An Open Label, Descriptive Study to Evaluate the Clinical Utility of a Novel Formulation of Furosemide Delivered Subcutaneously in Patients Presenting With Early Signs of Fluid Overload
Phase: PHASE2
Conditions: Heart Failure
Sponsor: Steward St. Elizabeth's Medical Center of Boston, Inc.

 
1
St. Elizabeth's Medical Center 
736 Cambridge St, Brighton, MA 02135 
 
CLINICAL PROTOCOL 
 
 
 
 
An Open Label, Descriptive Study to Evaluate the Clinical Utility of a Novel Formulation 
of Furosemide Delivered Subcutaneously in Patients Presenting with Early Signs of Fluid 
Overload 
 
 
 
 
 
 
 
 
 
IND Number:                          Pending 
Protocol Number:  
Version 4.0 
Protocol Date: 
August 30, 2017 
NCT Number 
NCT03359161 
 
 
 
 
 
 
 
Sponsor 
 
St. Elizabeth's Medical Center 
736 Cambridge St, Brighton, MA 02135 
 
 
 
 
 
 
 
 
 
 
 

 
2
 
 
 
Study Sponsor: 
 
      St Elizabeth’s Medical Center 
 
 
 
 
 
 
 
 
 
 
Principal Investigator:                 Lana Tsao. MD 
                                                       St. Elizabeth's Medical Center 
                                                      736 Cambridge St, Brighton, MA 02135 
                                                       Phone: 617-789-3041 
                                                       Email: Lana.Tsao@Steward.org 
 
 
 
Co- Investigator                            Maxwell Eyram Afari, MD 
                                                       St. Elizabeth's Medical Center 
                                                       736 Cambridge St, Brighton, MA 02135 
                                                       Phone: 617-789-3041 
                                                       Email: Maxwell.Afari@Steward.org 
 
 
 
 
 
 
 
 
  
Study Coordinator:  
               Margaret Michaelian 
                                                       St. Elizabeth's Medical Center 
                                                       Cardiovascular Medicine Research Office 
                                                       736 Cambridge St, Brighton, MA 02135 
                                                        617-789-3041           
                                                        margaret.michaelian@steward.org               
 
 
Coordinating Center:  
       Margaret Michaelian 
                                                       St. Elizabeth's Medical Center 
                                                       Cardiovascular Medicine Research Office 
                                                       736 Cambridge St, Brighton, MA 02135 
                                                        617-789-3041 
                                                        margaret.michaelian@steward.org 
 
 
 
 
 
 
 
 
 
 

 
3
 
 
 
 
 
 
INVESTIGATOR PROTOCOL AGREEMENT 
 
Protocol Title: An Open Label, Descriptive Study to Evaluate the Clinical Utility of a Novel 
Formulation of Furosemide Delivered Subcutaneously in Patients Presenting with Early Signs of 
Fluid Overload 
Protocol Number: Version 4.0 
By my signature, I ________________________________________________________ 
 
• agree to conduct the study in accordance with the relevant, current protocol and will only make 
changes in a protocol after notifying the Sponsor, except when necessary to protect the safety, 
rights, or welfare of Subjects.  
• agree to personally conduct or supervise the described investigation(s).  
• agree to inform any patients, or any persons used as controls, that the study product is being 
used for investigational purposes and I will ensure that the requirements relating to obtaining 
informed consent in 21 CFR Part 50 and institutional review board (IRB) review and approval in 
21 CFR Part 56 are met.  
• agree to report to the Sponsor adverse experiences that occur in the course of the 
investigation(s) in accordance with 21 CFR 312.64. I have read and understand the information 
in the Investigator’s brochure, including the potential risks and side effects of the study product.  
• agree to ensure that all associates, colleagues, and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments.  
• agree to maintain adequate and accurate records in accordance with 21 CFR 312.62 and to 
make those records available for inspection in accordance with 21 CFR 312.68.  
• will ensure that an IRB that complies with the requirements of 21 CFR Part 56 will be 
responsible for the initial and continuing review and approval of the clinical investigation. I also 
agree to promptly report to the IRB all changes in the research activity and all unanticipated 
problems involving risks to human subjects or others. Additionally, I will not make any changes 
in the research without IRB approval, except where necessary to eliminate apparent immediate 
hazards to human subjects.  
• agree to comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements in 21 CFR Part 312. 
 
 
Investigator's Signature:                                                                Date 
 
 

 
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Print Name:_________________________________________________________ 
 
Table of Contents 
1 
LIST OF ABBREVIATIONS ............................................................................................... 6 
2 
EXECUTIVE SUMMARY ................................................................................................... 7 
3 
INTRODUCTION ............................................................................................................... 15 
3.1 
BACKGROUND ............................................................................................................ 15 
3.2 
PRELIMINARY DATA ................................................................................................ 15 
4 
OBJECTIVES ...................................................................................................................... 16 
4.1 
PRIMARY OBJECTIVE .............................................. Error! Bookmark not defined.0 
4.2 
SECONDARY OBJECTIVE .......................................... Error! Bookmark not defined. 
5 
OVERALL STUDY DESIGN ............................................................................................ 16 
6 
STUDY POPULATION AND ELIGIBILITY CRITERIA............................................. 17 
6.1 
INCLUSION CRITERIA ............................................................................................... 18 
6.2 
EXCLUSION CRITERIA .............................................................................................. 18 
6.3   REMOVAL OF SUBJECTS FROM THE STUDY ......................................................... 19 
7 
STUDY WORK FLOW ...................................................................................................... 19 
7.1 
Heart Failure Scoring Scale............................................. Error! Bookmark not defined. 
8 
Investigational Product ....................................................................................................... 19 
8.1 
Buffered Furosemide Injection....................................................................................... 20 
8.2 
Labelling......................................................................................................................... 20 
8.3 
Storage and Handling ..................................................................................................... 21 
9 
STUDY EVALUATION ..................................................................................................... 21 
9.1 
Baseline Evaluation ........................................................................................................ 21 
9.2 
Study Days (3 ± 4 days .................................................................................................. 21 
9.3 
Follow Up After Last Treatment .................................................................................... 22 
9.4 
Day 30 Clinic Visit ......................................................................................................... 22 
9.5 
Electrolyte Correction .................................................................................................... 23 
10 OUTCOMES DETERMINATION .................................................................................... 24 
10.1 
Primary Endpoint ........................................................................................................... 24 

