Sub-Q Versus IV Furosemide in Acute Heart Failure

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02579057
• Collaborator: scPharmaceuticals, Inc. (Industry)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 17
• Patients Per Site Per Month: 2.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure	Drug: Furosemide Injection Solution (SCP-101); Drug: Furosemide Injection Solution, USP	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Prospective, Randomized, Parallel-Group Pilot Study Comparing IV Furosemide to Subcutaneous Furosemide in Acute Decompensated Heart Failure Patients
• Actual Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Furosemide Injection Solution, USP Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment)	Drug: Furosemide Injection Solution, USP; Other Names: IV furosemide
Experimental: Furosemide Injection Solution (SCP-101) 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)	Drug: Furosemide Injection Solution (SCP-101); Other Names: sc Furosemide

Outcome Measures

Primary Outcome Measures

1. Urine Output [6-hour period]

   The volume of urine produced in milliliters over the 6 hours after drug delivery will be measured.

Secondary Outcome Measures

1. 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

2. Number of Participants With Side Effects [Up to 6 hours]

   Cumulative total of pain, local skin reactions (including hematoma and induration) and electrolyte abnormalities.

3. Urine Sodium [6-hour period]

   Total urinary sodium produced during the 6 hour urine collection

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital Heart Failure Bridge Clinic	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University
• scPharmaceuticals, Inc.

Investigators

• Principal Investigator: Stuart Russell, MD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 5, 2015

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02579057
• Other Study ID Numbers: IRB00068019
• First Posted: Oct 19, 2015
• Last Update Posted: Dec 18, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Johns Hopkins University: Congestive heart failure; Furosemide
• Additional relevant MeSH terms: Heart Failure; Furosemide; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Furosemide IV	Furosemide Subcutaneous (SC)
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, United States Pharmacopeia (USP)	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)
Period Title: Overall Study
STARTED	19	21
COMPLETED	19	21
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Furosemide IV	Furosemide Subcutaneous (SC)	Total
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP	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)	Total of all reporting groups
Overall Participants	19	21	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (13)	59 (13)	57 (13)
Sex: Female, Male (Count of Participants)
Female	9 47.4%	13 61.9%	22 55%
Male	10 52.6%	8 38.1%	18 45%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4.8%	1 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	14 73.7%	12 57.1%	26 65%
White	5 26.3%	8 38.1%	13 32.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	19 100%	21 100%	40 100%
Body mass index (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	39.7 (11.2)	37.8 (11.3)	38.7 (11.2)
Ejection fraction (% left ventricular function) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [% left ventricular function]	20	25	25
Furosemide daily dose (mg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg]	228 (174)	261 (164)	246 (167)

Outcome Measures

1. Primary Outcome

Title	Urine Output
Description	The volume of urine produced in milliliters over the 6 hours after drug delivery will be measured.
Time Frame	6-hour period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide IV	Furosemide SC
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP	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)
Measure Participants	19	21
Mean (Standard Deviation) [mL]	1636 (875)	1515 (1000)

2. Secondary Outcome

Title	Heart Failure Symptom Scoring/Symptom Improvement
Description	Will evaluate if subjective heart failure symptoms improve over the period of diuresis. Measured by Kansas City Cardiomyopathy Questionnaire
Time Frame	6-hour period

Outcome Measure Data

Analysis Population Description

Data was not collected on enough patients to accurately analyze this endpoint. No data analysis was performed for this outcome.

Arm/Group Title	Furosemide IV	Furosemide SC
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP	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)
Measure Participants	0	0

3. Secondary Outcome

Title	Number of Participants With Side Effects
Description	Cumulative total of pain, local skin reactions (including hematoma and induration) and electrolyte abnormalities.
Time Frame	Up to 6 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide IV	Furosemide SC
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP	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)
Measure Participants	19	21
Hypokalemia	0 0%	1 4.8%
Skin irritation	0 0%	0 0%
Infusion site pain	0 0%	0 0%

4. Secondary Outcome

Title	Urine Sodium
Description	Total urinary sodium produced during the 6 hour urine collection
Time Frame	6-hour period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Furosemide IV	Furosemide SC
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP	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)
Measure Participants	19	21
Mean (Standard Deviation) [mEq/L]	7.3 (35.3)	32.8 (43.6)

Adverse Events

Time Frame	1 month
Arm/Group Title	Furosemide IV		Furosemide Subcutaneous (SC)
Arm/Group Description	Single dose determined by Investigator (maximum dose 160mg) administered intravenously by IV bolus over approximately 2 minutes (reference treatment) Furosemide Injection Solution, USP		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)
All Cause Mortality
	Furosemide IV		Furosemide Subcutaneous (SC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Serious Adverse Events
	Furosemide IV		Furosemide Subcutaneous (SC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Furosemide IV		Furosemide Subcutaneous (SC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		1/21 (4.8%)
General disorders
Hypokalemia	0/19 (0%)	0	1/21 (4.8%)	1

Limitations/Caveats

This was a phase II exploratory trial with a small sample size

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.