Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study

Study Overview
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Brief Summary
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To determine if a strategy of early discharge using a novel subcutaneous delivery system for parenteral furosemide can improve clinical outcomes within 30 days of randomization (days alive and outside the hospital) compared to usual care.

Detailed Description
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SUBQ-HF is a multicenter clinical trial of selected AHF patients with persistent congestion. This study will evaluate a strategy of early discharge (pathway 1) or admission avoidance (pathway 2) with daily SQ furosemide compared to usual care in a population who have objective evidence of persistent congestion requiring ongoing parenteral diuretics. This will be an unblinded, randomized, controlled study of approximately 300 evaluable patients. Eligible patients will be randomized (1:1) to either: Usual care strategy, during which patients will have continued inpatient treatment and discharge follow-up as per usual standard of care plus a Day 7 phone call and Day 30 study visit. or Subcutaneous strategy, in which patients will be discharged home within 24 hours of randomization (pathway 1) or sent home from clinic or ED to receive furosemide with the SQ pump for 1-7 days (based on clinical response) plus a Day 7 and Day 30 visit. Subcutaneous furosemide/early discharge strategy: Subjects will receive device training and study materials (SQ pump device and up to a 7 day supply of SQ furosemide vials) on the day of randomization (study day 0) and discharged within 24 hours. Training will include instruction on daily weights and dyspnea numerical rating for symptoms. Scales will be provided to subjects. Subjects will be discharged with planned treatment of 80 mg SQ furosemide injection over 5-hours either QD or BID, depending on anticipated diuretic requirements. If there are unanticipated delays in discharge after randomization, subjects will continue with their assigned therapy and assessments in the hospital. Discharged subjects will receive a phone contact from study team on D1, D3, and D5 in order to assess adequacy of diuresis, persistence of congestion, and planned duration, dose of ongoing SQ therapy (see Appendix for guidelines on adjusting therapy) and adverse events. Additional clinical contact (additional phone contacts or clinical visits) may be performed if felt clinically indicated by the study team or clinical provider. All subjects will have assessment of electrolytes and renal function by protocol 2 days post discharge. More frequent electrolyte monitoring can be performed at the discretion of the study team or clinical provider as clinically indicated. Patients receiving the SQ pump for outpatient use should be prescribed a supplementation regimen based on electrolyte supplementation needs in the hospital with IV diuretic therapy. The duration of subcutaneous therapy will be planned for 1-7 days depending on clinical response. Dose and frequency of oral diuretics once SQ therapy is completed will be per the discretion of the treating physician. Usual care strategy: Subjects randomized to usual care will continue to receive inpatient therapy, eventual transition to oral diuretics, and discharge and post discharge care as per the discretion of the treating clinician and standard treatment guidelines. In addition, they will have a Day 7 study phone call and a Day 30 study visit.

Official Title
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Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Study

Conditions
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Acute Heart Failure, Decompensated Heart Failure