 
5
10.2 
Secondary Endpoints ...................................................................................................... 25 
11 RISK MANAGEMENT ...................................................................................................... 25 
12 SUMMARY OF BENEFITS .............................................................................................. 25 
13 PARTICIPANT SAFETY AND ADVERSE EVENTS .................................................... 26 
13.1 
Adverse Events ............................................................................................................... 26 
13.2 
Suspected Adverse Reactions......................................................................................... 26 
13.3 
Serious Adverse Events .................................................................................................. 26 
13.4 
Anticipated Adverse Events and Procedure Effects ....................................................... 26 
13.5 
Device Adverse Events .................................................................................................. 27 
13.6 
Relatedness of AE or SAE to IP..................................................................................... 27 
13.7 
Recording and Reporting of Adverse Events ................................................................. 28 
14 STATISTICAL CONSIDERATIONS ............................................................................... 28 
15 DATA MANAGEMENT PROCEDURES ........................................................................ 29 
16 STUDY ADMINISTRATION ............................................................................................ 29 
17 ETHICAL AND REGULATORY CONSIDERATIONS ................................................ 30 
17.1 
Ethics and Good Clinical Practice .................................................................................. 30 
17.2 
Informed Consent ........................................................................................................... 30 
17.3 
Confidentiality and HIPAA requirements ...................................................................... 30 
17.4 
Institutional Review Board/Independent Ethics Committee .......................................... 30 
18 REFERENCES .................................................................................................................... 31 
19 APPENDICES ..................................................................................................................... 33 
19.1 
Appendix A. Schedule of Assessments .......................................................................... 33 
19.2 
Appendix B. Dyspnea Scale ............................................ Error! Bookmark not defined. 
 
 
 

 
6
1 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACC 
ADHF 
American College of Cardiology 
Acute Decompensated Heart Failure 
AE 
AHA                          
Adverse Event 
American Heart Association 
BMP 
Basic Metabolic Panel 
BUN 
Blood Urea Nitrogen 
CRF 
Case Report Form 
DSMB 
Data Safety Monitoring Board 
eGFR 
Estimated Glomerular Filtration Rate 
ER 
Emergency Room 
FDA 
Food and Drug Administration 
HF 
Heart Failure 
HFpEF 
Heart Failure with preserved Ejection Fraction 
HFrEF 
HIPAA 
Heart Failure with reduced Ejection Fraction 
Health Insurance Portability and Accountability Act 
ICF 
ICH 
Informed Consent Form 
International Conference on Harmonization 
IND 
IP 
Investigational New Drug 
Investigational product 
IRB 
Institutional Review Board 
IV 
 
Intravenous 
NT-proBNP 
SEMC 
SAR 
pro-B-type natriuretic peptide 
St Elizabeth’s Medical Center 
Suspected advanced reactions 
NYHA 
New York Heart Association 
SQ 
Subcutaneous 
 
 

 
7
2 
EXECUTIVE SUMMARY 
SYNOPSIS 
PROTOCOL TITLE 
An Open Label, Descriptive Study to Evaluate the Clinical 
Utility of a Novel Formulation of Furosemide Delivered 
Subcutaneously in Patients Presenting with Early Signs of 
Fluid Overload 
PROTOCOL 
NUMBER 
Version 4.02 
INVESTIGATOR  
Lana Tsao, MD 
Director Advanced Heart Failure Program  
Associate Professor of Medicine, Tufts University School of 
Medicine. 
St. Elizabeth's Medical Center (SEMC) 
736 Cambridge St, Brighton, MA 02135 
INVESTIGATIONAL 
PRODUCT 
Furosemide Injection, 8 mg/mL, (total dose =80 mg) 
administered subcutaneously by the sc2Wear Furosemide 
Infusor using a biphasic profile with 30 mg over the first hour 
and then as 12.5 mg per hour over the subsequent 4 hours. 
Participants may be prescribed a total of 3 days initial treatment 
followed by an optional additional 4 days of sc2Wear 
furosemide treatment based on initial clinical response. 
STUDY 
OBJECTIVES 
 
The Objectives of this study are: 
1.) Evaluate the clinical effect of sc2Wear furosemide Infusor 
in the in-home management of mild to moderate 
decompensated heart failure.  
2.) Evaluate the safety and tolerability of sc2Wear furosemide 
Infusor in the in-home management of mild to moderate 
decompensated heart failure. 
 
STUDY ENDPOINTS 
 
 
Efficacy 
 The treatment effect will be described as: 

 
8
 
• 
% weight loss between enrollment/screening 
compared to Post Visit #1 and Post Visit #2 
• 
Reduction in pro-BNP between 
enrollment/screening compared to Post Visit 
#1 and Post Visit #2 
• 
Proportion of patients requiring additional 4 
days of diuresis based on a set of pre-defined 
criteria. 
• 
% of patients alive 30 days post enrollment  
• 
% of patients without hospitalization for 
worsening HF within 30 days after enrollment 
• 
% of patients without a significant HF related 
medical events within 30 days after 
enrollment. 
 
Safety 
 
 
The safety of the sc2 Wear furosemide Infusor drug-
device combination will be assessed by the incidence of 
adverse events. 
 
Discontinuation due to presence of skin reaction to 
drug or device/adhesive. 
 
STUDY DESIGN & 
DURATION 
 
Study Design: 
This is a prospective, open-label, descriptive two-phase study 
to evaluate the clinical effectiveness of a novel formulation of 
furosemide delivered by subcutaneous administration.  
In the first phase of the study (Pilot Phase) the practicality and 
safety of the novel in-home treatment alternative will be 
evaluated in 20 patients presenting with mild to moderate 
decompensated heart failure to the cardiology service at St 
Elizabeth’s Medical Center (SEMC) at Brighton, 
Massachusetts. 
After completion of the first phase, the representatives of the 
sponsor and scPharmaceuticals will convene to review the 

 
9
experience and results and consider any adjustments to the 
study or workflow before commencing the Evaluation Phase of 
the study in which an additional 40 patients will be recruited.  
The Evaluation Phase may involve participation by other 
Steward Health Care System hospitals.  Adjustments to the 
study procedures are subject to IRB review and approval.    
Participants will be treated daily for 3 consecutive days at 
home after an assessment in the cardiology clinic.  Patients will 
be homebound during the episode of care for decompensated 
heart failure.  Patients will be visited daily by Steward Home 
Care and Hospice for home health nursing services. In the 
evening, participants will have the opportunity to supplement 
diuresis with their usual oral diuretic dose. 
Patients will be evaluated by a cardiologist at SEMC within 24 
hours after the 3rd dose of sc2Wear furosemide.  If a patient 
was found to have satisfactorily responded but requires 
additional parenteral diuretics an additional 4 days may be 
prescribed for a total of 7 consecutive treatments.  
Additionally, up to three sc2Wear furosemide at home 
treatments may be used as authorized by the treating physician 
in case the patient experience worsening of heart failure from 
day 7 to up to 30-days after enrollment. 
Response will be based on the weight loss, decrease in pro-
BNP, or improvement in the dyspnea scale.  If additional units 
are prescribed, patients will be re-evaluated by a cardiologist 
within 24 hours after the last dose of sc2Wear furosemide.  
Participants will require a final follow up with a cardiologist at 
30-33 days after the start of the study for a post treatment 
interview and assessment. 
The protocol is subject to IRB review and approval.   The study 
will be conducted under an Investigator-Initiated 
Investigational New Drug (IND) Application. 
STUDY 
PROCEDURES 
Screening Phase: 
The cardiology service will screen patients with mild to 
moderate fluid overload.  Patients who present with other 
serious or life threatening condition for which hospitalization 
would be indicated are excluded. Women of child bearing 
potential will be screened for pregnancy with a urine pregnancy 

 
10
test.  Eligible participants will be educated on device 
preparation, placement, removal and care in accordance with 
the Instructions of Use Manual.  The screening phase includes 
evaluation of the home situation to ascertain that sufficient 
support is or can be made available for at home treatment as an 
alternative to inpatient care.  In appropriate settings, lay 
caregiver will also be trained.  
 
