Acute Heart Failure
Conditions
Brief summary
The Pilot study is designed to evaluate the overall safety and feasibility of a strategy based on subcutaneous delivery of furosemide. It will be used to inform the subsequent evaluation phase of the study (separate protocol). The primary objective of the study is to determine if a strategy of a novel subcutaneous delivery of furosemide is safe and feasible in patients with acute heart failure.
Detailed description
Multi-center, open-label, pilot study conducted in 2 phases. Each phase will enroll 20 subjects that will be used to inform the study design of the SUBQ-HF Study (approximately 300 evaluable patients randomized to either usual inpatient care or early discharge with home subcutaneous furosemide for 1-7 days). Inpatient Pilot Phase: Eligible in-patients will be approached for participation. Subjects who consent for participation will be treated with subcutaneous furosemide for 48 hours, during which they will remain in the hospital. This will be primarily a safety and feasibility assessment. There will be no formal hypothesis tested, and statistical analysis will be descriptive in nature. Outpatient Pilot Phase: Eligible in-patients who are nearing discharge will be approached for participation. Subjects who consent for participation will be instructed on use of device, discharged to home and treated at home with subcutaneous furosemide for 1-7 days. This will be primarily a safety and feasibility assessment. There will be no formal hypothesis tested, and statistical analysis will be descriptive in nature.
Interventions
DRUGFurosemide
subcutaneous furosemide delivered via subcutaneous pump
Sponsors
Adrian Hernandez
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 years 2. Willingness and ability to provide informed consent 3. Hospitalization for acute heart failure (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, Brain Natriuretic Peptide \> 250 ng/mL or N-terminal pro-brain natriuretic peptide (NTproBNP) \> 1000 ng/mL) of congestion 4. Persistent congestion despite at least 18 hours of intravenous (IV) therapy, defined by the presence of at least 2 or more of the following at the time of consent: * Peripheral edema * Rales * Elevated jugular venous pressure (JVP) * Ascites * BNP \> 250 ng/mL or NTproBNP \> 1000 ng/mL 5. Total anticipated daily IV furosemide dose (at time of screening) \>80-200 mg (or equivalent)/day 6. Anticipated need for at least 24 more hours of parenteral diuretic therapy -
Exclusion criteria
1. Severe renal dysfunction (Estimated Glomerular Filtration Rate (eGFR)\< 30 ml/min/1.73m2) 2. Requirement for inotropes (other than digoxin) or mechanical support during hospitalization 3. Clinically significant electrical instability during hospitalization 4. Ongoing need for other intravenous therapies beyond diuretics (vasodilators, antibiotics, etc.) 5. Anticipated need for ongoing parenteral electrolyte repletion 6. Planned discharge to location other than home (e.g, hospice, skilled nursing facility, etc.) 7. Anticipated cardiac transplantation or left ventricular assist device within the next 30 days 8. Primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy, acute myocarditis, constrictive pericarditis or tamponade 9. Known or anticipated pregnancy in the next 30 days Prior use of 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 a subcutaneous pump device outside the hospital setting 11. Unable to accurately measure urine output 12. Known allergy to furosemide 13. Known sensitivity or allergy to medical adhesive tape
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events | 14 days | The analysis of data from the Pilot Phase will be primarily descriptive in nature and there will be no formal hypothesis testing. Number of patients with events will be reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| In-patient Pilot Study All subjects in the in-patient pilot study will receive the subcutaneous pump to administer a special formulation of furosemide to be delivered subcutaneously.
Furosemide: subcutaneous furosemide delivered via subcutaneous pump | 20 |
| Out-patient Pilot Study All subjects in the out-patient study will receive the subcutaneous pump to administer a special formulation of furosemide to be delivered subcutaneously.
Furosemide: subcutaneous furosemide delivered via subcutaneous pump | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | In-patient Pilot Study | Total | Out-patient Pilot Study |
|---|---|---|---|
| Age, Continuous | 68.2 years STANDARD_DEVIATION 14.6 | 63.0 years STANDARD_DEVIATION 14.2 | 57.8 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 39 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 30 Participants | 16 Participants |
| Region of Enrollment United States | 20 participants | 40 participants | 20 participants |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Male | 12 Participants | 28 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 4 / 20 | 8 / 20 |
| serious Total, serious adverse events | 0 / 20 | 1 / 20 |
Outcome results
Primary
Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events
The analysis of data from the Pilot Phase will be primarily descriptive in nature and there will be no formal hypothesis testing. Number of patients with events will be reported.
Time frame: 14 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| In-patient Pilot | Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events | Patients with any Adverse Events | 4 participants |
| In-patient Pilot | Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events | Patients with no Events | 16 participants |
| Out-patient Pilot Study | Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events | Patients with any Adverse Events | 9 participants |
| Out-patient Pilot Study | Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events | Patients with no Events | 11 participants |
Comparison: All subjects on study received active drug.