analog Scale (VAS) | The patient global assessment VAS is a patient-reported assessment of how good or bad a patient feels their health is on a given day. It is reported on a visual scale of 0 to 100, with 0 being the worst health they can imagine and 100 being the best health they can imagine. | Baseline, 7 Days, 30 Days | 
| Composite Congestion Score (CCS) | The composite congestion score (ccs) is calculated by summing the individual scores for orthopnea, pedal edema and jugular venous distension. The investigator-assessed the signs and symptoms of congestion (orthopnea, pedal edema, and jugular venous distension) on a 4-point grading scale ranging from 0 to 3. Higher score indicates greater severity of symptoms ranging from 0 to 9. | Baseline, Day 7, Day 30 | 
| 5-Point Current Dyspnea Score | The 5-Point Current Dyspnea Status Questionnaire is a single-item, self-administered instrument that quantifies current symptoms of dyspnea. The scale includes the absence of dyspnea (a score of 1), mild shortness of breath (a score of 2), moderate shortness of breath (a score of 3), severe shortness of breath (a score of 4) and the worst possible shortness of breath (a score of 5) | Baseline, Day 7, Day 30 | 
| 7-Point Dyspnea Score | The 7-Point Dyspnea Status Questionnaire is a single-item, self-administered instrument that quantifies changes in dyspnea symptoms since initiation of study product. The scale ranges from Markedly better, Moderately better, Minimaly better, No change, Minimally worse, Moderately worse to Markedly worse. | Baseline, Day 3, Day 7, Day 30 | 
| KCCQ-12 Summary Score | The KCCQ-12 questionnaire is a patient-reported assessment to capture symptom frequency, physical and social limitations, and quality-of-life impairment as a result of HF, as well as an overall summary score. In the KCCQ-12, responses are given for each individual item is scored on a scale of 0-100 with higher scores indicating better health. | Baseline, 7 Days, 30 Days | 
| Six-Minute Walk Test (6MWT) | Change from baseline in Six-Minute Walk Test (6MWT) across follow-up timepoints | Baseline, 7 Days, 30 Days | 
| Percent Lung Fluid | Lung fluid volume as measured via Remote Dielectric Sensing (ReDS) | Baseline, Day 7, Day 30 | 
| Body Weight | Body weight of the patient on the day of visit | Baseline, Day 3, Day 7, Day 30 | 
| Renal Function | Change from baseline in serum creatinine | Baseline, Day 3, Day 7, Day 30 |