Pilot Phase. 
 
Patients will be visited daily by Steward Home Care and 
Hospice for home health nursing services in accordance with 
standard procedures. Nursing services will include checking 
vitals, obtaining blood samples and evaluation for clinical 
improvement or worsening.  The first visit will be performed 
within 24 hours after enrollment.   
The first sc2Wear Infusor will be prepared and placed on the 
patient as part of the training.  The patient will go home with 
the sc2Wear furosemide Infusor in place on the abdomen to be 
activated upon arrival at home.  Participants will be treated 
with the sc2Wear furosemide Infusor daily for 3 consecutive 
days at home.  Participants will be evaluated by the cardiology 
service of SEMC within 24 hours after the 3rd dose of sc2Wear 
furosemide.  If a patient was found to have responded 
satisfactorily but requires additional parenteral diuretics an 
additional 4 days may be prescribed for a total of 7 consecutive 
treatments.  If additional units are prescribed patients are to be 
evaluated the cardiology service of SEMC within 24 hours after 
the last dose of sc2Wear furosemide Infusor.   
If the subject requires further parenteral diuresis after the 7 
days of at home treatment, they will be converted to usual care 
at that time, which may require inpatient care.  Participants will 
be instructed to record daily morning weights during and after 
treatment until the second post treatment evaluation.   
Interim clinic visits and laboratory assessments may be 
required based on clinical considerations.    
The following parameters will be studied at Baseline and 
follow-up treatment visits.  

 
11
 
 
Body Weight 
 
Vital signs 
 
HF Physical examination  
 
Dyspnea scale 
 
Routine laboratory panel (incl. electrolyte, pro-BNP)  
 
Adverse events   
 
Injection site assessment  
 
Participants will visit the clinic 30 ± 3 days after the start of the 
study for a post treatment evaluation.  
Evaluation Phase 
The Evaluation Phase mirrors the Pilot Phase except that 
attempts will be made to test pre-defined clinical care paths 
based on the lessons of the Pilot Phase.  Up to two additional 
Steward Health Care sites may participate in the Evaluation 
Phase.    
SC2WEAR 
TREATMENT 
 
Novel Furosemide Injection formulation at neutral pH, 8 
mg/mL, (total dose =80 mg) administered subcutaneously by 
means of the sc2Wear Infusor as 30 mg over the first hour and 
then as 12.5 mg per hour over the subsequent 4 hours. 
Participants will be treated for 3 sequential days with one dose 
of sc2Wear Furosemide Infusor (80mg) daily.  It is generally 
recommended that the sc2Wear infusor be applied in the 
morning.  Oral diuretics should be continued concomitantly 
If a patient was found to have satisfactorily responded but 
requires additional parenteral diuretics an additional 4 days 
may be prescribed for a total of 7 consecutive treatments.   
Additionally, up to three sc2Wear furosemide at home 
treatments may be used as authorized by the treating physician 
in case the patient experience worsening of heart failure from 
day 7 to up to 30-days after enrollment. 
 (Rescue Treatment). 

 
12
NUMBER OF  
SUBJECTS 
60 (20 in Pilot Phase, 40 in Evaluation Phase) 
NUMBER OF SITES 
Pilot Phase: St Elizabeth’s Medical Center 
Evaluation Phase: Up to three hospitals in the Steward Health 
Care System 
PARTICIPATING 
COUNTRIES 
U.S. 
SUBJECT 
POPULATION 
Male and female patients over the age of 18 with mild 
to moderately decompensated heart failure not requiring 
hospital admission for care. Subjects may be enrolled in 
the study only if all inclusion criteria and none of the 
exclusion criteria are met. 
INCLUSION AND 
EXCLUSION 
CRITERIA 
Inclusion Criteria:   
1. Age≥ 18 years   
2. Symptomatic and chronic heart failure (NYHA Class II 
and III). 
3. Patients on guideline directed medical therapy 90 days 
prior to enrollment. 
4. Adequate home environment for at-home treatment. 
5.  Presenting or referred to the ER or clinic because of 
evidence of worsening heart failure with fluid overload 
(decompensation)  
6. A modification in oral diuretics is not clinically 
appropriate as deemed by the investigator.  
7. Estimated excess fluid weight of 4 lbs. or more from 
euvolemic state.  
8. Participant able to give informed consent for 
participation in trial. Agreeing to sign informed consent 
and HIPAA authorization. 
9. Understanding and willing to comply with the protocols 
of the trial.  
10. Ability of the participant or caregiver to independently 
apply the investigational device and medication. 
Exclusion Criteria:  
1. ACC/AHA Stage D heart failure or patients requiring 
IV inotrope therapy 

 
13
2. Massive volume overload (e.g., >20 lbs. of estimated 
fluid weight) or anasarca. 
3. Suspected high risk clinical instability with outpatient 
treatment. 
4. Pregnant females or women of child-bearing age who 
are not willing to use an adequate form of 
contraception. 
5. Chronic Obstructive Pulmonary Disease (COPD) 
moderate or worse:  FEV1/FCV ratio <0.7 and FEV1 
<60 percent predicted. 
6. Rapid atrial fibrillation (AF) (HR >100b/min). 
7. Hypoxia (resting O2 saturation <90%). 
8. Hypotension (systolic blood pressure (SBP) BP < 90 
mmHg). 
9. Uncontrolled diabetes mellitus (DM) (admission 
glucose levels > 300 mg/dL). 
10. Advanced renal disease (eGFR < 30mL/min/1.73m2). 
11. Acute coronary syndrome. 
12. Serum potassium (K+) <3.2 mmol/L or > 5.5mmol/L. 
13. On experimental medication or currently participating 
in an interventional cardiovascular research study, other 
than an observational or registry study. 
14. Having received intravenous furosemide within 24 
hours prior to enrollment. 
15. Urinary tract abnormality or disorder interfering with 
urination 
16. Allergy to the active and inactive ingredients of the 
study medication. 
17. Inability to comply with study requirements.  
18. Dementia. 
19. Ongoing substance abuse. 
20. Concern that the current episode of decompensation 
was precipitated by a serious medical condition which 

 
14
may require additional evaluation or treatment.  
STATISTICAL 
ANALYSIS 
Primary Outcome   
Description of treatment effect and as described in the study 
endpoints.   
Description of the seriousness, severity, relatedness of all 
adverse events observed during the study period.  
 
