Furoscix in Heart Failure Patients With Diuretic Resistance

Study Overview
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Brief Summary
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This will be a randomized, open-label pilot study of 60 patients with and without diuretic resistance who were recently admitted and discharged for acute decompensated heart failure with and oral diuretic regimen testing whether Furoscix is more effective at achieving post-discharge outpatient diuresis than standard of care. Diuretic resistance will be identified using the BAN-ADHF (BUN, creAtinine, NP-levels, Age, Diabetes and DBP, HF hospitalization, and atrial Fibrillation) score which has been integrated into the electronic health record. The score is integer-based with a score of > 11 indicating diuretic resistance with high likelihood of poor outcomes. The primary outcome is diuretic efficacy as measured by volume of urine produced 8 hours after treatment and urine sodium levels (assessed hourly or per urination episode within 8 hours of treatment).

Detailed Description
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Heart failure is one of the leading causes of hospitalization in the United States, contributing to over 1 million emergency department visits and nearly 1 million hospitalizations for HF annually. The estimated mean cost for HF was $11,552 in 2014, totaling an estimated $11 billion. Thus, strategies to reduce the burden of acute care use for patients with heart failure are necessary. Acute decompensation of heart failure is characterized by volume overload and is primarily treated with intravenous diuretics. However, inefficient and ineffective diuresis both during hospitalization and in the post-discharge environment predispose patients to frequent readmission and a worse prognosis. Importantly, there is heterogeneity in patient response to intravenous diuresis, with an estimated 20-50% of patients having poor response to initial IV diuretic therapy. Patients who are resistant to intravenous diuresis have increased risk of rehospitalization and mortality. Importantly, our group recently derived an integer-based risk score (BAN-ADHF score) to predict patients with low diuretic efficiency. The investigators will screen eligible patients in the inpatient setting and schedule a research appointment within 14 days after discharge. At the research appointment, patients will be consented and undergo stratified randomization based on BAN-ADHF score (>11 vs. <=11). Within each stratum, patients will be randomized in a 1:1 ratio (intervention: control). The intervention arm (Furoscix over 5 hours at 8mg/mL) will be compared to a usual care group (home oral diuretic dose prescribed by discharge physician). Patients will be monitored for 8 hours in the Clinical Research Unit post-drug administration for clinical safety and to measure clinical response. This study will take place at the Clinical Research Unit in the Aston Building at UT Southwestern Medical Center.

Official Title
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Efficacy of Furoscix in Heart Failure Patients With Diuretic Resistance

Conditions
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Heart Failure

Intervention / Treatment
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* Combination Product: Furoscix
* Drug: Diuretic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: English speaking patients discharged after ward hospitalization for acute decompensated heart failure with admission NT-proBNP >1000 Able to be screened and enrolled within 14 days of hospitalization Recent echocardiogram (6 months or less) Discharged with home diuretic regimen Exclusion Criteria: Chronic kidney disease stage 5 (GFR<15) or End Stage Kidney Disease Systolic blood pressure <100 ICU hospitalization within 3 months Inotrope use within last 3 months Home inotropes Electrolyte abnormalities on discharge Inadequate data for BAN-ADHF score Pregnant Prior heart transplantation or left ventricular assist device Low-output heart failure Concurrent use of non-loop diuretic Advanced liver disease Severe malnutrition Skin/Soft tissue condition precluding Furoscix Inability to collect urine

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: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Patients will undergo stratified randomization based on BAN-ADHF score (>11 vs. <=11). Within each stratum, patients will be randomized in a 1:1 ratio (intervention: control).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: > 11 BAN-ADHF, Furoscix<br>Patients with diuretic resistance as determined by a BAN-ADHF score > 11 will receive Furoscix over 5 hours at 8 mg/mL. | Combination Product: Furoscix<br>* Study Drug: Furoscix®, (Furosemide Injection), 80 mg/10 mL is a proprietary furosemide formulation that is buffered to a neutral pH to enable subcutaneous administration and contained in a prefilled Crystal Zenith® (CZ) cartridge. Study Device: The Infusor is a compact, ethylene oxide (EtO) sterilized, single-use, electro-mechanical (battery powered, micro-processor controlled), on-body subcutaneous delivery system based on the SmartDose® Gen II 10 mL (West Pharmaceutical Services). The Furoscix Infusor is an investigational drug-device combination product. 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).<br>* Other names: subcutaneous furosemide;|
| Experimental: <= 11 BAN-ADHF, Furoscix<br>Patients without diuretic resistance as determined by BAN-ADHF score <= 11 will receive Furoscix over 5 hours at 8 mg/mL. | Combination Product: Furoscix<br>* Study Drug: Furoscix®, (Furosemide Injection), 80 mg/10 mL is a proprietary furosemide formulation that is buffered to a neutral pH to enable subcutaneous administration and contained in a prefilled Crystal Zenith® (CZ) cartridge. Study Device: The Infusor is a compact, ethylene oxide (EtO) sterilized, single-use, electro-mechanical (battery powered, micro-processor controlled), on-body subcutaneous delivery system based on the SmartDose® Gen II 10 mL (West Pharmaceutical Services). The Furoscix Infusor is an investigational drug-device combination product. 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).<br>* Other names: subcutaneous furosemide;|
| Active Comparator: > 11 BAN-ADHF, control<br>Patients with diuretic resistance as determined by a BAN-ADHF score > 11 will receive home dose oral diuretic. | Drug: Diuretic Therapy<br>* Patients will receive home dose oral furosemide or oral furosemide per standard of care.<br>|
| Active Comparator: <= 11 BAN-ADHF, control<br>Patients without diuretic resistance as determined by BAN-ADHF score <= 11 will receive home dose oral diuretic | Drug: Diuretic Therapy<br>* Patients will receive home dose oral furosemide or oral furosemide per standard of care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment diuretic efficiency as measured by cumulative urine output within 1 day. | Post-treatment diuretic efficiency is measured by cumulative urine output in mL per 40 mg of IV furosemide equivalent, observed at 1 hour, 4 hours, and 8 hours following the administration of study therapy (Furoscix vs. oral furosemide). | 1 day | 
| Post-treatment diuretic efficiency as measured by spot urine sodium levels in 1 day | Post-treatment diuretic efficiency is measured by spot urine sodium levels per 40 mg of IV furosemide equivalent assessed hourly over 8 hours post-treatment. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with post-intervention need for emergency department visit or hospitalization | The count of participants with post-intervention need for emergency department visit or hospitalization for worsening heart failure is assessed. | 7 days |