Intervention / Treatment
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* Combination Product: subcutaneous furosemide and sc2wear device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Pathway 1 (patients hospitalized with acute heart failure) Age >18 years Willingness and ability to provide informed consent Hospitalization for AHF with at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography, BNP > 250 ng/mL or NTproBNP > 1000 ng/mL) of congestion Persistent congestion defined by the presence of at least 2 or more of the following at the time of consent: Peripheral edema Rales Elevated JVP Ascites BNP > 250 ng/mL or NTproBNP > 1000 ng/mL during index hospitalization Orthopnea Total anticipated daily IV furosemide dose (at time of screening) >80-240 mg (or equivalent)/day Anticipated need for at least 24 more hours of parenteral diuretic therapy Exclusion Criteria for Pathway 1 Severe renal dysfunction (eGFR< 20 ml/min/1.73m2) within 24 hours of enrollment Requirement for inotropes (other than digoxin) or mechanical support during hospitalization Clinically significant electrical instability during hospitalization Anticipated need for ongoing intravenous therapies beyond diuretics (electrolyte repletion, vasodilators, antibiotics, etc.) Planned discharge to location other than home (e.g., hospice, skilled nursing facility, etc.) Anticipated cardiac transplantation or left ventricular assist device within the next 30 days Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade Known or anticipated pregnancy in the next 30 days Prior use of a subcutaneous furosemide pump or current use of any subcutaneous pump, on-body infusion devices or patients who give regimented injections at the intended site of the furosemide infusion device. Other psychosocial or physical barriers to following the protocol and using SQ pump device outside the hospital setting Known allergy to furosemide Known sensitivity or allergy to medical adhesive tape Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months Presentation is for indication other than CHF Inclusion Criteria for Pathway 2 (Outpatients with heart failure presenting with volume overload necessitating treatment with parenteral loop diuretics) Age >18 years Willingness and ability to provide informed consent HF now presenting with volume overload defined by the presence of at least 2 or more of the following at the time of consent: Peripheral edema Rales Elevated JVP Ascites BNP > 250 ng/mL or NTproBNP > 1000 ng/mL during this episode of decompensation Orthopnea Need for parenteral furosemide with an estimated SQ furosemide requirement between 80-240 mg/day Anticipated need for at least 24 hours of parenteral diuretic therapy Exclusion Criteria for Pathway 2 Severe renal dysfunction (eGFR< 20 ml/min/1.73m2) within 24 hours of enrollment Anticipated need for inotropes (other than digoxin) or mechanical support to treat current episode of decompensation Clinically significant electrical instability requiring hospitalization Anticipated need for ongoing intravenous therapies beyond diuretics (electrolyte repletion, vasodilators, antibiotics, etc.) Residence at location other than home (e.g., hospice, skilled nursing facility, etc.) Anticipated cardiac transplantation or left ventricular assist device within the next 30 days Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade Known or anticipated pregnancy in the next 30 days Prior use of a subcutaneous furosemide pump or current use of any subcutaneous pump, on-body infusion devices or patients who give regimented injections at the intended site of the furosemide infusion device. Other psychosocial or physical barriers to following the protocol and using SQ pump device outside the hospital setting Known allergy to furosemide Known sensitivity or allergy to medical adhesive tape Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months. Presentation is for indication other than CHF.

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: Subcutaneous Furosemide and sc2wear device<br>Subjects will receive device training and study materials (SQ pump device and up to a 7 day supply of SQ furosemide vials) on the day of randomization (study day 0) and discharged within 24 hours. Subjects will be discharged with planned treatment of 80 mg subcutaneous furosemide injection over 5-hours either QD or BID, depending on anticipated diuretic requirements. | Combination Product: subcutaneous furosemide and sc2wear device<br>* subcutaneous furosemide administered via sc2wear device vs. standard of care<br>|
| No Intervention: Usual Care<br>Subjects randomized to usual care will continue to receive inpatient therapy, eventual transition to oral diuretics, and discharge and post discharge care as per the discretion of the treating clinician and standard treatment guidelines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Safety Measured by Serious Adverse Events | measured by serious adverse events | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Safety Endpoint of Death, Sustained Ventricular Arrhythmias, and Severe Hypokalemia |  | 30 days | 
| Medical Costs From Randomization Through 30 Days |  | 30 days | 
| Days Alive and Outside the Hospital Through 14 Days |  | 14 days | 
| 30 Day Heart Failure Readmission |  | 30 days | 
| 30 Day ED Visit for Heart Failure |  | 30 days | 
| Death at 30 Days |  | 30 days | 
| Change in Breathlessness Through Day 7 | On a 0-10 scale of breathlessness | 7 days | 
| Change in Renal Function Using eGFR Baseline to 30 Days |  | 30 days | 
| Change in NT Pro BNP From Baseline to 30 Days |  | 30 days |