 
 
1)  

 
15
3 
INTRODUCTION 
3.1 
BACKGROUND 
 
Over 650,000 new heart failure cases are diagnosed annually, and it is estimated that one million 
people get hospitalized per year.1 Readmission rates at 30 days and 6 months are estimated to be 
25% and 50% respectively.  Approximately 5 million people in the United States have symptoms 
or signs of heart failure with a $30 billion annual cost to the US healthcare system.  Hospitals 
across the country have come up with practical and pragmatic strategies to manage acute 
decompensated heart failure (ADHF) in the ambulatory setting due to fiscal incentives.2,3 
The oral bioavailability of furosemide varies from 20% to 90% and in ADHF the absorption of 
furosemide has been found to be  unpredictable.4 It is hypothesized that in ADHF, there is “gut 
edema”, which makes it difficult for the absorption of oral furosemide.  Thus, intravenous 
diuretic therapy has become the cornerstone of the treatment of patients with ADHF.  However, 
intravenous (IV) therapy requires the placement of central or peripheral lines, usually placed and 
managed by health care practitioners.  This is associated with increased maintenance expense, 
associated patient discomfort, and possible line complications.  Also the disposition of patients to 
home as compared to nursing home rehabilitation facilities can be influenced by the type of IV 
line placed.  
 Subcutaneous furosemide has been proposed as an alternative to the delivery of parenteral loop 
diuretics. scPharmaceuticals, Inc (Burlington, MA, USA) has developed a subcutaneous 
formulation of furosemide injection, Furosemide Injection Solution (SCP-101) with a proprietary 
infusion pump for this purpose.  Commercially produced furosemide USP is alkaline, with a pH 
of 8.0 to 9.3, and hence could cause irritation of the subcutaneous tissue.  The proprietary SC 
formulation is the first buffered furosemide injection solution, which is isotonic, and has a 
neutral pH of 7.4.  The sc2Wear™ Furosemide Infusor (scPharmaceutical Inc, Burlington, MA) 
is a two-component design, which combines a reusable component and a cost-effective single-
use cartridge (Figure 1). 
3.2 
PRELIMINARY DATA 
 
The sc2Wear™ Furosemide Infusor is designed to deliver a total of 80mg of parenteral 
furosemide over a period of 5 hours via SC infusion (30mg in hour 1, then 12.5 mg/hour over the 
next 4 hours).  Pivotal pharmacokinetic and pharmacodynamics study evaluating a novel 
formulation of furosemide have shown 99.6% bioavailability with subcutaneous administration 
versus intravenous administration of the current parenteral formulation of furosemide. The 
subcutaneous furosemide formulation was also well tolerated with minimal skin reactions.5 
Subcutaneous infusion of furosemide has similar bioavailability as intravenous therapy with 

 
16
therapeutic levels of furosemide achieved within 30 minutes.6-8  Compared to people who got 
injected with normal saline (control), subcutaneous administration of furosemide was found to 
increase diuresis in normal volunteers.9 
 
 
Figure 1. The sc2Wear™ Furosemide Infusor. 
 
 
 
 
4 
OBJECTIVES  
1) Evaluate the clinical effectiveness of sc2Wear furosemide Infusor in the in-home management 
of mild to moderate decompensated heart failure.  
2.) Evaluate the safety and tolerability of sc2Wear furosemide Infusor in the in-home 
management of mild to moderate decompensated heart failure. 
5 
OVERALL STUDY DESIGN 
 
This is a prospective, open-label, two-phase study to evaluate the clinical utility of subcutaneous 
administration of a novel furosemide formulation.  In the first phase of the study (Pilot Phase), 
the practicality and safety of the novel in-home treatment alternative will be evaluated in 20 
VIAL
VIAL ADAPTER
CARTRIDGE
ACTIVATOR
POWER CORD

 
17
patients presenting with mild to moderate ADHF to the cardiology service at St Elizabeth’s 
Medical Center, Brighton, Massachusetts (SEMC). 
After completion of the first phase, representatives of the sponsor and scPharmaceuticals will 
convene to review the experience and results and consider any adjustments to the study or 
workflow before commencing the Evaluation Phase of the study in which an additional 40 
patients will be recruited.  Adjustments to the study procedures are subject to IRB review and 
approval.  The Evaluation Phase may involve participation by up to three Steward Health Care 
System hospitals. 
Participants will be treated for 3 consecutive days at home.  The sc2Wear™ Furosemide Infusor 
therapy is intended to be performed by the patient or a lay caregiver.  Patients will be 
homebound during the episode of care for decompensated heart failure.  Steward Home Care and 
Hospice will visit patients daily for home health nursing services.  Participants will be visited at 
home by a visiting nurse who will give them further teaching on the sc2Wear™ Furosemide 
Infusor.  The visiting nurse will also be responsible for obtaining history (symptoms), physical 
examination (including inspecting the skin for adverse reactions related to the pump), and 
laboratory draws, supplementation of electrolytes as needed and administration of the dyspnea 
scale.  
Patients will be evaluated by the cardiology service of SEMC within 24 hours of the last dose of 
the sc2Wear™ Furosemide Infusor.  If a patient is found to have satisfactorily responded but 
requires additional parenteral diuretics an additional 4 days may be prescribed for total of seven 
consecutive treatments.  If additional units are prescribed, patients will be evaluated by the 
cardiology service of SEMC within 24 hours of the last dose of the sc2Wear™ Furosemide 
infusion.   
 Additionally, up to three-sc2Wear furosemide at home treatments may be used as authorized by 
the treating physician in case the patient experience worsening of heart failure within 30-days of 
enrollment (Rescue Treatment).  Participants will be seen in clinic for follow up at 30±3 days 
after the start of the study for a post treatment follow up.  A Time and Events Schedule is 
attached as Appendix A. 
 
6 
STUDY POPULATION AND ELIGIBILITY CRITERIA 
The cardiology service at St Elizabeth’s Medical Center will screen patients based on the 
eligibility criteria listed below.  Patients who are deemed to qualify for this therapy will be seen 
at the St Elizabeth’s Medical Center cardiology clinic. 

 
18
6.1 
INCLUSION CRITERIA 
 
 Age≥ 18 years    
 Symptomatic and chronic heart failure (NYHA Class II and III). 
 Patients on guideline directed medical therapy 90 days prior to enrollment. 
 Adequate home environment for at-home treatment. 
 Presenting or referred to the clinic because of evidence of worsening heart failure with 
fluid overload (decompensation).  
 A modification in oral diuretics is not clinically appropriate as deemed by the 
investigator.  
 Estimated excess fluid weight of 4 lbs. or more from euvolemic state.  
 Participant able to give informed consent for participation in trial.  Agreeing to sign 
informed consent and HIPAA authorization. 
 Understanding and willing to comply with the protocols of the trial.  
Ability of the participant or caregiver to independently apply the investigational device and 
medication. 
6.2 
.EXCLUSION CRITERIA 
 
