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

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.

Study Overview

• Status: Terminated
• Conditions: Decompensated Heart Failure; Acute Heart Failure
• Intervention / Treatment: Combination product: subcutaneous furosemide and sc2wear device

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63117
      • Saint Louis University Hospital
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44109
      • Metro Health System
    • Cleveland, Ohio, United States, 44106
      • University Hospitals- Case Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvaina
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for Pathway 1 (patients hospitalized with acute heart failure)

1. Age >18 years
2. Willingness and ability to provide informed consent
3. 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

4. Persistent congestion defined by the presence of at least 2 or more of the following at the time of consent:

   1. Peripheral edema
   2. Rales
   3. Elevated JVP
   4. Ascites
   5. BNP > 250 ng/mL or NTproBNP > 1000 ng/mL during index hospitalization
   6. Orthopnea
5. Total anticipated daily IV furosemide dose (at time of screening) >80-240 mg (or equivalent)/day
6. Anticipated need for at least 24 more hours of parenteral diuretic therapy

Exclusion Criteria for Pathway 1

1. Severe renal dysfunction (eGFR< 20 ml/min/1.73m2) within 24 hours of enrollment
2. Requirement for inotropes (other than digoxin) or mechanical support during hospitalization
3. Clinically significant electrical instability during hospitalization
4. Anticipated need for ongoing intravenous therapies beyond diuretics (electrolyte repletion, vasodilators, antibiotics, etc.)
5. Planned discharge to location other than home (e.g., hospice, skilled nursing facility, etc.)
6. Anticipated cardiac transplantation or left ventricular assist device within the next 30 days
7. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
8. Known or anticipated pregnancy in the next 30 days
9. 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.
10. Other psychosocial or physical barriers to following the protocol and using SQ pump device outside the hospital setting
11. Known allergy to furosemide
12. Known sensitivity or allergy to medical adhesive tape
13. Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months
14. 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)

1. Age >18 years
2. Willingness and ability to provide informed consent

3. HF now presenting with volume overload defined by the presence of at least 2 or more of the following at the time of consent:

   1. Peripheral edema
   2. Rales
   3. Elevated JVP
   4. Ascites
   5. BNP > 250 ng/mL or NTproBNP > 1000 ng/mL during this episode of decompensation
   6. Orthopnea
4. Need for parenteral furosemide with an estimated SQ furosemide requirement between 80-240 mg/day
5. Anticipated need for at least 24 hours of parenteral diuretic therapy

Exclusion Criteria for Pathway 2

1. Severe renal dysfunction (eGFR< 20 ml/min/1.73m2) within 24 hours of enrollment
2. Anticipated need for inotropes (other than digoxin) or mechanical support to treat current episode of decompensation
3. Clinically significant electrical instability requiring hospitalization
4. Anticipated need for ongoing intravenous therapies beyond diuretics (electrolyte repletion, vasodilators, antibiotics, etc.)
5. Residence at location other than home (e.g., hospice, skilled nursing facility, etc.)
6. Anticipated cardiac transplantation or left ventricular assist device within the next 30 days
7. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade
8. Known or anticipated pregnancy in the next 30 days
9. 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.
10. Other psychosocial or physical barriers to following the protocol and using SQ pump device outside the hospital setting
11. Known allergy to furosemide
12. Known sensitivity or allergy to medical adhesive tape
13. Enrollment or planned enrollment in another therapeutic clinical trial in next 3 months.
14. Presentation is for indication other than CHF.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subcutaneous Furosemide and sc2wear device; 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; subcutaneous furosemide administered via sc2wear device vs. standard of care
No Intervention: Usual Care; 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?

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

Collaborators and Investigators

• Sponsor: Adrian Hernandez

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2018
• Primary Completion (Actual): September 20, 2018
• Study Completion (Actual): September 20, 2018

Study Registration Dates

• First Submitted: May 6, 2017
• First Submitted That Met QC Criteria: May 25, 2017
• First Posted (Actual): May 30, 2017

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 1, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• 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: Pro00070619

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: Yes