Clinical trial NCT02579057: Sub-Q Versus IV Furosemide in Acute Heart Failure
Official title: Prospective, Randomized, Parallel-Group Pilot Study Comparing IV Furosemide to Subcutaneous Furosemide in Acute Decompensated Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Congestive Heart Failure
Keywords: Congestive heart failure
Furosemide
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: scPharmaceuticals, Inc.
First posted: 2015-10-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Urine Output
timeFrame: 6-hour period
Secondary outcomes:
measure: Heart Failure Symptom Scoring/Symptom Improvement
timeFrame: 6-hour period
measure: Number of Participants With Side Effects
timeFrame: Up to 6 hours
measure: Urine Sodium
timeFrame: 6-hour period
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital Heart Failure Bridge Clinic
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Stuart Russell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gilotra NA, Princewill O, Marino B, Okwuosa IS, Chasler J, Almansa J, Cummings A, Rhodes P, Chambers J, Cuomo K, Russell SD. Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure. JACC Heart Fail. 2018 Jan;6(1):65-70. doi: 10.1016/j.jchf.2017.10.001. Epub 2017 Dec 6.