 ACC/AHA Stage D heart failure or patients requiring IV inotrope therapy. 
 Massive volume overload (e.g., >20 lbs. of estimated fluid weight) or anasarca. 
 Suspected high risk clinical instability with outpatient treatment. 
 Pregnant females or women of child-bearing age who are not willing to use an adequate 
form of contraception. 
 Chronic Obstructive Pulmonary Disease (COPD) moderate or worse:  FEV1/FCV ratio 
<0.7 and FEV1 <60 percent predicted. 
 Rapid atrial fibrillation (AF) (HR >100b/min). 
 Hypoxia (resting O2 saturation <90%). 
 Hypotension (systolic blood pressure (SBP) BP < 90 mmHg). 
 Uncontrolled diabetes mellitus (DM) (admission glucose levels > 300 mg/dL). 
 Advanced renal disease (eGFR < 30mL/min/1.73m2). 
 Acute coronary syndrome. 
 Serum potassium (K+) <3.2 mmol/L or > 5.5mmol/L. 
 On experimental medication or currently participating in an interventional cardiovascular 
research study, other than an observational or registry study. 
 Having received intravenous furosemide within 24 hours prior to enrollment. 
 Urinary tract abnormality or disorder interfering with urination. 
 Allergy to the active and inactive ingredients of the study medication. 
 Inability to comply with study requirements.  
 Ongoing substance abuse. 

 
19
 Concern that the current episode of decompensation was precipitated by a serious 
medical condition which may require additional evaluation or treatment. 
 Dementia 
 
6.3   REMOVAL OF SUBJECTS FROM THE STUDY  
All patients who are withdrawn from the study will still need to be monitored closely for 30 days 
for their safety. The following will be reasons to withdraw a participant from the study. 
 
1. Participant request to be withdrawn from the study. 
2. Safety concerns (adverse events or reactions etc.). 
3. Investigator discretion (will usually be related to patient safety). 
4. Treatment failure (the need for a longer parenteral therapy or hospital admission). 
 
7 
STUDY WORK FLOW 
This is a prospective, open-label, two-phase study to evaluate the clinical utility of SQ 
administration of a novel furosemide formulation.  Patients seen in the cardiology clinic who are 
determined to be eligible will be enrolled in this study.   
 
For participants in the trial, during the clinic visit the study investigator, co-investigator who are 
physicians in the cardiology division of SEMC, or a cardiology nurse practitioner will teach the 
participants everything they need to know about the sc2Wear™ Furosemide Infusor. 
scPharmaceuticals will conduct a training session for study staff on the device operation and 
placement and study site will have access to training materials developed by scPharmaceuticals. 
The Pump will be filled and placed on the skin of the upper abdomen in accordance with the 
Instructions for Use Manual (Appendix C ).  The patient will be instructed on how to press the 
activator button to start the administration of the furosemide. When this button is pressed, a 
small needle is deployed automatically to the skin and the furosemide delivery starts.  When the 
medicine has been delivered, the needle pulls back into the Cartridge and then the patient can 
then dispose of the cartridge.  Participants will also be given Quick Reference Guide (QRG 
)(Appendix D) and will be given contact numbers from the cardiology department to call if any 
device troubleshooting questions come up.  Participants will also be provided the technical 
support contact number related to the device. 
8 
Investigational Product 
 
sc2Wear™ Furosemide Infusor delivery system comprises of reusable and disposable 
components. The components are described below. 

 
20
(1) The reusable components which are needed for the drug delivery: 
(a) The Activator consists of the electromotor and pump drive, control electronics, and user 
interface elements (buttons, visual indicators and audible tones), 
(b) A Power Cord for recharging the Activator when not in use, 
 
(2) The Disposable components:  
(a) The drug product: Furosemide Injection Solution (8 mg/mL – total 80 mg in 10 mL), 
provided in a 10mL standard pharmaceutical glass vial,  
(b) An Adapter for accessing the contents of the drug vial, 
(c) A Cartridge that houses the needle and needle insertion mechanism, a micropiston pump, 
drug reservoir and adhesive (for attachment to the body), 
(d) Cavilon No Sting Barrier Film - small wand applicator, 1.0 ml, One applicator wand, for 
protecting the skin. 
(e) Alcohol Prep Pads for cleaning the top of the medicine Vial and the skin prior to applying the 
Pump. 
(f) The device is adhered to the body using medical grade adhesive 1776 acrylate adhesive 
manufactured by 3M.  The 1776 adhesive is identical to the commercially available 3M 
Medipore Tape [Class I, Exempt], except that a liner is added for converting/handling. 
8.1 
 Buffered Furosemide Injection 
Buffered furosemide injection (SCP-101, Furosemide Injection), 10mL of undiluted buffered 
furosemide solution (8 mg/mL), manufactured by Cook Pharmica, Bloomington, IN, USA under 
GMP conditions. Contains Tris Hydrochloride, Sodium Chloride and may contain Sodium 
Hydroxide and Hydrochloric acid for pH adjustment: pH 7.4 (7.0 - 7.8).  The sc2Wear 
furosemide Infusor will be provided by scPharmaceuticals to the investigational site as a starter 
kit (containing the Activator, cartridge and drug) as well as refill kits containing the drug and 
cartridge. 
8.2 
Labeling 
Study drug (Furosemide Injection Solution (SCP-101)) and study device (sc2WearTM 
Furosemide Infusor) will bear labels that meet applicable laws for an investigational drug-device 
combination, which may include, but is not limited to, the following information: 
 Federal law statement 
 Study/Investigator information 
 Batch number  

 
21
 Storage information 
 
8.3 
Storage and Handling 
 
Store study drug at 20° - 25°C, (68° - 77°F), excursions permitted between 15°C and 30°C, 
(between 59°F and 86°F).  Protect from Light. The sc2WearTM Furosemide Combination 
Product must be placed and activated within 7 hours of filling.  Drug delivery must be started 
within 7 hours after filling the device. 
9 
STUDY EVALUATION  
9.1 
Baseline Evaluation  
 
The following information will be obtained from patients who give informed consent.  
 
 Age, sex, past medical history 
 Physical examination 
 Weight, height, Blood pressure, Heart Rate, Respiratory Rate, Temperature  
 NYHA classification 
 Laboratory draws (Sodium, potassium, chloride, Bun, Cr, Mg, pro-BNP, hemoglobin and 
hematocrit) 
 Dyspnea Scale (Appendix B) 
 Current medications 
9.2 
Study Days (3 ± 4 days) 
 
During the study days, patients will be required to continue with their usual evening diuretic 
dose. The following information will be collected by the visiting nurse: 
 
 Weight, Blood pressure, Heart Rate, Respiratory Rate, Temperature  
 Physical exam  
 Injection site inspection 
 Blood draw (Sodium, potassium, chloride, bicarbonate, Bun, Creatine, and Mg)  
 Current Medications 
 Dyspnea scale (Appendix B) 

 
22
 Electrolyte replacement 
 Assessment for adverse events 
9.3 
Follow Up After Last Treatment 
Subjects will be assessed in the office within 24 hours of termination of at home treatment. 
Assessments will include: 
 
 Weight, Blood pressure, Heart Rate, Respiratory Rate, Temperature 
 Physical examination 
 NYHA classification  
 Injection site assessment  
 Blood test (Sodium, chloride, potassium, bicarbonate, Bun, Creatine, magnesium, pro 
BNP) 
 Dyspnea scale (appendix B)  
 Assessment for adverse events 
 Assessment for interval hospitalizations, ED visits, or unscheduled clinic visits 
 
At this visit, the physician can decide if the treatment should be extended for four extra days 
(after the initial three days of therapy).  If there is no interval improvement, the physician can 
withdraw the subjects from the trial for safety reasons. The initial follow up assessment will be 
included in the final analysis. Patients who show improvement with initial treatment ( 3 days or 3 
day plus up to 4 days at home) may be offered 3 extra days of “rescue treatment” as needed 
within 30 days of enrollment in the trial.  During the “rescue treatment” they will be evaluated 
daily by the visiting nurse and at follow up if they need further assessment as done during the 
treatment phase. 
9.4 
   Day 30 ± 3 Clinic Visit 
 
At Day 30, study follow-up (+/- 3 days). Subjects will undergo the following assessment. 
 
