Congestive Heart Failure
Conditions
Keywords
Congestive heart failure, Furosemide
Brief summary
This study evaluates the clinical efficacy of subcutaneously administered Furosemide Injection Solution versus intravenous administration of Furosemide Injection, United States Pharmacopeia (USP) in adult patients presenting to a heart failure clinic with decompensated heart failure. Half of the patients will receive a subcutaneously administered Furosemide Injection Solution; the other half will receive an intravenous administration of Furosemide Injection.
Detailed description
The prevalence of chronic heart failure is increasing, and despite advances in the treatment of chronic heart failure, in-hospital mortality and readmission are high. Heart failure costs the US about 32 billion per year, and a large percentage of the costs are due to hospitalizations. Most clinicians would agree that patients with decompensated heart failure presenting with hypotension, worsening renal function and altered mental status should be hospitalized. However, there is a subset of patients presenting with dyspnea and edema due to volume overload that necessitate rapid symptom improvement but are hemodynamically stable. Oral diuretics would likely be ineffective but hospital admission for IV diuretics seems excessive. The research hypothesis is that subcutaneously administered furosemide will be an effective alternative to IV furosemide for hemodynamically stable chronic heart failure patients presenting with volume overload in the ambulatory setting. Patients will be randomized to receive Furosemide Injection, USP intravenously or Furosemide Injection Solution (SCP-101) delivered subcutaneously. The IV patients will get the usual care of the heart failure clinic, which includes having an IV placed and delivery of a one-time dose of IV furosemide with the dose determined by the providers (maximum dose 160mg IV). The subcutaneous patients will receive 80mg of Furosemide Injection Solution (SCP-101) administered subcutaneously over 5 hours (30mg in first hour and 12.5mg/hour for 4 hours). Both groups of patients will be observed for 6 hours to assess diuresis. Patients will be asked to fill out a survey about their symptom improvement (Kansas City Cardiomyopathy questionnaire) and overall satisfaction related to the treatment experience. They will also be monitored for side effects including ototoxicity and discomfort at the access site (burning, itching, and pain). Electrolytes and renal function will be checked once after the patients receive diuretic therapy.
Interventions
DRUGFurosemide Injection Solution (SCP-101)
DRUGFurosemide Injection Solution, USP
Sponsors
scPharmaceuticals, Inc.
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities. * Male and female subjects \> 18 years of age * History of at least 3 months treated heart failure (NYHA class II/III/IV), or recent hospitalization for heart failure; presenting to Heart Failure Bridge Clinic (HFBC) with decompensated heart failure symptoms including elevated jugular venous pressure, dyspnea and peripheral edema where the decision is made to give IV diuretics * Able to participate in the study in the opinion of the investigator * Has the ability to understand the requirements of the study and is willing to comply with all study procedures
Exclusion criteria
* Presenting with symptoms where it is anticipated that there is a high chance of hospitalization such as ischemia, uncontrolled arrhythmia, infection, hemodynamic instability (elevated or low blood pressure), respiratory compromise, or electrolyte abnormalities (\>25% increase in creatinine from baseline, potassium, hyponatremia). * On experimental medication or currently participating in a cardiovascular research study. * Presence or need for urinary catheterization, urinary tract abnormality or disorder interfering with urination * Any surgical or medical condition which in the opinion of the investigator may interfere with participation in the study or which may affect the outcome of the study * Inability to comply with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Output | 6-hour period | The volume of urine produced in milliliters over the 6 hours after drug delivery will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart Failure Symptom Scoring/Symptom Improvement | 6-hour period | Will evaluate if subjective heart failure symptoms improve over the period of diuresis. Measured by Kansas City Cardiomyopathy Questionnaire |
| Number of Participants With Side Effects | Up to 6 hours | Cumulative total of pain, local skin reactions (including hematoma and induration) and electrolyte abnormalities. |
| Urine Sodium | 6-hour period | Total urinary sodium produced during the 6 hour urine collection |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Furosemide IV Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment)
Furosemide Injection Solution, USP | 19 |
| Furosemide Subcutaneous (SC) 80 mg dose administered subcutaneously as 30 mg over the first hour and then as 12.5 mg per hour over the subsequent 4 hours (test treatment)
Furosemide Injection Solution (SCP-101) | 21 |
| Total | 40 |
Baseline characteristics
| Characteristic | Total | Furosemide IV | Furosemide Subcutaneous (SC) |
|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 13 | 54 years STANDARD_DEVIATION 13 | 59 years STANDARD_DEVIATION 13 |
| Body mass index | 38.7 kg/m2 STANDARD_DEVIATION 11.2 | 39.7 kg/m2 STANDARD_DEVIATION 11.2 | 37.8 kg/m2 STANDARD_DEVIATION 11.3 |
| Ejection fraction | 25 % left ventricular function | 20 % left ventricular function | 25 % left ventricular function |
| Furosemide daily dose | 246 mg STANDARD_DEVIATION 167 | 228 mg STANDARD_DEVIATION 174 | 261 mg STANDARD_DEVIATION 164 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 14 Participants | 12 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 | 13 Participants | 5 Participants | 8 Participants |
| Region of Enrollment United States | 40 Participants | 19 Participants | 21 Participants |
| Sex: Female, Male Female | 22 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Male | 18 Participants | 10 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 0 / 19 | 1 / 21 |
| serious Total, serious adverse events | 0 / 19 | 0 / 21 |
Outcome results
Primary
Urine Output
The volume of urine produced in milliliters over the 6 hours after drug delivery will be measured.
Time frame: 6-hour period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide IV | Urine Output | 1636 mL | Standard Deviation 875 |
| Furosemide SC | Urine Output | 1515 mL | Standard Deviation 1000 |
Secondary
Heart Failure Symptom Scoring/Symptom Improvement
Will evaluate if subjective heart failure symptoms improve over the period of diuresis. Measured by Kansas City Cardiomyopathy Questionnaire
Time frame: 6-hour period
Population: Data was not collected on enough patients to accurately analyze this endpoint. No data analysis was performed for this outcome.
Secondary
Number of Participants With Side Effects
Cumulative total of pain, local skin reactions (including hematoma and induration) and electrolyte abnormalities.
Time frame: Up to 6 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Furosemide IV | Number of Participants With Side Effects | Hypokalemia | 0 Participants |
| Furosemide IV | Number of Participants With Side Effects | Skin irritation | 0 Participants |
| Furosemide IV | Number of Participants With Side Effects | Infusion site pain | 0 Participants |
| Furosemide SC | Number of Participants With Side Effects | Hypokalemia | 1 Participants |
| Furosemide SC | Number of Participants With Side Effects | Skin irritation | 0 Participants |
| Furosemide SC | Number of Participants With Side Effects | Infusion site pain | 0 Participants |
Secondary
Urine Sodium
Total urinary sodium produced during the 6 hour urine collection
Time frame: 6-hour period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Furosemide IV | Urine Sodium | 7.3 mEq/L | Standard Deviation 35.3 |
| Furosemide SC | Urine Sodium | 32.8 mEq/L | Standard Deviation 43.6 |