SUBQ-Pilot: Subcutaneous Furosemide in Acute Decompensated Heart Failure Pilot

• Sponsor: Adrian Hernandez (Other)
• Overall Status: Completed
• CT.gov ID: NCT02877095
• Collaborator: (none)
• Enrollment: 40
• Locations: 5
• Arm: 1
• Actual Duration (Months): 10.6
• Patients Per Site: 8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Heart Failure	Drug: Furosemide	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Subcutaneous Furosemide in Acute Decompensated Heart Failure: The SUBQ-HF Pilot Study
• Actual Study Start Date: Dec 19, 2016
• Actual Primary Completion Date: Nov 7, 2017
• Actual Study Completion Date: Nov 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active All subjects in the pilot study will receive the subcutaneous pump to administer a special formulation of furosemide to be delivered subcutaneously.	Drug: Furosemide; subcutaneous furosemide delivered via subcutaneous pump; Other Names: Lasix

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

1. Total anticipated daily IV furosemide dose (at time of screening) >80-200 mg (or equivalent)/day

2. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30322
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Duke University Medical Center	Durham	North Carolina	United States	27705
5	Metro Health System	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• Adrian Hernandez

Investigators

• Principal Investigator: Adrian Hernandez, MD, Duke University
• Study Chair: Eugene Braunwald, MD, Harvard University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 15, 2017

More Information

Publications

None provided.

• Responsible Party: Adrian Hernandez, HFN Coordinating Center PI, Duke University
• ClinicalTrials.gov Identifier: NCT02877095
• Other Study ID Numbers: Pro00070399
• First Posted: Aug 24, 2016
• Last Update Posted: Mar 15, 2019
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Heart Failure; Furosemide

Study Results

Participant Flow

Arm/Group Title	In-patient Pilot	Out-patient Pilot Study
Arm/Group Description	All subjects in the in-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	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
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	In-patient Pilot Study	Out-patient Pilot Study	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	20	20	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.2 (14.6)	57.8 (12.0)	63.0 (14.2)
Sex: Female, Male (Count of Participants)
Female	8 40%	4 20%	12 30%
Male	12 60%	16 80%	28 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 5%	1 2.5%
Not Hispanic or Latino	20 100%	19 95%	39 97.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 30%	4 20%	10 25%
White	14 70%	16 80%	30 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	20 100%	20 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Overall Safety of a Strategy Based on Subcutaneous Delivery of Furosemide in Inpatients and Outpatients as Measured by Number of Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	In-patient Pilot	Out-patient Pilot Study
Arm/Group Description	All subjects in the 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	All subjects in the 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
Measure Participants	20	20
Patients with any Adverse Events	4 20%	9 45%
Patients with no Events	16 80%	11 55%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	In-patient Pilot
	Comments	All subjects on study received active drug.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Total count of events is provided.

Adverse Events

Time Frame	1 year
Arm/Group Title	In-patient Pilot Study		Out-patient Pilot Study
Arm/Group Description	All subjects in the in-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		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
All Cause Mortality
	In-patient Pilot Study		Out-patient Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	In-patient Pilot Study		Out-patient Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		1/20 (5%)
Infections and infestations
Implant site infection	0/20 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	In-patient Pilot Study		Out-patient Pilot Study
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/20 (20%)		8/20 (40%)
Cardiac disorders
Cardiac Failure	0/20 (0%)	0	1/20 (5%)	1
General disorders
Injection Site Pain	2/20 (10%)	2	2/20 (10%)	2
Injection Site discomfort	1/20 (5%)	1	1/20 (5%)	1
Injection site erythema	0/20 (0%)	0	1/20 (5%)	1
Injection site haemorhage	0/20 (0%)	0	1/20 (5%)	1
Injection Site Rash	0/20 (0%)	0	1/20 (5%)	1
Injury, poisoning and procedural complications
Contusion	0/20 (0%)	0	1/20 (5%)	1
Fall	0/20 (0%)	0	1/20 (5%)	1
Procedural haemorrhage	0/20 (0%)	0	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Muscle spasm	0/20 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Nervousness	0/20 (0%)	0	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/20 (5%)	1	0/20 (0%)	0
Dyspnoea	0/20 (0%)	0	1/20 (5%)	1
epistaxis	0/20 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Erythema	0/20 (0%)	0	1/20 (5%)	1
Skin irritation	0/20 (0%)	0	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

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.