 Medical history 
 Physical examination 
 Weight, Blood pressure, Heart Rate, Respiratory Rate, Temperature  
 NYHA classification 

 
23
 Injection site inspection 
 Blood draw (sodium, potassium, chloride, bicarbonate, Bun, Creatine, magnesium, pro-
BNP 
 Current Medications  
 Assessment for interval hospitalizations, ED visits, or unscheduled clinic visits 
 Assessment for adverse events  
 Dyspnea Scale (Appendix B) 
 
Visiting Nursing Timeline 
A week prior to the initiating of the study, the visiting nurses will be given an orientation and 
will be taught how to use the sc2Wear Furosemide Infusor. They will also be trained on how to 
use the dyspnea scale to ensure consistency of the results.  
The visiting nurse will visit the participant at home within 24 hours of starting the treatment. 
These visits will occur on the three treatment days and an additional 4 days if it is determined 
that the participant needs extra days. Also participants who need an extra three days of rescue 
treatment during 30 days will be seen on consecutive days by the visiting nurse.  
 
 
9.5 
Electrolyte Correction 
 
At the clinic, prior to the start of therapy –a basic metabolic panel, pro-BNP, hemoglobin and 
hematocrit, and magnesium level will be drawn STAT to ensure that the results are back within 2 
hours. Electrolytes will be replenished in accordance with established protocols (Tables 1 and 2) 
10.  The same protocol will be utilized for electrolyte imbalances correction during the follow up 
visits by the visiting home nurse. 
 
. 
 
Serum Creatinine 
(mg/dL) 
Serum Potassium Level (mEq/L) 
< 3.1 
3.1-3.3 
3.4-3.6 
3.7-4.0 
> 4.0 
< 2.0 
40 mEq 
then 
40 mEq 
40 mEq 
then 
20 mEq 
40 mEq 
20 mEq 
- 
2.0-2.8 
40 mEq 
then 
20 mEq 
then 
20 mEq 
- 
- 

 
24
20 mEq 
10 mEq 
> 2.8 
30 mEq 
20 mEq 
10 mEq 
- 
- 
* If the serum potassium is < 3 mEq/L or > 5.5 mEq/L, additional monitoring should occur 
within 24 hours. 
 
 
 
Serum Creatinine 
(mg/dL) 
Magnesium Level (mEq/L) 
< 1.0 
1.0-1.5 
1.6-1.9 
> 1.9 
< 2.0 
3 gm 
2 gm 
1 gm 
- 
≥ 2.0 
2 gm 
1 gm 
- 
- 
 
 
 
10 OUTCOMES DETERMINATION 
10.1 Efficacy Endpoints 
 
• 
% weight loss between enrollment/screening compared to Post Visit #1 and 
Post Visit #2 
• 
Reduction in pro-BNP between enrollment/screening compared to Post Visit #1 
and Post Visit #2 
• 
Proportion of patients requiring additional 4 days of diuresis.. 
• 
Percentage of patients alive 30 days post enrollment  
• 
Percentage of patients without hospitalization for worsening HF within 30 days 
after enrollment.  
• 
Percentage of patients without a significant HF related medical event within 30 
days after enrollment. 

 
25
10.2 Safety Endpoints 
 
 
The safety of the sc2 Wear furosemide drug-device combination will be assessed by the 
incidence of adverse events. 
 
Discontinuation due to presence of skin reaction to drug or device/adhesive. 
 
11 RISK MANAGEMENT  
 
Furosemide has been available for over five decades and is considered a safe drug.  The potential 
risks related to this study are not different from the risks of any form of diuresis whether 
inpatient or outpatient.  During diuresis, sometimes there are rapid fluid shifts which could lead 
to electrolyte imbalance or postural hypotension.  Subjects will be closely monitored and 
electrolytes will be supplemented as needed.  Patients will be encouraged to avoid rapid postural 
changes during diuresis and will need to be homebound to ensure their safety. 
Patients will be informed of the expected increased urine output. Rarely gout may also be 
precipitated when fluid is taken out of the body.  Dryness of the mouth, thirst, weakness, 
lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, 
oliguria, tachycardia, arrhythmia, or gastrointestinal disturbances such as nausea and vomiting 
will be monitored. There are rare risks of local allergic reaction from the adhesive of the infusor, 
activation of systemic lupus erythematosus or worsening kidney function in which case the SQ 
furosemide infusion will be stopped.  Patients allergic to sulfa may be allergic to furosemide. 
Patients with diabetes mellitus should be told that furosemide may increase blood glucose levels 
and thereby affect urine glucose tests.  The skin of some patients may be more sensitive to the 
effects of sunlight while taking furosemide.  Patients may not participate in this study if they are 
pregnant or plan to be pregnant during the study since the effects of the study device system on 
an unborn baby are unknown. 
12 SUMMARY OF BENEFITS 
 
It is anticipated that patients will experience clinical improvement of the symptoms and signs of 
HF. Participants will also avoid the cost related to being admitted to the hospital for intravenous 
furosemide infusion.  

 
26
13 PARTICIPANT SAFETY AND ADVERSE EVENTS 
Adverse Events 
 
An adverse event (AE) is any unfavorable or unintended medical occurrence associated with the 
use of an investigational product (IP).  This does not necessarily imply causality. 
Pre-existing conditions would be reported as AEs if the frequency, intensity, or character of the 
pre-existing condition worsens during the course of the study.  Conditions detected after use of 
the IP are AE, though they might have prior existence.  Laboratory or functional test 
abnormalities that meet the criteria for AEs are those that are associated with clinical signs or 
those whose clinical symptoms require medical intervention, and or which require the IP to be 
discontinued.  When the patient withdraws from the study 
13.1    Suspected Adverse Reactions 
A suspected adverse reaction (SAR) refers to events which could have been possibly caused by 
the drug.  Adverse reactions, a subset of SAE, indicates a higher certainty (that event was caused 
by IP). 
 
13.2 Serious Adverse Events 
Serious Adverse Event (SAE) refers to any event that result in the following 
 
 Death 
 Life-threatening AE 
 A disability or incapacity 
 Inpatient hospitalization due to the therapy. This may not include patients who choose to 
withdraw from the study and opt to be admitted or patients who are withdrawn from the 
study for better diuresis in the hospital. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions. 
 Congenital anomaly or birth defect of an offspring 
13.3  Anticipated Adverse Events and Procedure Effects 
 
These refer to AEs related to acute heart failure. 
 Acute coronary syndrome (unstable angina, non ST elevation myocardial infarction, ST 
elevation myocardial infarct) 
 Arrhythmias and sudden cardiac death 
 Venous thrombosis 

 
27
 Cerebrovascular events (stroke or transient ischemic attacks) 
 Worsening heart failure or heart failure refractory to therapy requiring inotropes or 
mechanical support 
 Presyncope and syncope 
 Acute kidney injury defined as a rise in creatinine > 0.3 mg/dL over 48 hours, or 
progressive loss of renal function over time. 
 
13.4 Device Adverse Events 
 
If the pump falls off during drug infusion or if the needle appears before pump placement there is 
a risk of needle stick.  In this scenario, the pump will need to be handled carefully.  Device 
adverse reactions could include local reaction/skin irritation or redness, allergic reaction to the 
adhesive agent, and rarely scarring. 
 
 
13.5 Pre Specified Adverse Events 
 
Hyperkalemia defined as K > 5.5 meq/L 
Hypokalemia, defined as K<3.0 meq/ml 
Hypomagnesemia, defined as Mg < 1.5 mg/dl 
Worsening kidney function (50% increase in baseline creatinine level) 
13.6  Relatedness of AE or SAE to IP  
 
Using his/her best medical judgment and the available information on the Investigational Product 
(IP), the Investigator will determine if the AE and or SAE caused the observed symptoms 
associated with the event. 
 
 Not related: Unestablished reasonable causal relationship between the IP and the AE.  
 Unlikely related: No temporal association or cause of the event has been identified. 
 Possibly related: There is reasonable evidence to suggest a causal relationship between 
the drug and adverse event, however there could be other confounders to the AE 
 .Related: There is a causal relationship 
13.7 Severity of AEs 
 
  The severity of AEs should be documented using the following criteria. 

 
28
 
• 
Mild: symptom does not influence performance. Subject barely notices it 
• 
Moderate: Subject’s daily performance is affected. Treatment may be needed. 
• 
Severe: Subject experiences severe discomfort. Treatment necessary 
13.8 Outcome of AEs 
 
One of the following outcomes should be documented 
 Not resolved: symptom No improvement 
 Resolved: Symptoms have improved. 
 Resolved with sequelae: Improvement of AE but has retained a pathological condition 
related to the event. 
 Unknown: Subject refused further contact, not known  Fatal: Death as a result of AE 
 
13.9  Recording and Reporting of Adverse Events 
 
At follow up visits or when visited by the Visiting nurse, participants should be asked non-
leading questions such as “Have you had any issues lately”, “How do you feel”, “Have you made 
any changes to your medications recently” and “have you had any medical problems that I 
should know of”.  The principal investigator will be notified promptly of any AE or SAEs within 
24 hours of the event. 
All AE and SAE’s should be promptly documented with Subject ID, the serious adverse event 
term, onset date, relationship to study product, and a brief narrative of the event.  The 
investigator must promptly determine the relationship to study product or causality.  Events 
should be recorded on the Case Report Forms attached as Appendix F. The Investigator should 
make the SAEs available to the IRB.  Any AE or SAE occurring within 30 days of completion of 
the study should be reported. 
14 STATISTICAL CONSIDERATIONS 
 
An open label, descriptive study to evaluate the clinical utility of a novel formulation of 
furosemide delivered subcutaneously in patients early signs of fluid overload. Binary variables 
will be presented as percentages; Gaussian continuous variables will be presented as mean ± 
standard deviation (SD), while non-Gaussian continuous variables could be presented as median 
with interquartile range (IQR). There will be no head-to-head comparison of the participants of 
the study however the study is expected to provide valuable information on the efficacy of this 
therapy as measured by the primary endpoints which include percentage weight loss, reduction in 
pro-BNP, re-admission, percentage with extended treatment,  percentage of patients with heart 

 
29
failure related adverse events and survival at 30 days.  As already outlined, safety will be 
reported based on the incidence of the adverse events and percentage of subjects with skin 
reaction requiring discontinuation. Data will be analyzed for the initial 20 patients in the pilot 
phase. At the end of the trial, all the 60 subjects (combined pilot and maintenance phase would 
be analyzed together). A study with 59 evaluable subjects has the power to detect with 95% 
confidence the presence of events with an incidence of 5% or greater.  Failure of such material 
event to occur in a study with 59 evaluable patients indicates that the incidence of such event is 
less than 5%.     
 
15 DATA MANAGEMENT PROCEDURES 
 
Clinical study data will be saved on a password protected dedicated drive used for research 
purposes at the St Elizabeth Medical Center.  Home visits by the visiting nurse and clinic visits 
will be documented on the provided CRF (attached as Appendix G).  Participant file will have 
the following documents related to the patient such as the following (but not limited to):  
clinician and nurse’s notes, laboratory and imaging reports, screening and enrollment log etc.  
The Investigator’s study file will contain the informed consent, protocol/ amendments, CRF, and 
other appropriate documents and correspondence such as with the IRB and the FDA. 
The investigator will endeavor to retain clinical study records for at least two years after the last 
approval of a marketing application in an ICH region; or, until two years after the IND is 
discontinued and regulatory authorities have been notified.  scPharmaceuticals will be notified 
prior to destroying any clinical study records. 
 
16 STUDY ADMINISTRATION 
 
The Principal Investigator agrees by her participation that the results of this study may be used 
for submission to national and/or international registration and supervising authorities.  If 
required, these authorities will be provided with the name of the Principal Investigator, their 
addresses, qualifications and extent of involvement.  It is understood that the Principal 
Investigator is required to provide scPharmaceuticals with all study data, complete reports, and 
access to all study records.  The sc2Wear™ Furosemide Infusor will be returned to 
scPharmaceuticals at the completion of the study. 
Data generated by this study must be available for inspection by the US FDA and other 
regulatory authorities, by scPharmaceuticals and its designees, and the IRB as appropriate.  At a 
Subject’s request, medical information may be given to his or her personal physician or other 
appropriate medical personnel responsible for his or her welfare.  Subject medical information 

 
30
obtained during the course of this study is confidential and disclosure to third parties other than 
those noted above is prohibited. 
 
17 ETHICAL AND REGULATORY CONSIDERATIONS 
17.1 Ethics and Good Clinical Practice 
By signing this protocol, the investigator will ensure adherence to the protocol and to Good 
Clinical Practice as stated in the following documents.  
1. The principles of the “Declaration of Helsinki”  
2. ICH Harmonized Tripartite Guidelines for Good Clinical Practice 1996. 
3. US 21 Code of Federal Regulations dealing with clinical studies (including parts 312 (IND 
regulations), 54 (financial disclosure), 50 (informed consent) and 56 (IRB regulations). 
17.2 Informed Consent 
 
A written informed consent will be obtained from all participants prior to enrolling in the study. 
This consent , which is attached as appendix F, will be obtained by the Principal Investigator or 
designee  A copy of the signed consent form will be provided to the Subject 
17.3 Confidentiality and HIPAA requirements 
 
Confidentially will be maintained for all the information collected on study participants per the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA; Pub.L. 104–191, 110 Stat. 
1936). Only authorized personnel will have access to subject information collected as part of this 
study. 
17.4 Institutional Review Board/Independent Ethics Committee 
 
This study will only be started when the Institutional Review Board (IRB) approves the 
protocol. All amendments to the protocol are subject to IRB review and approval 
17.5 Monitoring 
.  
The study will be monitored by the Principal Investigator to ensure compliance to the study 
protocol, verify the signing of informed consent by the subjects, and assist the study personnel with 

 
31
any questions related to the study. Also an institution designated person will have direct access to 
the study data, informed consent and CRF to ensure consistency and accuracy in data gathering. 
This designee will have direct access to the Investigator’s source documentation in accordance 
with International Conference on Harmonization Good Clinical Practice (ICH-GCP). 
 
18 REFERENCES 
 
1. 
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, 
Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, 
Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER, 3rd, 
Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey 
DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, 
Woo D, Yeh RW, Turner MB, American Heart Association Statistics C and Stroke Statistics S. 
Heart disease and stroke statistics--2015 update: a report from the American Heart Association. 
Circulation. 2015;131:e29-322. 
2. 
Ryder M, Murphy NF, McCaffrey D, O'Loughlin C, Ledwidge M and McDonald K. 
Outpatient intravenous diuretic therapy; potential for marked reduction in hospitalisations for 
acute decompensated heart failure. Eur J Heart Fail. 2008;10:267-72. 
3. 
Lazkani M and Ota KS. The role of outpatient intravenous diuretic therapy in a transitional 
care program for patients with heart failure: a case series. J Clin Med Res. 2012;4:434-8. 
4. 
Vasko MR, Cartwright DB, Knochel JP, Nixon JV and Brater DC. Furosemide absorption 
altered in decompensated congestive heart failure. Annals of internal medicine. 1985;102:314-8. 
5. 
Ojeifo OR, S.;Okwuosa,I. Subcutaneous Versus Intravenous Furosemide in the Johns 
Hopkins Heart Failure Bridge Clinic. J Card Fail. 2016;22:S81. 
6. 
Goenaga MA, Millet M, Sanchez E, Garde C, Carrera JA and Arzellus E. Subcutaneous 
furosemide. Ann Pharmacother. 2004;38:1751. 
7. 
Sica DM, P.;DeBoer,R. Pharmacokinetic and Pharmacodynamic Response after 
Subcutaneous Administration of a Novel Furosemide Formulation. J Card Fail. 2016;22:S11. 
8. 
Zatarain-Nicolas E, Lopez-Diaz J, de la Fuente-Galan L, Garcia-Pardo H, Recio-Platero A 
and San Roman-Calvar JA. Subcutaneous infusion of furosemide administered by elastomeric 
pumps for decompensated heart failure treatment: initial experience. Rev Esp Cardiol (Engl Ed). 
2013;66:1002-4. 
9. 
Verma AK, da Silva JH and Kuhl DR. Diuretic effects of subcutaneous furosemide in 
human volunteers: a randomized pilot study. Ann Pharmacother. 2004;38:544-9. 
10. Buckley LF, Carter DM, Matta L, Cheng JW, Stevens C, Belenkiy RM, Burpee LJ, Young 

 
32
MA, Weiffenbach CS, Smallwood JA, Stevenson LW and Desai AS. Intravenous Diuretic 
Therapy for the Management of Heart Failure and Volume Overload in a Multidisciplinary 
Outpatient Unit. JACC Heart Fail. 2016;4:1-8. 
 

 
33
19 APPENDICES 
Appendix A. Schedule of Assessments 
 
 
Screening Baseline 
Treatment*  
First Post 
Treatment 
Second Post 
Treatment 
(if 
applicable) 
Post-
Treatment 
Visit  
Day 
0 
0 
Daily (3 ± 4 
days) 
 
Within 24hrs 
of last 
treatment 
Within 24hrs 
of last 
treatment 
30±3days 
after first 
dose 
Informed 
Consent 
X 
 
 
 
 
 
Pregnancy 
Test* 
X 
 
 
 
 
 
Training 
 
X 
 
 
 
 
Medical 
History 
 
X 
 
 
 
 
Initial sc2Wear 
Treatment 
 
X 
 
 
 
 
Weight 
 
X 
X 
X 
X 
X 
Height 
 
X 
 
 
 
 
HF Physical 
Exam 
 
X 
X 
X 
X 
X 
NYHA 
 
X 
 
X 
X 
X 
Baseline Labsa 
 
X 
 
 
 
 
Monitoring 
labsb 
 
 
X 
X 
X 
X 
Vitals Signsc 
 
X 
X 
X 
X 
X 
Dyspnea Scale 
 
X 
X 
X 
X 
X 
Electrolyte 
correction  
 
X 
X 
 
 
 
Injection Site 
Inspection 
 
 
X 
X 
X 
X 
Current 
Medication 
X 
X 
 
 
X 
X 
X 
X 
Adverse 
Events d  
 
X 
X 
X 
X 
X 

 
34
 
* To be performed by Steward Home Care and Hospice in accordance with standard practices for 
homebound heart failure patients 
a. Baseline laboratory panel (Sodium, potassium, Bun, Cr, Mg, pro-BNP, Hemoglobin and 
Hematocrit) 
b. Monitoring laboratory panel: (sodium, chloride, bicarbonate, potassium, Bun, Cr, Mg) 
c. Vital signs: Blood pressure, heart rate, temperature, respiratory rate 
d. Adverse Events: Major Event: death, hospitalization, MACE (major adverse cardiac event); 
Minor: ER visit for acute decompensated heart failure (excluding study related visits), 
admission to SNF or similar inpatient facility 
 
 
Appendix B: Modified Medical Research Council Dyspnea Scale 
 
 
 
 
 
Appendix C: Instructions for Use Manual 
 
Appendix D. Quick Reference Guide (QRG) 
 
Appendix E: Informed Consent Form 
 
Appendix F: Case Report Form (Adverse Events) 
 
Appendix G: Case Report Form (Home Visits) 
 
 
 
Score 
Modified Medical Research Council Scale 
0 
 I only get breathless with strenuous exercise.  
1 
I get short of breath when hurrying on level ground or walking up a slight hill.  
2 
 On level ground, I walk slower than people of the same age because of breathlessness 
or have to stop for breath when walking at my own pace.  
3 
 I stop for breath after walking about 100 yards or after a few minutes on level ground.  
4 
 I am too breathless to leave the house or I am breathless when dressing